Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study.

BACKGROUND: We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA). METHODS: For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay. RESULTS: The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P <  0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05). CONCLUSION: In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).

Effect of Multiple Doses of Intravenous Tranexamic Acid on Perioperative Blood Loss in Total Knee Arthroplasty: A Randomized Controlled Study.

OBJECTIVE: To identify the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) following primary total knee arthroplasty (TKA) with a tourniquet. METHODS: This is a single-blind randomized controlled study that recruited osteoarthritis patients who had undergone primary unilateral TKA from May 2019 to May 2020 at our medical center. A total of 300 patients were randomly divided into three groups to receive: one dose (1 g) of IV-TXA before skin incision combined with one dose (1.5 g) of intra-articular tranexamic acid（IA-TXA) followed by a single dose of IV-TXA (1 g) for 3 h (group A); two doses of IV-TXA (1 g) for 3 and 6 h (group B); or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group C) postoperatively. TKA with a tourniquet was performed by the same surgical team. The primary outcomes were total blood cell loss (TBL), hidden blood loss (HBL), maximum hemoglobin (Hb) drop, and transfusion rate. Secondary outcomes were levels of C-reactive protein (CRP) and D-dimer, and the incidence of postoperative complications. One-way analysis of variance, subgroup analysis, and multivariate correlation analysis were used to calculate the differences among the three groups. RESULTS: The study included 56 male and 244 female patients aged 60-80 years. The mean TBL, the mean HBL, and the maximum Hb drop in group C (471.2 ± 190.6 mL, 428.4 ± 190.3 mL, and 21.2 ± 3.8 g/L, respectively) were significantly lower than those in groups B (563.4 ± 224.6 mL, P = 0.030; 519.9 ± 226.4 mL, P = 0.033; and 23.2 ± 4.1 g/L, P = 0.001, respectively), and A (651.6 ± 254.1 mL, P < 0.001; 607.1 ± 254.3 mL, P < 0.001; and 25.1 ± 4.3 g/L, P < 0.001, respectively). No transfusions were required. The postoperative acute inflammatory reaction was less problematic for patients in Group C, and the incidence of thromboembolic events was similar among the groups (P > 0.05). In addition, there were positive correlations between the HBL and the tourniquet inflation time (r = 0.844, P < 0.001). Similarly, the level of CRP on POD1 (r = 0.393, P < 0.001) and POD3 (r = 0.149, P = 0.010), and the level of D-dimer on POD1 (r = 0.382, P < 0.001) were positively correlated with the HBL. CONCLUSION: Three doses of postoperative IV-TXA decreased blood loss and diminished the postoperative inflammatory and fibrinolytic response more than a single dose or two doses in elderly patients following TKA without increasing the incidence of adverse events.

Multiple-dose tranexamic acid for perioperative blood loss in total knee arthroplasty in patients with rheumatoid arthritis：a single-blinded, randomised, parallel-controlled study protocol in China.

INTRODUCTION: This clinical trial is designed to evaluate the effect of multiple-dose tranexamic acid (TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA). METHODS AND ANALYSIS: A randomised, single-blinded, parallel-controlled study will be designed. Patients with RA (age 50-75 years) undergoing unilateral primary end-stage total knee arthroplasty will be randomly divided into group A or group B. Group A will be treated with one dose of TXA (1 g; intravenous injection 3 hours postsurgery) and group B with three doses (1 g; intravenous injection at 3, 6 and 12 hours postsurgery) after surgery. The primary outcomes will be evaluated with blood loss, maximum haemoglobin drop and transfusion rate. The secondary outcomes will be evaluated with knee function and complications. ETHICS AND DISSEMINATION: The Shanghai Guanghua Hospital of Integrated Traditional Chinese Medicine and Western Medicine Ethics Committee approved in this study in July 2019. Informed consent will be obtained from all participants. Results of the trial will be published in the Dryad and repository in a peer-reviewed journal. Additionally, deidentified data collected and analysed for this study will be available for review from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: ChiCTR1900025013.

Reverse Shoulder Arthroplasty in Patients with Rheumatoid Arthritis: Early Outcomes, Pitfalls, and Challenges.

OBJECTIVE: To evaluate the early outcomes and risk factors of reverse shoulder arthroplasty (RSA) in patients with rheumatoid arthritis (RA). METHODS: A retrospective study was performed on RA patients who had undergone RSA between January 2016 and January 2018. Preoperative glenohumeral joint damage was evaluated according to two radiographic classification systems. The severity of joint damage was estimated using Larsen's method, while the Levigne-Franceschi method was used to assess the type of destruction. Further, we recorded intra- and postoperative complications. Visual Analogue Scale (VAS) was used to assess the degree of shoulder pain while shoulder function was evaluated with the American Shoulder and Elbow Surgeons (ASES) Shoulder Score. In addition, patients' subjective outcome and range of shoulder motion were recorded. Radiographs were taken and examined during the follow-up period. Paired t-test was used to determine the difference in measurement data between preoperative and the last follow-up. VAS was analyzed using the Wilcoxon matched-pairs signed-rank test. RESULTS: A total of 14 patients with 14 shoulders were included. All the patients were female with an average age of 60.29 years (range, 49-71 years) at the time of surgery and an average RA disease duration of 24.57 years (range, 5-40 years). Seven of the 14 patients had a history of joint surgery related to RA. Meanwhile, 11 of the 14 shoulders showed glenoid bone defect, and eccentric reaming was performed intraoperatively to avoid base plate malposition. The mean follow-up period for the 14 patients was 2.76 years (range, 2-4 years). The mean VAS decreased from a value of 5.71 ± 1.10 preoperatively to 1.36 ± 0.61 postoperatively (P < 0.001). On the contrary, the ASES score showed an increase from 33.93 ± 6.89 to 76.67 ± 5.23 (P < 0.001). An increase in active forward elevation, abduction, and external rotation with the arm in 90° of abduction from 85.71° ± 17.61°, 77.14° ± 19.43°, and 17.14° ± 10.97° to 126.43° ± 5.23°, 106.42° ± 11.72°, and 38.57° ± 14.57°, respectively, was observed (P < 0.001). Subjective outcome assessment showed that 13 of the 14 patients were very satisfied or satisfied with the operation, while one patient was uncertain due to co-existing ipsilateral elbow lesion. Notably, one patient acquired a humeral periprosthetic fracture during the operation. In this study, no major complications such as periprosthetic joint infection and dislocation or implant loosening were observed. Further, no patients underwent revision for any reason at the end of the follow-up. CONCLUSIONS: RSA could achieve good early outcomes without high complication rates in patients with RA. Glenoid bone defects and adjacent joints involvement were common in this patient group, which might increase the risk of surgery and affect postoperative satisfaction.

[Clinical study on the control of intra-articular hemorrhage by tranexamic acid after shoulder arthroscopy].

OBJECTIVE: To explore clinical effects of tranexamic acid on postoperative intra-articular hemorrhage after shoulder arthroscopy. METHODS: From February to July 2018, 60 patients with rotator cuff tears treated by shoulder arthroscopy were randomly divided into observation group and control group, 30 cases in each group. In observation group, there were 6 males and 24 females; aged from 55 to 70 years old with an average age of (62.3±5.5) years; the courses of disease ranged from 2 to 36 months with an average of (11.7±1.7) months; received 0.5 g tranexamic acid (1 g of tranexamic acid was diluted with normal saline to 20 ml) in each articular cavity and subacromial space after operation. In control group, there were 5 males and 25 females; aged from 56 to 72 years old with an average of (63.4±5.8) years old; the courses of disease ranged from 4 to 36 months with an average of (10.8±1.4) months; 10 ml of normal saline was injected into joint cavity and subacromial space. Hemoglobin values between two groups before and after operation at 1 day were recorded, circumference of shoulder joint was measured preoperatively and the 1st and 7th days after operation, and circumference difference of shoulder joint was recorded. Complications such as subcutaneous blood stasis and DVT were recorded. RESULTS: There was no significant difference in hemoglobin values between two groups before and after operation at 1 day (P>0.05) . On the first day after surgery, peripheral diameter of shoulder joint in observation group [(32.9±0.3) cm ] was significantly lower than that in control group [(35.1±0.5) cm ], and the circumference difference of shoulder joint in observation group [(8.7±0.4) mm ] was also significantly lower than that in control group [(12.3±0.5) mm ], the difference was statistically significant (P<0.05) . However, there was no significant difference in circumference of shoulder joint and the difference in circumference of shoulder joint between two groups on the 7th day after operation (P>0.05) . Two patients in observation group occurred subcutaneous ecchymosis, while 6 patients occurred in control group, but without statistical difference between two groups (P>0.05) . CONCLUSION: Subacromial and articular injection of tranexamic acid could significantly reduce early swelling of soft tissue after arthroscopic shoulder surgery, and it has better safety.

[Patellofemoral arthroplasty for the treatment of patellofemoral arthritis].

OBJECTIVE: To explore the clinical effect of patellofemoral joint replacement in the treatment of patellofemoral arthritis. METHODS: From July 2013 to June 2017, 35 patients with 42 knees underwent patellofemoral arthroplasty, including 34 females and 1 male, aged 45 to 70 (55.0±8.2) years old, with a course of 6 to 36 (13.7±2.5) months. Before and at the end of the follow-up, the patients were assessed with Oxford knee score, satisfaction with the operation was assessed at the end of the follow-up. In addition, X-ray films of the front and side of the knee joint and axial films of the patella were taken to assess whether the prosthesis was loose, and complications such as hematoma and joint infection were recorded. RESULTS: Forty-two knees of 35 patients were followed up for 18 to 65 (35.0±7.2) months, and the operation time was (56.2±8.7) min. Oxford knee joint score increased from preoperative 28.14±0.36 to 37.19±0.47 at the end of the follow-up (P<0.05) . The score of pain items increased from preoperative 10.12±0.26 to 15.83±0.30 at the end of the follow-up, and the score of functional items increased from preoperative 18.02±0.13 to 21.36±0.23 at the end of the follow-up (P<0.05) , there was statistical significance (P <0.05) . In one case, there was wound suture reaction in the early postoperative period, which was improved after debridement; in the other case, there was swelling around the wound 5 weeks after operation, which was improved after antibiotic treatment; in one case, there was tear at the suture of quadriceps femoris muscle at 1 month after operation, which was improved after re suture; no loosening of prosthesis was found. CONCLUSION: The second generation of patellofemoral arthroplasty for the treatment of simple severe patellofemoral arthritis has satisfactory early clinical effect and few complications, but the indication of operation should be strictly grasped. For severe cases, CT scan of knee joint can be used to customize the patellofemoral prosthesis, so as to reduce postoperative complications and improve the clinical effect.

[Comparison of analgesic effects between multimodal and patient-controlled intravenous analgesia in patients with rheumatoid arthritis in the perioperative period of total knee arthroplasty].

OBJECTIVE: To compare the analgesic effect between multimodal and patient-controlled intravenous analgesia(PCIA) in patients with rheumatoid arthritis(RA) in the perioperative period of knee joint replacement. METHODS: From June 2015 to June 2016, 40 RA patients undergoing total knee arthroplasty were randomly divided into two groups. There were 20 patients in PCIA group, including 3 males and 17 females, with an average age of(59.6±2.3) years old, who received controlled instillation of sufentanil analgesia controlled by an intravenous analgesia pump. There were 20 patients in multiple model analgesia group, including 2 males and 18 females, with an average age of(56.3±1.3) years old, who were treated with continuous femoral nerve block, local injection of knee joint and combined buprenorphine patches. The VAS score and the incidence of adverse reactions and HSS score were compared between the two groups after operation. The advantages and disadvantages of the two modes of analgesia were evaluated. RESULTS: On the 6 th and 24 th hours after surgery, the VAS scores of the multimodal analgesia group were significantly lower than those of the PCIA group(P<0.01). On the 48 th hour after surgery, the VAS scores was significantly lower in the multimodal analgesia group than those in PCIA group(P<0.000 1), both in the state of motion and at rest. On the 1 st week after surgery, the HSS score of the multimodal analgesia group was significantly higher than that in the PCIA group(P<0.000 1). The pain score and the degree of activity in HSS score of the multimodal analgesia group were better than those in PCIA group (P<0.05). The functional score of multimodal analgesia group was significantly better than that of PCIA group(P<0.01). But there was no significant difference in muscle strength scores between two groups. CONCLUSIONS: Multimodal analgesia is an ideal analgesic plan for total knee arthroplasty TKA patients with RA in perioperative period, which has good effects and little adverse reaction.

Disorders in angiogenesis and redox pathways are main factors contributing to the progression of rheumatoid arthritis: a comparative proteomics study.

OBJECTIVE: To clarify the pathogenesis of rheumatoid arthritis (RA) by comparing protein expression in fibroblast-like synoviocytes (FLS) from patients with RA with that in FLS from normal subjects, using proteomics analysis. METHODS: Proteins extracted from primary cultures of FLS obtained from 50 patients with RA and 10 normal subjects were analyzed by automated 2-dimensional nano-electrospray ionization liquid chromatography tandem mass spectometry. Differentially expressed proteins were screened by 2-sample t-test (P < 0.05) and fold change (>1.5), based on the bioinformatics analysis. The expression of vasculature development-related proteins (Thy-1, connective tissue growth factor [CTGF], and thrombospondin 1 [TSP-1]) and redox-related proteins (superoxide dismutase 2 [SOD2]) in synovial tissue was confirmed by real-time polymerase chain reaction and Western blotting. The effect of Thy-1 and CTGF knockdown on Thy-1, CTGF, TSP-1, and vascular endothelial growth factor (VEGF) was analyzed by RNA interference experiments. RESULTS: According to the criteria of having >1 unique peptide per protein present and a false discovery rate of ≤5%, 1,060 proteins were identified from patients with RA, and 1,292 proteins were identified from normal subjects, from which 100 differentially expressed proteins were screened out from the RA proteins. Of these, 46 proteins were up-regulated, and the remaining 54 proteins were down-regulated. Gene ontology and pathway analyses showed that 6 vasculature development-related proteins were up-regulated, including Thy-1, CTGF, and TSP-1, while 11 redox-related proteins were down-regulated, including SOD2. The results were consistent with those obtained using mass spectrometry. Thy-1, VEGF, CTGF, and TSP-1 were down-regulated after Thy-1 knockdown, and VEGF and CTGF were down-regulated after CTGF knockdown. Recombinant human CTGF could enhance proliferation and Transwell migration of human umbilical vein endothelial cells. CONCLUSION: Up-regulation of vasculature development-related proteins and down-regulation of redox-related proteins in FLS are predominant factors that may contribute to the pathogenesis of RA.

[Clinical result of forefoot correction by the first ray stabilization combined with resection of the lesser metatarsal head procedure for patient with rheumatoid arthritis].

OBJECTIVE: To introduce the procedure of the 1st ray stabilization combined with resection of the lesser metatarsal heads for patient with severe forefoot deformity caused by rheumatoid arthritis (RA) and evaluate the short to mid-term clinical results. METHODS: From Oct. 2006 to Aug. 2010,97 patients (129 feet) aged from 36 to 67 years (average 54), with forefoot deformity caused by rheumatoid arthritis were reviwed. There were 88 males and 9 females,65 single lateral involved and 32 bilateral involved, the average duration of disease was 17 years (6 to 32 years). The 1st ray instability and lesser metatarsophalangeal (MTP) joint stiff dislocation were found in all cases. The first ray stabilization combined with resection of the lesser metatarsal head procedure were performed for all cases. The radiographic Hallux valgus angle (HVA) and intermetatarsal angle (IMA) were measurde and the JSSF (Japanese Society for Surgery of the Foot) score were evaluated before operation and every follow up. RESULTS: The average followed-up was 37 months (6 to 52 months) for all patients except 5 (7 feet) and 1 died for acute cardiac infarction 1 year after operation. The average JSSF score improved from (33.2 +/- 8.2) points preoperative to (67.3 +/- 3.1) points at final followed-up (P < 0.01); the average HVA was corrected from (50.0 +/- 11.8) degrees preoperative to (21.2 +/- 3.2) degrees at final follow up (P < 0.01); the average IMA was corrected from (15.5 +/- 3.6) degrees preoperative to (9.7 +/- 6.6) degrees at final follow up (P < 0.01). MTP joint nonunion was found in 4 feet. A radiographic high density mass was found in the 1st cuneiform bone during 8 to 11 months followed-up in 3 feet; delayed wound healing was happened in 9 feet; MTP joint infection was happened in 2 feet; tarsometatarsal joint infection was happened in 1 foot; lesser MTP joints deformity recurrence were found in 16 feet. CONCLUSION: The characters of forefoot with RA in later stage are the 1st ray deformity and instability compound with the lesser toes deformity. The 1st ray stability procedure which include the 1st MTP arthrodesis and the Lapidus procedure can correct the 1st ray deformities and rebuilt its stability. The lesser toes metatarsal head resection is effective in correct their deformity. This combined procedure is reliable. It is suitable for patients with severe Hallux valgus, increased IMA, tarsometatarsal joint instability and the lesser MTP joint stiff dislocation.

Connective tissue growth factor, a regulator related with 10-hydroxy-2-decenoic acid down-regulate MMPs in rheumatoid arthritis.

10-hydroxy-2-decenoic acid (10H2DA) is suggested to be a potential medication for rheumatoid arthritis (RA) by activation of matrix metalloproteinases (MMPs) via mitogen-activated protein kinase signaling pathways. The aim of the present work was to seek differentially expressed proteins in rheumatoid arthritis synovial fibroblasts (RASFs) treated with 10H2DA by comparative proteomics analysis. Two-dimensional electrophoresis (2-DE) and LC-MS/MS were performed to identify changes in protein expression after 24-h 10H2DA treatment. Differentially expressed proteins were identified by real-time PCR and Western blot analysis. Influence of down-regulation of connective tissue growth factor (CTGF) expression on MMPs was studied by RNAi. Ten proteins were up-regulated and 9 proteins were down-regulated after 24-h 10H2DA treatment. A total of 19 differentially expressed proteins were identified and found to be associated with glycolysis, lipid metabolism, cell adhesion, ATP synthesis, oxidation reduction, and anti-apoptosis. CTGF, a member of the C-terminal cystein-rich proteins (CCN) family, was down-regulated after 24-h 10H2DA treatment. MMPs were down-regulated after RNAi (CTGFi). These results suggest that CTGF is a regulator factor in the expression of MMPs, and 10H2DA down-regulate the concentration of MMPs probably by down-regulating the expression of CTGF.