Reconstruction of the medial patellofemoral ligament through a double bundle of a single patellar tract and quadriceps tendons combined with medial displacement of lateral hemi-tibial tuberosity for treating low-grade recurrent patella dislocation.

PURPOSE: The present study aimed to assess the clinical efficacy and imaging results of reconstruction of the medial patellofemoral ligament through a double bundle of single patellar tract and quadriceps tendons combined with medial displacement of lateral hemi-tibial tuberosity for treating low-grade recurrent patella dislocation. METHODS: Twenty-three patients with recurrent patellar dislocation, including ten males and 13 females, with 23 knee joints were enrolled according to the relevant criteria. Reconstruction of the medial patellofemoral ligament was performed through a double bundle of a single patellar tract and quadriceps tendons combined with medial displacement of lateral hemi-tibial tuberosity. Knee function was evaluated using visual analog scale (VAS) score, International Knee Documentation Committee (IKDC) score, Lysholm score, Tegner score, and Kujala score at pre- and postoperative stages. Patellar stability was assessed by CT scans measuring tibial tuberosity-trochlear groove (TT-TG) distance, lateral patella displacement (LPD), congruence angle (CA), and patellar tilt angle (PTA). RESULTS: All 23 patients were effectively followed up for 13-28 months (mean: 21.91 ± 4.14 months). At the last follow-up, the postoperative VAS score, IKDC score, Lysholm score, Tegner score, and Kujala score of 23 patients were 1.13 ± 0.82, 87.35 ± 3.17, 90.22 ± 1.28, 4.35 ± 0.65, and 89.26 ± 1.96, respectively, as compared to the preoperative values of 5.91 ± 1.13, 30.96 ± 5.09, 30.30 ± 2.98, 1.26 ± 0.62, and 27.87 ± 3.46, respectively, and these differences were statistically significant (P < 0.001). At the last follow-up, the postoperative TT-TG, LPD, CA, and PTA values of the 23 patients were 8.80 ± 1.85 mm, 6.01 ± 1.77 mm, 11.32 ± 6.18°, and 9.35 ± 2.88°, respectively, compared to the preoperative values of 18.77 ± 1.74 mm, 14.90 ± 4.07 mm, 37.82 ± 5.71°, and 23.58 ± 3.24°, respectively, and the differences were statistically significant (P < 0.001). No relevant complications were observed in the 23 patients. CONCLUSIONS: Reconstruction of the medial patellofemoral ligament through a double bundle of a single patellar tract and quadriceps tendons combined with medial displacement of lateral hemi-tibial tuberosity for treating low-grade recurrent patella dislocation showed satisfactory medium-term efficacy, and further investigations are required to confirm the long-term efficacy of this approach.

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes.

A simple and efficient method for the synthesis of spiropyridazine-benzosultams has been developed by means of [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes. This approach displays advantages such as mild reaction conditions, wide substrate range tolerance, simple operation, compatibility with gram-scale preparation.

Pyroptosis by NLRP3/caspase-1/gasdermin-D pathway in synovial tissues of rheumatoid arthritis patients.

We investigated the potential involvement of pyroptosis, a proinflammatory form of regulated cell death, in rheumatoid arthritis (RA). Synovial fluid, synovial tissues and/or serum were compared among 32 patients with RA, 46 patients with osteoarthritis (OA) and 30 healthy controls. Samples were assayed for interleukin (IL)-1ß, IL-18 and lactate hydrogenase (LDH). Synovial expression of NLRP3, caspase-1 and cleaved gasdermin D (GSDMD) was assayed using immunohistochemistry and multiplex immunohistochemistry. Patients with RA showed significantly higher levels of IL-1ß and IL-18 in synovial fluid than patients with OA, and significantly higher levels of both cytokines in serum than healthy controls. RA was associated with higher levels of LDH in synovial fluid than OA. Among patients with RA, levels of IL-1ß, IL-18 and LDH were significantly higher in synovial fluid than in serum, and the levels in synovial fluid positively correlated with disease activity and inflammation. Synovial cells, particularly macrophages, showed upregulation of NLRP3, caspase-1 and cleaved GSDMD in RA compared to OA. Our results implicate pyroptosis in the pathogenesis of RA, perhaps as a driver of local inflammation in joints.

The efficacy and safety of tranexamic acid in rheumatoid arthritis patients undergoing simultaneous bilateral total knee arthroplasty: a multicenter retrospective study.

BACKGROUND: The efficacy and safety of tranexamic acid (TXA) in reducing blood loss following total knee arthroplasty (TKA) in patients with osteoarthritis have been widely confirmed. However, there is still a paucity of the evidences regarding the effectiveness of TXA in patients with rheumatoid arthritis (RA). The purpose of the study is to explore the efficacy and safety of intravenous TXA on blood loss and transfusion risk following simultaneous bilateral TKA (SBTKA) in patients with RA. METHODS: As a multicenter retrospective study, a total of 74 patients diagnosed with RA who underwent SBTKA were assigned into TXA group (15 mg/kg intravenous TXA before skin incision, n = 50) and control group (no TXA use, n = 24). The primary outcomes were total blood loss (TBL) and intraoperative blood loss (IBL). The secondary outcomes were hemoglobin (Hb) and hematocrit (Hct) drop on postoperative day 3, transfusion rate and volume, ambulation time, length of stay, hospitalization expenses and the incidence of complications. RESULTS: The mean TBL, IBL and transfusion volume in TXA group were significantly lower than those in control group. The Hb and Hct drop on postoperative day 3 in control group were higher than those in TXA group (p<0.05). The similar trend was detected on transfusion rate, ambulation time and length of stay. The incidence of complications and hospitalization expenses did not differ significantly between the two groups (p>0.05). CONCLUSIONS: TXA could effectively reduce blood loss, decrease transfusion risk, shorten ambulation time and length of stay following SBTKA in patients with RA, without increasing the risk of complications.

The development of a mouse model to investigate the formation of heterotopic ossification.

BACKGROUND: Muscle injury and concomitant bone injury are important drivers to induce heterotopic ossification (HO). However, the related roles of muscle and concomitant bone injury in HO formation are still unclear. This study aims to develop a mouse model through the combination of hindlimb amputation (Am) and cardiotoxin (CTX) injection to investigate the mechanism of HO formation. METHOD: The mice were randomly divided into Am group (Am of right hindlimb, n = 12), CTX group (CTX injection in the calf muscle of left hindlimb, n = 12) and Am + CTX group (the combination of Am of right hindlimb and CTX injection of left hindlimb, n = 18). MicroCT was used to evaluate the incidence of HO. Histology was used to investigate the progression of HO. RESULTS: The MicroCT showed that only Am or CTX injection failed to induce HO while the combination of Am and CTX injection successfully induced HO. The incidence of HO was significant in Am + CTX group on day 7 (0% vs 0% vs 83.3%, p = 0.001) and day 14 (0% vs 0% vs 83.3%, p = 0.048). HO was located on the left hindlimb where CTX was injected. Moreover, the bone volume and bone density on day 14 were higher than those on day 7 in Am + CTX group. Histology revealed the evidence of calcification and expression of osteogenic markers in calcification sites in Am + CTX group. CONCLUSION: In summary, the combination of Am and CTX injection could successfully induce dystrophic calcification/HO, which occurs in the location of muscle injury.

Pathogenesis of acquired heterotopic ossification: Risk factors, cellular mechanisms, and therapeutic implications.

Heterotopic ossification (HO), including hereditary and acquired HO, is the formation of extraskeletal bone in skeletal muscle and surrounding soft tissues. Acquired HO is often caused by range of motion, explosion injury, nerve injury or burns. Severe HO can lead to pain and limited joint activity, affecting functional rehabilitation and quality of life. Increasing evidence shows that inflammatory processes and mesenchymal stem cells (MSCs) can drive HO. However, explicit knowledge about the specific mechanisms that result in HO and related cell precursors is still limited. Moreover, there are no effective methods to prevent or reduce HO formation. In this review, we provide an update of known risk factors and relevant cellular origins for HO. In particular, we focus on the underlying mechanisms of MSCs in acquired HO, which follow the osteogenic program. We also discuss the latest therapeutic value and implications for acquired HO. Our review highlights the current gaps in knowledge regarding the pathogenesis of acquired HO and identifies potential targets for the prevention and treatment of HO.

Silver Catalyzed Site-Selective C(sp3)-H Bond Amination of Secondary over Primary C(sp3)-H Bonds.

Sulfamates are widespread in numerous pharmacologically active molecules. In this paper, Silver/Bathophenanthroline catalyzed the intramolecular selective amination of primary C(sp3)-H bonds and secondary C(sp3)-H bonds of sulfamate esters, to produce cyclic sulfamates in good yields and with a high site-selectivity. DFT calculations revealed that the interaction between sulfamates and L10 makes the molecule more firmly attached to the catalyst, benefiting the catalysis reaction. The in vitro anticancer activity of the final products was evaluated in MCF-7 breast cancer cells.

Engineering pre-vascularized bone-like tissue from human mesenchymal stem cells through simulating endochondral ossification.

Currently, most in vitro engineered bone tissues do not contain viable blood vessel systems, so the vascularization depends on post-implantation angiogenesis from the host, which is often insufficient for repairing large bone defects. In this study, we aimed to create pre-vascularized bone-like tissue from human bone marrow-derived mesenchymal stem cells (HBMSCs) within the self-generated extracellular matrix by simulating the developmental endochondral ossification. Afterward, a three-dimensional (3D) culture of human umbilical vein endothelial cells (HUVECs)/HBMSCs was introduced to cover bone-like constructs surface for vascularization. Lastly, the pre-vascularized bone-like tissues were subcutaneously implanted into mice and the quality of newly formed blood vessels and bones were later assessed. We particularly examined whether the pre-existing HUVECs/HBMSCs vascular networks within the implants were able to integrate with the host's blood vessels and facilitate bone formation. Our results showed that this developmentally informed procedure resulted in a robust osteogenic differentiation of HBMSCs. Moreover, the bone-like constructs markedly promoted HUVEC/HBMSCs network formation in vitro. After 28 days of implantation in mice, the experimental group, in which bone-like constructs were pre-vascularized with HUVEC/HBMSCs networks, exhibited significantly more functional blood vessels than the control group that contained HUVEC and HBMSC single cells. Interestingly, increased levels of bone formation and absorption markers were also observed in the pre-vascularized bone-like constructs. Taken together, these findings demonstrated the potential of pre-vascularized bone-like constructs in repairing bone defects.

[Research progress of traumatic heterotopic ossification].

Objective: To review and evaluate the research progress of traumatic heterotopic ossification (HO). Methods: The domestic and foreign related research literature on traumatic HO was widely consulted, and its etiology, pathogenesis, pathological progress, diagnosis, prevention, and treatment were summarized. Results: Traumatic HO is often caused by severe trauma such as joint operation, explosion injury, nerve injury, and burn. At present, it is widely believed that the occurrence of traumatic HO is closely related to inflammation and hypoxia. Oral non-steroidal anti-inflammatory drugs and surgery are the main methods to prevent and treat traumatic HO. Conclusion: Nowadays, the pathogenesis of traumatic HO is still unclear, the efficiency of relevant prevention and treatment measures is low, and there is a lack of specific treatment method. In the future, it is necessary to further study the pathogenesis of traumatic HO and find specific prevention and treatment targets.

The use of cell salvage during second-stage reimplantation for the treatment of chronic hip periprosthetic joint infection: a retrospective cohort study.

INTRODUCTION: Given the possibility of inadvertent bacterial contamination of salvaged blood, the use of cell salvage is relatively contraindicated in cases of reimplantation for chronic hip periprosthetic joint infection (PJI). However, there are no published data supporting this assertion. The purpose of the current study was to compare the reinfection rate and rate of postoperative allogeneic blood transfusion (ABT) in second-stage reimplantation for PJI with or without intraoperative cell salvage reinfusion. MATERIALS AND METHODS: We identified 125 patients who underwent two-stage exchange for chronic hip PJI between November 2012 and April 2019. The groups of patients who had (n = 61) and had not (n = 64) received intraoperative cell salvage reinfusion were compared with respect to the curative infection-free rate. Moreover, we compared the need for postoperative ABT and identified independent factors associated with ABT using multiple regression analysis. RESULTS: The log-rank survival curve with an endpoint of infection eradication failure was not significantly different between the cell salvage group (98.4%, 95% CI 95.3-99.9%) and the control group (95.3%, 95% CI 90.2-99.9%) at one year (log rank, P = .330). The rates of postoperative ABT in the cell salvage group were significantly lower than those in the control group (11.5% vs 26.6%, P = .041). In multivariable models, patient age, body mass index, preoperative hemoglobin level, and intraoperative cell salvage were independent predictors of ABT exposure (P < .05). CONCLUSIONS: The use of cell salvage during reimplantation in two-stage exchange for chronic hip PJI did not appear to increase the reinfection rate, while it significantly reduced the rate of postoperative allogeneic red blood transfusion. Greater age, lower BMI, lower preoperative hemoglobin, and non-intraoperative cell salvage reinfusion were associated with higher rate of allogeneic red blood transfusion.

Risk factors of opioid use associated with an enhanced-recovery programme after total knee arthroplasty.

BACKGROUND: Characterizing the impacts of postoperative opioid use on total knee arthroplasty (TKA) patients may help optimize the pain management after TKA. The aim of the study is to examine the prevalence and risk factors for opioid use with an enhanced-recovery programme after primary TKA. METHODS: We identified 361 patients undergoing TKA, and separated those on the basis of whether to receive opioid use after surgery. Themultivariate logistic regression model was used to identify independent risk factors for opioid use after primary TKA. Length of stay (LOS) and postoperative complications were also recorded and compared. RESULTS: The prevalence of opioid use after primary TKA was 23.0%. The significant risk factor was the longer operative time (OR [odds ratio] = 1.017, 95% CI [confidence interval] = 1.001 to 1.032, p = 0.034) and the protective factor was the utilization of tranexamic acid(OR= 0.355, 95% CI = 0.161 to 0.780, p = 0.010). In addition, the LOS was longer in opioid group (p < 0.05). CONCLUSION: Considering the adverse health effects of opioid use, strategies need to be developed to prevent persistent opioid use after TKA. Reducing operative time and the application of tranexamic acid could lower the risk of opioid use with an enhanced-recovery programme after primary TKA.

The effect of body mass index on blood loss and complications in simultaneous bilateral total hip arthroplasty: A multicenter retrospective study.

BACKGROUND: The effect of body mass index (BMI) on blood loss in simultaneous bilateral total hip arthroplasty (SBTHA) was still undetermined. The purpose of the study was to evaluate the blood loss, transfusion and incidence of complications in normal, overweight, and obese patients undergoing SBTHA. METHODS: A total of 344 patients following SBTHA were enrolled into this study. The patients were assigned into three groups on the basis of their BMI, including normal (BMI 18.0-24.9 kg/ m2), overweight (BMI 25.0-29.9 kg/ m2), or obese group (BMI ≥ 30.0 kg/ m2). The primary outcome was total blood loss (TBL), and secondary outcomes were intraoperative blood loss, drain volume, ratio of TBL and patient's blood volume (PBV), transfusion rate and volume, hemoglobin and hematocrit drop, length of stay, expenses, and complications. RESULTS: The PBV and TBL increased significantly along with the elevated BMI (p < 0.001; p = 0.019, respectively). There was no significant difference in intraoperative blood loss, drain volume, transfusion volume, length of stay, expenses, or incidence of complications among the three groups. In addition, the transfusion rate in normal group was higher than that in overweight (58.3% vs 39.6%, p = 0.001) and obese group (58.3% vs 31.9%, p = 0.001). The maximum hemoglobin drop in obese group was the highest (p = 0.001). CONCLUSION: Obesity could increase perioperative blood loss but not increase transfusion risk in the setting of SBTHA. Conversely, obese and overweight patients maybe have lower transfusion need compared with normal patients because of more blood volume. In addition, obesity did not affect the incidence of complications.

Performance of Self-Healing Cementitious Composites Using Aligned Tubular Healing Fiber.

From the perspective of improving the self-healing method in construction, a tubular healing fiber was adopted as a container to improve the encapsulation capacity, which was available using a micro-capsule as a container. Knowing the direction of the stresses to which structure members are subjected, this research investigated the influence of aligning tubular healing fibers parallel to intended stress into a cementitious composite to increase the self-healing capability. For that, a healing agent was encapsulated into a tubular healing fiber made with polyvinylidene of fluoride resin (PVDF). Then, the healing fiber was combined with steel fibers to align both fibers together parallel to the direction of an intended splitting tensile stress when subjected to a magnetic field in a cylindrical cementitious composite. The alignment method and the key point through which the alignment of the healing fibers could efficiently improve autonomic self-healing were investigated. Since the magnetic field is known to be able to drag steel to an expected direction, steel fibers were combined with the healing fibers to form a hybrid fiber that aligned both fibers together. The required mixture workability was investigated to avoid the sinking of the healing fibers into the mixture. The healing efficiency, according to the orientation of the healing fibers in the composite matrix, was evaluated through a permeability test and a repetitive splitting tensile test. The aligned healing fibers performed better than the randomly distributed healing fibers. However, according to the healing efficiency with aligned healing fibers, it was deduced that the observed decreasing effect of the container's alignment on the specimen's mechanical properties was low enough to be neglected.

Association between preoperative hemoglobin and postoperative moderate and severe anemia among patients undergoing primary total knee arthroplasty: a single-center retrospective study.

BACKGROUND: Postoperative moderate and severe anemia (PMSA) has been a serious perioperative complication in primary total knee arthroplasty (TKA). However, the ideal cutoff values to predict PMSA is still undetermined. The aim of this study was (1) to identify the risk factors associated with PMSA and (2) to establish the cutoff values of preoperative hemoglobin (HB) associated with increased PMSA in primary TKA. METHODS: We identified 474 patients undergoing primary TKA and separated those in which PMSA (HB was less than 110 g/L on postoperative day 1 and 3) was developed from those without PMSA. Multivariate logistic regression model was used to identify independent risk factors for PMSA. Area under the receiver-operator curve (AUC) was used to determine the best-supported preoperative HB cutoff across all the patients. RESULTS: The PMSA rate in primary TKA was 53.2%. Significant risk factors were lower preoperative HB (OR [odds ratio] = 1.138, 95% CI [confidence interval] = 1.107-1.170, p < 0.001) and more intraoperative blood loss (OR = 1.022, 95% CI 1.484-4.598, p < 0.001). A preoperative HB cutoff value that maximized the AUC was 138.5 g/L for men (sensitivity: 79.4%, specificity: 75.0%) and 131.5 g/L for women (sensitivity: 74.7%, specificity: 80.5%), respectively. CONCLUSION: We should recognize and consider the related risk factors to establish specific, personalized risk assessment for PMSA, including preoperative HB and intraoperative blood loss. Of these, preoperative HB was a referable tool to predict PMSA in primary TKA.

Graphene oxide-functionalized nanocomposites promote osteogenesis of human mesenchymal stem cells via enhancement of BMP-SMAD1/5 signaling pathway.

Biomaterials that can harness the intrinsic osteogenic potential of stem cells offer a promising strategy to accelerate bone regeneration and repair. Previously, we had used methacrylated gelatin (GelMA)-based scaffolds to achieve bone formation from human mesenchymal stem cells (hMSCs). In this study, we aimed to further enhance hMSC osteogenesis by incorporating graphene oxide (GO)-based nanosheets into GelMA. In vitro results showed high viability and metabolic activities in hMSCs encapsulated in the newly developed nanocomposites. Incorporation of GO markedly increased mineralization within hMSC-laden constructs, which was further increased by replacing GO with silica-coated graphene oxide (SiGO). Mechanistic analysis revealed that the nanosheet enhanced the production, retention, and biological activity of endogenous bone morphogenetic proteins (BMPs), resulting in robust osteogenesis in the absence of exogenous osteoinductive growth factors. Specifically, the osteoinductive effect of the nanosheets was abolished by inhibiting the BMP signaling pathway with LDN-193189 treatment. The bone formation potential of the technology was further tested in vivo using a mouse subcutaneous implantation model, where hMSCs-laden GO/GelMA and SiGO/GelMA samples resulted in bone volumes 108 and 385 times larger, respectively, than the GelMA control group. Taken together, these results demonstrate the biological activity and mechanism of action of GO-based nanosheets in augmenting the osteogenic capability of hMSCs, and highlights the potential of leveraging nanomaterials such as GO and SiGO for bone tissue engineering applications.

Six-Dose Intravenous Tranexamic Acid Regimen Further Inhibits Postoperative Fibrinolysis and Reduces Hidden Blood Loss following Total Knee Arthroplasty.

There is no consensus regarding the ideal dosages and times of multiple-dose intravenous tranexamic acid (IV-TXA) administration in total knee arthroplasty (TKA). This study aimed to assess the effect of six-dose IV-TXA with the total dosage more than 6 g on postoperative fibrinolysis and hidden blood loss (HBL) after primary TKA. A total of 175 patients were randomized into three groups to receive placebo (group A), or a single preoperative dose of 20 mg/kg IV-TXA (group B), or six-dose IV-TXA from the beginning of the procedure to subsequent 24 hours with the total dosage more than 6 g (group C). The calculated HBL, maximum hemoglobin (Hb) drop, transfusion rate, and the incidence of thromboembolic events were compared among groups. The levels of fibrinolysis parameters in plasma including fibrin(-ogen) degradation products (FDP) and D-dimer were measured at six time points from preoperatively to 3-month postoperative period. The mean HBL and maximum Hb drop in group C (515.51 ± 245.79 mL, and 2.06 ± 0.73 g/dL, respectively) were significantly lower than those in groups B (756.06 ± 226.79 mL, p < 0.001; and 2.77 ± 0.78 g/dL, p < 0.001, respectively) and A (987.65 ± 275.38 mL, p < 0.001; and 3.49 ± 0.86 g/dL, p < 0.001, respectively). Such differences were also detected between groups A and B (p < 0.001 and p < 0.001, respectively). The levels of FDP and D-dimer in plasma were lower in group C than those in groups B and A on postoperative 24, 48, 72 hours (p < 0.001 for all). No episode of transfusion occurred, and the incidence of thromboembolic events were similar among groups (p > 0.05). The administration of six-dose IV-TXA during the first 24 hours resulted in reduced HBL following TKA without a measured increase in thromboembolic events.

Efficacy and safety of intrawound vancomycin in primary hip and knee arthroplasty.

AIMS: The efficacy and safety of intrawound vancomycin for preventing surgical site infection in primary hip and knee arthroplasty is uncertain. METHODS: A systematic review of the literature was conducted, indexed from inception to March 2020 in PubMed, Web of Science, Cochrane Library, Embase, and Google Scholar databases. All studies evaluating the efficacy and/or safety of intrawound vancomycin in patients who underwent primary hip and knee arthroplasty were included. Incidence of periprosthetic joint infection (PJI), superficial infection, aseptic wound complications, acute kidney injury, anaphylactic reaction, and ototoxicity were meta-analyzed. Results were reported as odds ratios (ORs) and 95% confidence intervals (CIs). The quality of included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) assessment tool. RESULTS: Nine studies involving 4,607 patients were included. Intrawound vancomycin was associated with lower incidence of PJI (30 patients (1.20%) vs 58 control patients (2.75%); OR 0.44, 95% CI 0.28 to 0.69) and simultaneous acute kidney injury (four patients (0.28%) vs four control patients (0.35%), OR 0.71, 95% CI 0.19 to 2.55). However, it did not reduce risk of superficial infection (four patients (0.67%) vs six control patients (1.60%), OR 0.60, 95% CI 0.17 to 2.12) and was associated with higher incidence of aseptic wound complications (23 patients (2.15%) vs eight in control patients (0.96%), OR 2.39, 95% CI 1.09 to 5.23). Four studies reported no anaphylactic reactions and three studies reported no ototoxicity in any patient group. CONCLUSION: The current literature suggests that intrawound vancomycin used in primary hip and knee arthroplasty may reduce incidence of PJI, but it may also increase risk of aseptic wound complications. Cite this article: Bone Joint Res 2020;9(11):778-788.

Dead muscle tissue promotes dystrophic calcification by lowering circulating TGF-ß1 level.

AIMS: Dystrophic calcification (DC) is the abnormal appearance of calcified deposits in degenerating tissue, often associated with injury. Extensive DC can lead to heterotopic ossification (HO), a pathological condition of ectopic bone formation. The highest rate of HO was found in combat-related blast injuries, a polytrauma condition with severe muscle injury. It has been noted that the incidence of HO significantly increased in the residual limbs of combat-injured patients if the final amputation was performed within the zone of injury compared to that which was proximal to the zone of injury. While aggressive limb salvage strategies may maximize the function of the residual limb, they may increase the possibility of retaining non-viable muscle tissue inside the body. In this study, we hypothesized that residual dead muscle tissue at the zone of injury could promote HO formation. METHODS: We tested the hypothesis by investigating the cellular and molecular consequences of implanting devitalized muscle tissue into mouse muscle pouch in the presence of muscle injury induced by cardiotoxin. RESULTS: Our findings showed that the presence of devitalized muscle tissue could cause a systemic decrease in circulating transforming growth factor-beta 1 (TGF-ß1), which promoted DC formation following muscle injury. We further demonstrated that suppression of TGF-ß signalling promoted DC in vivo, and potentiated osteogenic differentiation of muscle-derived stromal cells in vitro. CONCLUSION: Taken together, these findings suggest that TGF-ß1 may play a protective role in dead muscle tissue-induced DC, which is relevant to understanding the pathogenesis of post-traumatic HO. Cite this article: Bone Joint Res 2020;9(11):742-750.

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.

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.