Ingenious Synergy of a Pathology-Specific Biomimetic Multifunctional Nanoplatform for Targeted Therapy in Rheumatoid Arthritis.

Based on the pathological characteristics of rheumatoid arthritis, including the overproduction of reactive oxygen species (ROS), inflammatory responses, and osteoclast differentiation, a biomimetic multifunctional nanomedicine (M-M@I) is designed. Iguratimod (IGU) is loaded, which inhibits inflammatory responses and osteoclast differentiation, into mesoporous polydopamine (MPDA), which scavenges ROS. Subsequently, the nanoparticles are coated with a cell membrane of macrophages to achieve actively targeted delivery of the nanoparticles to inflamed joints. It is shown that the M-M@I nanoparticles are taken up well by lipopolysaccharide-induced RAW 264.7 macrophages or bone marrow-derived macrophages (BMDMs). In vitro, the M-M@I nanoparticles effectively scavenge ROS, downregulate genes related to inflammation promotion and osteoclast differentiation, and reduce the proinflammatory cytokines and osteoclast-related enzymes. They also reduce the polarization of macrophages to a pro-inflammatory M1 phenotype and inhibit differentiation into osteoclasts. In mice with collagen-induced arthritis, the M-M@I nanoparticles accumulate at arthritic sites and circulate longer, significantly mitigating arthritis symptoms and bone destruction. These results suggest that the pathology-specific biomimetic multifunctional nanoparticles are effective against rheumatoid arthritis, and they validate the approach of developing multifunctional therapies that target various pathological processes simultaneously.

Drug-Embedded Nanovesicles Assembled from Peptide-Decorated Hyaluronic Acid for Rheumatoid Arthritis Synergistic Therapy.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes endless pain and poor quality of life in patients. Usage of a lubricant combined with anti-inflammatory therapy is considered a reasonable and effective approach for the treatment of RA. Herein, inspired by glycopeptides, a peptide-decorated hyaluronic acid was synthesized, and the grafted Fmoc-phenylalanine-phenylalanine-COOH (FmocFF) peptide self-assembled with ß-sheet conformations could induce the folding of polymer molecular chains to form a vesicle structure in aqueous solution. The hydrophobic anti-inflammatory drug curcumin (Cur) could be embedded in the vesicle walls through π-π interactions with the FmocFF peptide. Furthermore, the inflammation suppression function of the Cur-loaded vesicles both in vitro and in vivo was demonstrated to be an effective treatment for RA therapy. This work proposes new insights into the folding and hierarchical assembly of glycopeptide mimics, providing an efficient approach for constructing intelligent platforms for drug delivery, disease therapy, and diagnostic applications.

Tourniquets can further reduce perioperative blood loss in patients on dexamethasone and tranexamic acid during cemented total knee arthritis: a single-center, double-blind, randomized controlled trial.

BACKGROUND: Multiple doses of dexamethasone and tranexamic acid can inhibit postoperative inflammation and reduce fibrinolysis and perioperative blood loss in total knee arthroplasty. In this single-center, double-blind, randomized clinical trial, the aim was to investigate whether applying a tourniquet to patients on dexamethasone and tranexamic acid could further reduce perioperative blood loss. MATERIALS AND METHODS: Patients who underwent cemented total knee arthroplasty at our hospital were randomized to receive a tourniquet (n = 71) or not (n = 70) during the procedure. All patients received multiple doses of dexamethasone and tranexamic acid perioperatively. The primary outcome was perioperative blood loss, while secondary outcomes were surgery duration, postoperative laboratory indices of inflammation and fibrinolysis, range of knee motion, VAS pain score, knee circumference, knee swelling rate, homologous transfusion, albumin use, and complications. RESULTS: Using a tourniquet was associated with significantly lower intraoperative blood loss (P < 0.001) and total blood loss (P = 0.007) as well as significantly shorter surgery duration (P < 0.001). In contrast, the tourniquet did not significantly affect hidden blood loss, postoperative inflammation or fibrinolysis, range of knee motion, VAS pain score, knee circumference, knee swelling rate, homologous transfusion, albumin use, or complications. CONCLUSIONS: The results of this randomized clinical trial demonstrate that applying a tourniquet during cemented total knee arthroplasty to patients receiving multiple doses of dexamethasone and tranexamic acid can further reduce perioperative blood loss without increasing the risk of inflammation, fibrinolysis, or other complications. Thus, it is advised to use tourniquets combined with dexamethasone and tranexamic acid to reduce perioperative blood loss and avoid tourniquet-related adverse events. LEVEL OF EVIDENCE: Therapeutic Level I. Trial registration Chinese Clinical Trail Registry, ChiCTR2200060567. Registered 5 June 2022-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=171291.

Wound complications and bleeding with new oral anticoagulants in patients undergoing total joint arthroplasty: A systematic review and meta-analysis of randomized controlled trials.

AIMS: The results of associations between new oral anticoagulants (NOACs) and wound complications after total joint arthroplasty remain inconsistent. We conducted a systematic review and meta-analysis of randomized controlled trials to make comparisons with low molecular weight heparins (LMWH) on the clinical outcomes of total wound complications, together with other efficacy and safety endpoints to further evaluate the safety and efficacy of NOACs. METHODS: This meta-analysis was conducted based on a published protocol (PROSPERO: CRD42019140841). We searched for available articles in PubMed, Embase and Cochrane Library through Jun 62 021. Random-effects meta-analyses, including subgroup analyses, were conducted to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for specific doses of NOACs. RESULTS: We retrieved 1683 studies, of which 20 were eligible for inclusion. We found that apixaban was associated with a lower incidence of total wound complications compared with LMWH (RR = 0.81; 95% CI: 0.65-1.00), while dabigatran and rivaroxaban did not increase the risk of total wound complications. In addition, apixaban was associated with a reduction in the risk of major/clinically relevant nonmajor bleeding events compared to LMWH (RR = 0.80, 95% CI: 0.65-0.99), while rivaroxaban increased the risk for major/clinically relevant nonmajor bleeding events (RR = 1.23, 95% CI: 1.02-1.50). Moreover, all 4 NOACs were associated with lower incidences of major venous thromboembolism compared with LMWH. CONCLUSION: A lower risk of wound complications was detected for apixaban, while dabigatran and rivaroxaban did not increase the risk when compared with LMWH. The efficacy of 4 NOACs was broadly similar.

Plasma fibrinogen: a sensitive biomarker for the screening of periprosthetic joint infection in patients undergoing re-revision arthroplasty.

BACKGROUND: Although serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), plasma fibrinogen and neutrophil-lymphocyte ratio (NLR) are promising biomarkers for screening PJI in patients undergoing revision arthroplasty, their efficacy with respect to re-revision arthroplasty remains unclear. METHODS: We included patients who underwent re-revision arthroplasty at our hospital during 2008-2020, and stratified them into two groups whether they had been diagnosed with PJI (infected) or aseptic failure (non-infected) according to the 2013 International Consensus Meeting criteria. We evaluated the diagnostic performance of CRP, ESR, fibrinogen and NLR, both individually and in combinations, based on sensitivity, specificity, and area under the receiver operating characteristic curve. RESULTS: Of the 63 included patients, 32 were diagnosed with PJI. The area under the ROC curve was 0.821 for CRP, 0.794 for ESR, 0.885 for fibrinogen and 0.702 for NLR. CRP gave a sensitivity of 87.5% and specificity of 74.2% with an optimal predictive cut-off of 8.50 mg/mL. ESR gave a sensitivity of 81.3% and specificity of 71.0% with an optimal predictive cut-off of 33 mm/h. Plasma fibrinogen gave a comparatively higher sensitivity of 93.8% and specificity of 77.4% with an optimal predictive cut-off of 3.55 g/L, while NLR gave a moderate sensitivity of 84.4% but low specificity of 54.8% with an optimal predictive cut-off of 2.30. The combination of fibrinogen and CRP gave a high AUC of 0.897, an acceptable sensitivity of 75% and a high specificity 93.5%. CONCLUSIONS: Plasma fibrinogen is a cost-effective, convenient biomarker that can be used to rule out PJI in patients scheduled for re-revision arthroplasty. In combination with CRP, it may be effective in diagnosing PJI in such patients.

Poor performance of monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, and fibrinogen when screening for occult infection among patients with sequelae of suppurative hip arthritis before total hip arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) is considered the best treatment for sequelae of suppurative hip arthritis, but such patients are more likely to have occult infection and therefore to suffer post-operative periprosthetic joint infection. Our study examined (1) the occult infection rate among patients with sequelae of suppurative hip arthritis, and whether (2) neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), or fibrinogen levels can be used to screen such patients for occult infection before THA. METHODS: We retrospectively enrolled 428 patients who underwent primary THA at our hospital between 2010 and 2021, of whom 31 had occult infection and 397 did not. The maximum sensitivity and specificity were determined for the three indicators using receiver operating characteristic curves, and positive and negative predictive values were calculated. RESULTS: Patients with occult infection showed significantly higher erythrocyte sedimentation rate (ESR) and higher levels of C-reactive protein (CRP) and fibrinogen than those without occult infection. The various potential indicators gave the following areas under the receiver operating characteristic curves: ESR, 0.586; CRP, 0.599; interleukin-6, 0.651; NLR, 0.506; MLR, 0.600; and fibrinogen, 0.589. Sensitivity and specificity were as follows: ESR, 30.8% and 92.5%; CRP, 50.0% and 70.2%; interleukin-6, 57.7% and 67.5%; NLR, 46.7% and 62.9%; MLR, 60.0% and 61.7%; and fibrinogen, 43.3% and 81.7%. CONCLUSION: The rate of occult infection was 7.24% among our patients. ESR, NLR, MLR, and levels of CRP, interleukin-6, and fibrinogen may be unreliable for screening such patients for occult infection before THA according to sensitivity and specificity.

Evaluation of the rate of post-operative dislocation in patients with ipsilateral valgus knee deformity after primary total hip arthroplasty.

PURPOSE: There is scant literature on the evaluation of dislocation after total hip arthroplasty (THA) in patients with ipsilateral valgus knee deformity. This study aimed to investigate the post-operative dislocation rate in patients with valgus knee deformity who underwent ipsilateral THA and identify whether ipsilateral valgus knee deformity increases the dislocation rate after THA. METHODS: We retrospectively reviewed patients with valgus knee deformity who underwent ipsilateral THA in our institution from January 2016 to December 2018. Each hip with ipsilateral valgus knee deformity was matched with a hip without valgus knee deformity according to sex, affected side, and date of surgery. The primary outcome was the dislocation rate after THA. Univariate analyses were initially used to compare data between the dislocation group and the non-dislocation group. Independent risk factors for dislocation were determined using multivariate logistic regression. RESULTS: There were 257 THAs with ipsilateral valgus knee deformity (valgus knee group) and 257 THAs without valgus knee deformity (control group). The valgus knee group showed a significantly higher dislocation rate than the control group (9.7% versus 1.6%, p < 0.001). Older age (p = 0.020) and malposition of the acetabular cup (p = 0.048) were independent risk factors of post-operative dislocation. CONCLUSION: Patients with valgus knee deformity have a higher risk of dislocation after ipsilateral THA. If ipsilateral THA and total knee arthroplasty must be performed successively, total knee arthroplasty may have an earlier priority than THA.

Efficacy and safety of tranexamic acid in the treatment of adult melasma: An updated meta-analysis of randomized controlled trials.

WHAT IS KNOWN AND OBJECTIVE: Tranexamic acid (TXA) is a novel treatment option for melasma; however, no consensus exists on its use. This study evaluates the efficacy and safety of TXA for melasma. METHODS: A comprehensive literature review was conducted to search for randomized controlled trials comparing TXA alone, TXA as adjuvant to routine treatment and placebo. Changes in the Melasma Area Severity Index (MASI)/modified MASI (mMASI) between pre- and post-treatment and between a certain melasma treatment and TXA were the primary outcomes. Twenty-four trials comparing oral, topical or intradermal TXA with routine treatment were included in the meta-analysis. RESULTS AND DISCUSSION: The change in MASI/mMASI scores at 4 (MD, 3.58; 95% confidence interval (CI), 2.15-5.01), 8 (MD, 5.08; 95% CI, 3.34-6.81), 12 (MD, 4.89; 95% CI, 3.80-5.97) and 16 (MD, 6.55; 95% CI, 2.62-10.48) weeks after treatment was all less than the baseline scores, regardless of the delivery route. The reduction in the MASI/mMASI scores between TXA adjuvant and routine treatment at 4 (MD, -0.43; 95% CI, -0.79 to -0.08), 8 (MD, -0.81; 95% CI, -1.09 to -0.54), 12 (MD, -1.10; 95% CI, -1.78 to -0.43) and 16 (MD, -1.12; 95% CI, -1.51 to -0.74) weeks was significant. However, the superiority of TXA was not detected when the topical or intradermal route was adopted. No serious adverse events occurred with the use of TXA. WHAT IS NEW AND CONCLUSION: These results suggest that oral TXA is an available, effective and safe alternative treatment for melasma.

Is there a role of tranexamic acid in rheumatoid arthritis with total knee arthroplasty? Findings from a multicenter prospective cohort study in China.

BACKGROUND: Tranexamic acid (TXA) has proven to be effective in reducing the blood loss associated with total knee arthroplasty (TKA) in patients with osteoarthritis. However, there still exists a paucity of evidence regarding the effectiveness of intravenous TXA in patients with rheumatoid arthritis. The aim of this study was to explore the efficacy and safety of intravenous TXA on blood loss after TKA in Chinese patients with rheumatoid arthritis. MATERIALS AND METHODS: A total of 405 patients with rheumatoid arthritis who had undergone TKA were categorized into two groups based on the protocol of TXA use. TXA group (n = 248): patients received 15 mg/kg TXA prior to operation. Control group (n = 157): patients received no TXA. The outcome measurements such as, total blood loss (TBL), intraoperative blood loss (IBL), hidden blood loss (HBL), transfusion, drainage, the timing of first ambulation, the length of stay (LOS), total hospitalization costs, the results of 12-Item Short Form Survey (SF-12), the incidence of thromboembolic events and other complications were recorded and compared. RESULTS: The mean TBL, IBL, HBL, volume of transfusion and drainage were significantly lower in TXA group than in Control group. The rate of transfusion was significantly lower in TXA group than in Control group. There was a favorable effect in early ambulation for patients in TXA group, compared with patients in Control group. In addition, TXA group had shorter LOS, lower hospitalization costs and higher postoperative SF-12 score than Control group. The incidence of deep venous thrombosis and other complications did not differ between the two groups. CONCLUSION: TXA can effectively diminish blood loss, reduce transfusion, shorten LOS and decrease hospitalization costs after TKA in Chinese patients with rheumatoid arthritis, without increasing the risk of complications.

Oral mosapride can provide additional anti-emetic efficacy following total joint arthroplasty under general anesthesia: a randomized, double-blinded clinical trial.

BACKGROUND: We sought to determine (1) whether the addition of prophylactic oral mosapride to a protocol including dexamethasone and ondansetron further reduces postoperative nausea and vomiting (PONV) compared with ondansetron alone or the combination of both; (2) whether preemptive application of oral mosapride provides additional clinical benefits for bowel function and appetite, thus improving functional recovery. METHODS: We randomized 240 patients undergoing total hip and knee arthroplasty to receive placebo (Control, n = 80), dexamethasone (10 mg) before anesthesia induction (Dexa, n = 82), or dexamethasone (10 mg) before anesthesia induction as well as oral mosapride (5 mg) before and after surgery (Mosa+Dexa, n = 78). Patients were assessed at 0-6, 6-12, 12-24, and 24-48 h postoperatively. Primary outcomes were incidence and severity of PONV as well as complete response. Secondary outcomes were appetite, time until first defecation and ambulation, patient satisfaction score, and length of hospital stay. RESULTS: Mosa+Dexa patients showed significantly lower incidence of nausea at 6-12 h (3.8%) and over the entire evaluation period (6.4%), as well as a higher rate of complete response (89.7%) than other patients. Mosa+Dexa patients required less time to achieve first defecation and ambulation, they were hospitalized for shorter time, and they were more satisfied with clinical care. CONCLUSION: Addition of oral mosapride further reduced incidence of PONV, especially postoperative nausea, during 6-12 h postoperatively. Moreover, preemptive application of oral mosapride can further improve appetite, bowel function, ambulation and length of hospital stay. TRIAL REGISTRATION: The study protocol was registered at the Chinese Clinical Trial Registry ( ChiCTR1800015896 ), prospectively registered on 27/04/2018.

Tourniquet use in routine primary total knee arthroplasty is associated with a higher transfusion rate and longer postoperative length of stay: a real-world study.

BACKGROUND: In an enhanced recovery after surgery program, a growing number of orthopedists are reconsidering the necessity of tourniquet use in total knee arthroplasty (TKA). However, the impact of tourniquet use on transfusion rate and postoperative length of stay (PLOS) in TKA remains controversial. Therefore, we carried out a study to investigate the effect of tourniquet application in routine primary TKA on transfusion rate and PLOS. METHODS: We analyzed data from 6325 patients who underwent primary unilateral TKA and divided them into two groups according to whether a tourniquet was applied during the procedure, and a tourniquet was used in 4902 and not used in 1423. The information for transfusion and PLOS was extracted from patients' electronic health records, and the data were analyzed with logistic and linear regression analyses. RESULTS: Following TKA, the transfusion rate and PLOS were 14.52% and 7.72 ± 3.54 days, respectively, in the tourniquet group, and 6.47% and 6.44 ± 3.48 days, respectively, in the no-tourniquet group. After adjusting for the different related variables, tourniquet use was significantly correlated with a higher transfusion rate (risk ratio = 1.888, 95% confidence interval (CI) 1.449-2.461, P < 0.001) and a longer PLOS (partial regression coefficient (B) = 0.923, 95%CI 0.690-1.156, P < 0.001). CONCLUSIONS: Our findings suggested that tourniquet use in routine primary TKA was related to a higher transfusion rate and a longer PLOS. The impact of tourniquet use on transfusion rate and PLOS should be taken into account in clinical practice.

Plasma Fibrinogen and Platelet Count Are Referable Tools for Diagnosing Periprosthetic Joint Infection: A Single-Center Retrospective Cohort Study.

BACKGROUND: Although the MusculoSkeletal Infection Society has suggested a series of markers to diagnose periprosthetic joint infection (PJI), no single marker can accurately identify infection before revision hip or knee arthroplasty, and exploring promising markers to easily and reliably diagnose PJI is ongoing. The aim of this study was to evaluate the diagnostic value of plasma fibrinogen and platelet count for diagnosing PJI. METHODS: We retrospectively included 439 patients who underwent revision arthroplasty from January 2008 to December 2018; 79 patients with coagulation-related comorbidities were evaluated separately. The remaining 360 patients constituted 153 PJI and 207 non-PJI patients. Receiver operating characteristic curves were used to evaluate the maximum sensitivity and specificity of the tested markers. RESULTS: The receiver operating characteristic curves showed that the areas under the curve for plasma fibrinogen, platelet count, and serum C-reactive protein and erythrocyte sedimentation rate were 0.834, 0.746, 0.887, and 0.842, respectively. Based on Youden's index, the optimal predictive cutoffs for fibrinogen and platelet count were 3.57 g/L and 221 × 109/L, respectively. The sensitivity and specificity, respectively, were 68.6% and 86.0% (fibrinogen) and 57.5% and 83.1% (platelet count) for diagnosing PJI. The sensitivity and specificity, respectively, were 76.7% and 72.2% (fibrinogen) and 48.8% and 63.9% (platelet count) for diagnosing PJI in patients with coagulation-related comorbidities. CONCLUSION: Plasma fibrinogen performed well for diagnosing PJI before revision arthroplasty, and its value neared that of traditional inflammatory markers. Although the diagnostic value of the platelet count was inferior to traditional markers, its diagnostic value was fair for diagnosing PJI. Fibrinogen also may be useful for diagnosing PJI in patients with coagulation-related comorbidities.

The antifibrinolytic and anti-inflammatory effects of a high initial-dose tranexamic acid in total knee arthroplasty: a randomized controlled trial.

PURPOSE: The aim of this study was to evaluate the effects of a high initial-dose (60 mg/kg) intravenous tranexamic acid (IV-TXA) on fibrinolysis and inflammation after total knee arthroplasty (TKA). METHODS: A total of 132 patients were categorized into two groups based on different TXA regimens: 20 mg/kg before incision (A) or 60 mg/kg before incision (B). All patients received five doses of 1 g TXA at three, six, 12, 18, and 24 hours after the first dose. The primary outcomes were peri-operative blood loss and transfusion rate. Other outcome measurements such as, haemoglobin level, fibrinolysis parameters [fibrin(-ogen) degradation products (FDP), D-dimer], inflammatory factors [C-reactive protein (CRP), interleukin-6 (IL-6)], visual analog scale (VAS) score, consumption of analgesic rescue, coagulation parameters [activated partial thromboplastin time (APTT), prothrombin time (PT), platelet count, thrombelastography (TEG), and anti-factor Xa activity (AFXa)] and complications, were also compared. RESULTS: There was a favourable effect in reducing peri-operative blood loss and transfusion rate for patients in Group B, compared with patients in Group A. In addition, the levels of FDP, D-dimer, CRP, IL-6, and dynamic pain in Group B were significantly lower than those in Group A on post-operative days one, two and three. There were no statistically significant differences in postoperative coagulation parameters and complications between the two groups. CONCLUSION: A high initial-dose (60 mg/kg) IV-TXA before surgery followed by five doses can further reduce blood loss, provide additional fibrinolysis and inflammation control, and ameliorate post-operative pain following TKA, without increasing the risk of treatment-related complications.

Tranexamic acid attenuates inflammatory effect and modulates immune response in primary total knee arthroplasty: a randomized, placebo-controlled, pilot trial.

AIMS: To explore the effect of intravenous tranexamic acid (IV-TXA) on inflammation and immune response following primary total knee arthroplasty (TKA). METHODS: Primary TKA patients (n = 125) were randomized into the following four groups: group A to receive placebo; group B to receive a single dose of 20 mg kg-1 IV-TXA and 20 mg of intravenous dexamethasone (IV-DXM); group C to receive six doses of IV-TXA (total dosage > 6 g); and group D to receive six doses of IV-TXA combined with three doses of IV-DXM (total dosage = 40 mg). The primary outcomes were C-reactive protein (CRP) and interleukin (IL)-6 levels and the secondary outcomes were complement C3 and C4 and T-cell subset levels, which were measured preoperatively and at 24 h, 48 h, 72 h, and 2 weeks postoperatively. RESULTS: The postoperative peak CRP and IL-6 levels in group C (93.7 ± 22.2 mg L-1, 108.8 ± 41.7 pg mL-1) were lower compared with those in group A (134.7 ± 28.8 mg L-1, P < 0.01; 161.6 ± 64.4 pg mL-1, P < 0.01). Groups B and D exhibited significantly lower CRP and IL-6 levels compared with groups A and C at 24 h, 48 h, and 72 h postoperatively (P < 0.05 for all). In group C, complement C3 and C4 levels were higher compared with those in group A at 48 h (0.967 ± 0.127 g L-1 vs. 0.792 ± 0.100 g L-1, P < 0.01; 0.221 ± 0.046 g L-1 vs. 0.167 ± 0.028 g L-1, P < 0.01) and 72 h (1.050 ± 0.181 g L-1 vs. 0.860 ± 0.126 g L-1, P = 0.01; 0.240 ± 0.052 g L-1 vs. 0.182 ± 0.036 g L-1, P < 0.01) postoperatively and CD3 and CD4 subset levels were higher compared with those in group B at 24 h postoperatively (66.78 ± 9.29% vs. 56.10 ± 12.47%, P < 0.05; 36.69 ± 5.78% vs. 28.39 ± 8.89%, P < 0.05). CONCLUSION: Six doses of IV-TXA could attenuate the inflammatory effect, modulate the immune response, and reduce immunosuppression caused by DXM in patients after TKA.

Additional benefits of multiple-dose tranexamic acid to anti-fibrinolysis and anti-inflammation in total knee arthroplasty: a randomized controlled trial.

BACKGROUND: Consensus is lacking regarding the dose and timing of tranexamic acid (TXA). The aim of this study was to determine whether multiple-dose intravenous TXA further reduced blood loss and attenuated inflammation after total knee arthroplasty (TKA). MATERIALS AND METHODS: We prospectively studied four regimens on TXA: no TXA (A), before incision, 3, 6, and 12 h later (B), before incision, 3, 6, 12, and 18 h later (C) and before incision, 3, 6, 12, 18, and 24 h later (D). The primary outcome was hidden blood loss (HBL). Other outcome measurements such as total blood loss (TBL), intraoperative blood loss (IBL), fibrinolysis parameters [fibrin(-ogen) degradation products, D-dimer], inflammatory factors (C-reactive protein, interleukin-6), visual analog scale (VAS) score, transfusion rate, length of stay (LOS) and complications were also compared. RESULTS: The mean HBL and TBL were significantly lower in Group D than in Groups C, B and A. The level of inflammatory factors and fibrinolysis parameters were significantly lower in Group D than in Groups C, B and A at 24 and 72 h postoperatively. The VAS score on postoperative days 1 and 3 (POD1 and POD3) was significantly lower in Group D than in Groups C, B and A. There was no significant difference in LOS among groups. No patient underwent blood transfusion. No episodes of deep venous thrombosis or pulmonary embolism occurred in all the groups. CONCLUSION: The repeated doses of TXA up to 24 h can further diminish HBL, provide additional fibrinolysis and inflammation control and ameliorate postoperative pain following TKA. LEVEL OF EVIDENCE: I.

Optimal route for administering tranexamic acid in primary unilateral total hip arthroplasty: Results from a multicenter cohort study.

AIM: This study aimed to compare the efficacy and safety of different tranexamic acid (TXA) routes following primary total hip arthroplasty (THA). METHODS: We collected data from the National Health Database on patients registered from January 2013 to September 2017. The patients were divided based on TXA administration route into a control group (without TXA), intravenous group, topical group and combined group. The primary outcome was transfusion; secondary outcomes were total blood loss, haemoglobin level, decrease in haemoglobin on postoperative day 3, and incidence of complications. RESULTS: Data were collected on 7667 primary THA, 4662 with TXA and 3005 without TXA. The transfusion rate was 28.7% in the control group, 12.7% in the topical group, 8.9% in the intravenous group, and 6.1% in the combined group, and the inter-group differences were significant (P < .01). The combined group showed significantly smaller total blood loss (1.23 ± 0.52 L), smaller reduction in haemoglobin level (26.5 ± 11.1 g/L) and higher haemoglobin level on postoperative day 3 (107.0 ± 15.5 g/L) than the other three groups (P < .05). The three TXA groups showed significantly lower incidence of deep vein thrombosis than the control group (0.08% vs 0.47%, P = .001) as well as a lower rate of other complications (0.34% vs 0.67%, P = .044). CONCLUSION: TXA is effective and safe to decrease blood loss and transfusion following primary THA, regardless of whether it is administered intravenously, topically or both. Intravenous or combined routes may produce better haemostatic effects, so they may be suggested in the absence of contraindications.

Efficacy and safety of tranexamic acid in geriatric hip fracture with hemiarthroplasty: a retrospective cohort study.

BACKGROUND: Geriatric hip fracture patients are particularly susceptible to blood loss and venous thromboembolism (VTE) during hemiarthroplasty, yet relatively few studies have examined the safety and efficacy of tranexamic acid (TXA) in these patients. METHODS: This cohort study of hip fracture patients (≥65 years) undergoing hemiarthroplasty between January 2013 and September 2016 involved 289 patients who received 15 mg/kg TXA prior to surgery and 320 who received no TXA. All patients underwent a fast-track program including nutrition, blood, and pain management; VTE prophylaxis; early mobilization; and early intake. The primary outcome was red cell transfusion requirement. Secondary outcomes included blood loss, hemoglobin (Hb) level, VTE, adverse events and length of hospital stay. Multivariate logistic regression and meta-analysis of the literature were also performed to control for confounding factors and identify risk factors of red cell transfusion. RESULTS: The proportion of patients receiving at least 1 U of erythrocytes was significantly lower in the TXA group (8.65%) than in the control group (24.06%, OR 0.299, p < 0.001). Mean Hb level was significantly higher in the TXA group on postoperative day 1 (111.70 ± 18.40 vs 107.29 ± 18.70 g/L, p = 0.008) and postoperative day 3 (108.16 ± 17.25 vs 104.22 ± 15.16 g/L, p = 0.005). A significantly higher proportion of TXA patients began to ambulate within 24 h after surgery (37.02% vs 26.25%, p = 0.004), and their length of hospitalization was significantly shorter (11.82 ± 4.39 vs 15.96 ± 7.30 days, p = 0.003). TXA did not increase risk of DVT (OR 0.70, 95%CI 0.25 to 1.97). Logistic regression showed that, after adjusting for covariates, TXA was associated with 62% lower risk of red blood cell transfusion (0.327, 95%CI 0.214 to 0.696), and a similar result was obtained in meta-analysis of unadjusted data from the present study and the literature (OR 0.33, 95%CI 0.25 to 0.43). CONCLUSION: TXA appears to be safe and effective for reducing blood loss and red blood cell transfusion in geriatric hip fracture patients undergoing fast-track hemiarthroplasty.

Plasma Fibrin Degradation Product and D-Dimer Are of Limited Value for Diagnosing Periprosthetic Joint Infection.

BACKGROUND: Although the Musculoskeletal Infection Society introduced the use of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as inflammatory markers for diagnosing periprosthetic joint infection (PJI), no single blood marker reliably detects infection before revision arthroplasty. We therefore posed 2 questions: (1) Are fibrin degradation product (FDP) and D-dimer of value for diagnosing PJI before revision arthroplasty? (2) What are their sensitivity and specificity for that purpose? METHODS: To answer these questions, we retrospectively enrolled 318 patients (129 with PJI [group A], 189 with aseptic mechanical failure [group B]) who underwent revision arthroplasty during 2013-2018. Receiver operating characteristic curves were used to determine maximum sensitivity and specificity of the 2 markers. Inflammatory and fibrinolytic markers were evaluated based on (1) the Tsukayama-type infection present and (2) the 3 most common PJI-related pathogens. RESULTS: FDP and D-dimer levels were higher in group A than in group B: 4.97 ± 2.83 vs 4.14 ± 2.67 mg/L and 2.14 ± 2.01 vs 1.51 ± 1.37 mg/L fibrinogen equivalent units (FEU), respectively (both P < .05). Based on the Youden index, 2.95 mg/L and 1.02 mg/L FEU are the optimal FDP and D-dimer predictive cutoffs, respectively, for diagnosing PJI. Sensitivity and specificity, respectively, were 65.12% and 60.33% (FDP) and 68.29% and 50.70% (D-dimer). ESR, CRP, and interleukin-6 values were diagnostically superior to those of FDP and D-dimer. CONCLUSION: The value of plasma FDP and D-dimer for diagnosing PJI is limited compared with traditional inflammatory markers (ESR, CRP, interleukin-6) before revision arthroplasty.

Analysis of a large data set to identify predictors of blood transfusion in primary total hip and knee arthroplasty.

BACKGROUND: The aim of this study was to identify the predictors of need for allogenic blood transfusion (ALBT) in primary lower limb total joint arthroplasty (TJA). STUDY DESIGN AND METHODS: This study utilized a large dataset of 15,187 patients undergoing primary unilateral TJA. Risk factors and demographic information were extracted from the electronic health record. A predictive model was developed by both a random forest (RF) algorithm and logistic regression (LR). The area under the receiver operating characteristic curve (AUC-ROC) was used to compare the accuracy of the two methods. RESULTS: The rate of ALBT was 18.9% in total. Patient-related factors associated with higher risk of an ALBT included female sex, American Society of Anesthesiologists (ASA) II, ASA III, and ASA IV. Surgery-related risk factors for ALBT were operative time, drain use, and amount of intraoperative blood loss. Higher preoperative hemoglobin and tranexamic acid use were associated with decreased risk for ALBT. The RF model had a better predictive accuracy (area under the curve [AUC] 0.84) than the LR model (AUC, 0.77; p < 0.001). CONCLUSION: The risk factors identified in the current study can provide specific, personalized perioperative ALBT risk assessment for a patient considering lower limb TJA. Furthermore, the predictive accuracy of the RF algorithm was significantly higher than that of LR, making it a potential tool for future personalized preoperative prediction of risk for perioperative ALBT.

Multiple Doses of Perioperative Dexamethasone Further Improve Clinical Outcomes After Total Knee Arthroplasty: A Prospective, Randomized, Controlled Study.

BACKGROUND: This study aimed to evaluate the effect and safety of multiple doses of preoperative dexamethasone on pain and recovery after total knee arthroplasty (TKA). METHODS: Altogether, 182 patients undergoing TKA received 3 intravenous injections of normal saline (group A), 1 injection of high-dose dexamethasone (20 mg) and 2 injections of normal saline (group B), or 1 injection of high-dose dexamethasone and 2 injections of low-dose (10 mg) dexamethasone (group C). RESULTS: Visual analog scale was lower in group C than in group A or B and was different between groups A and B on postoperative days 1, 2, and 3 (all P < .05). Fewer group C patients required analgesic rescue and had lower total analgesic than those in group A or B, with the same difference between groups A and B (all P < .05). C-reactive protein and interleukin-6 levels were lower in groups B and C than in group A at 24, 48, and 72 hours postoperatively. C-reactive protein at 72 hours and interleukin-6 at 48 and 72 hours were lower in group C than in group B (all P < .05). Incidences of postoperative nausea and vomiting, number of patients requiring antiemetic rescue, and overall consumption of metoclopramide were lower in groups B and C than in group A (all P < .05). No surgical-site infections or gastrointestinal hemorrhages were detected in any group. CONCLUSION: Multiple dexamethasone doses further reduced postoperative pain, decreased consumption of analgesic drugs, and provided more powered inflammation control. These findings call for further studies to further evaluate its safety.