The endoplasmic reticulum stress-autophagy pathway is involved in apelin-13-induced cardiomyocyte hypertrophy in vitro.

Apelin is the endogenous ligand for the G protein-coupled receptor APJ, and plays important roles in the cardiovascular system. Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway. The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro. Treatment of H9c2 cells with apelin-13 (0.001-2 µmol/L) dose-dependently increased the production of ROS and the expression levels of NADPH oxidase 4 (NOX4). Knockdown of Nox4 with siRNAs effectively prevented the reduction of GSH/GSSG ratio in apelin-13-treated cells. Furthermore, apelin-13 treatment dose-dependently increased the expression of Bip and CHOP, two ER stress markers, in the cells. Knockdown of APJ or Nox4 with the corresponding siRNAs, or application of NADPH inhibitor DPI blocked apelin-13-induced increases in Bip and CHOP expression. Moreover, apelin-13 treatment increased the formation of autophagosome and ER fragments and the LC3 puncta in the ER of the cells. Knockdown of APJ, Nox4, Bip or CHOP with the corresponding siRNAs, or application of DPI or salubrinal attenuated apelin-13-induced overexpression of LC3-II/I and beclin 1. Finally, knockdown of Nox4, Bip or CHOP with the corresponding siRNAs, or application of salubrinal significantly suppressed apelin-13-induced increases in the cell diameter, volume and protein contents. Our results demonstrate that ER stress-autophagy is involved in apelin-13-induced H9c2 cell hypertrophy.

[Management of femoral neck fracture post total knee arthroplasty].

OBJECTIVE: To investigate the risk factors, management and prognosis of femoral neck fracture post total knee arthroplasty (TKA). METHODS: From January 2003 to August 2009, 45 cases of femoral neck fracture post TKA were treated. There were 8 males and 37 females with an age range of 56 - 81 years old. Among them, there were ipsilateral (n = 36) and contralateral (n = 9) femoral neck fractures. Due to the fracture site and type, the treatment plans were formulated. And a follow-up was conducted to record the Harris hip score and complications. RESULTS: The incidence of femoral neck fracture following TKA and osteoporosis had a linear correlation. And the fracture rate increased with the aggravation of osteoporosis. The stability of ipsilateral fracture group was lower than those of contralateral fracture and no fracture groups. Except for 4 mortality cases, 41 patients were followed up for 2 to 7 years with an average period of 3.6 years. There were 12 patients in the cannulated screw fixation group. The outcomes were fracture healing (n = 5) and femoral head necrosis (n = 7). Twenty-five cases underwent femoral head replacement. And 3 died and second fracture occurred in 3 cases. Eight cases underwent total hip arthroplasty. And 1 died and there was 1 case of second fracture. The Harris scores of the cannulated screw fixation group was significantly lower than the hip replacement groups (q test, P < 0.05). COMPLICATIONS: After internal fixation, 7 cases suffered femoral head necrosis and underwent femoral head replacement. And secondary fractures after hip replacement occurred in 4 cases and they were treated by plate and cable or LISS (less invasive stabilization system) system. CONCLUSION: Femoral neck fracture following TKA is usually caused by a low-energy injury. Osteoporosis is one of its high-risk factors. Knee instability is associated with ipsilateral femoral neck fracture. Clinically it can be treated by internal fixation or hip arthroplasty. And internal fixation of femoral neck fracture frequently induces femoral head necrosis. And femoral head replacement is applicable.

Postoperative Bone Marrow Lesions (BMLs) Are Associated with Pain Severity in Patients Undergoing Open Wedge High Tibial Osteotomy (OWHTO).

The purpose of the study was to investigate the relationship between postoperative bone marrow lesions (BMLs) and pain severity in patients undergoing open wedge high tibial osteotomy (OWHTO). We reviewed the patients undergoing OWHTO between April 2018 and April 2020. The demographic and clinical data of patients were collected. Clinically, VAS and Knee injury and Osteoarthritis Outcome Score (KOOS) were used to assess pain level and functional outcomes of patients. The MRI Osteoarthritis Knee Score (MOAKS) was used to assess the total BMLs size in medial tibiofemoral (MTF), lateral tibiofemoral (LTF), and patellofemoral (PF) joints. 98 patients were enrolled in the study, including 57 male and 41 female patients. The VAS scores improved significantly from 6.1 ± 0.8 to 1.5 ± 0.9 (p < 0.001), and all subscales of KOOS improved significantly after surgery (p < 0.001). There were no significant differences between the pre- and postoperative total BML size of PF and LTF joints (p > 0.05). We observed significant improvements in the total BML size of MTF joint (p < 0.001). The VAS scores and KOOS pain scores improved better in patients without postoperative MTF joint BMLs (p < 0.001). Postoperative MTF joint BMLs were correlated with postoperative VAS (p < 0.001) and KOOS pain (p < 0.001). Our study demonstrates that MTF joint BMLs improved significantly after OWTHO. We confirmed that the presence of postoperative MTF joint BMLs are strongly associated with pain severity. The greater the improvement in postoperative MTF joint BMLs, the less pain. Our findings provide valuable understandings of OWHTO in the treatment of knee osteoarthritis (KOA) and potential future directions for KOA treatment approaches.

A Novel Application of Unsupervised Machine Learning and Supervised Machine Learning-Derived Radiomics in Anterior Cruciate Ligament Rupture.

PURPOSE: We aim to present an unsupervised machine learning application in anterior cruciate ligament (ACL) rupture and evaluate whether supervised machine learning-derived radiomics features enable prediction of ACL rupture accurately. PATIENTS AND METHODS: Sixty-eight patients were reviewed. Their demographic features were recorded, radiomics features were extracted, and the input dataset was defined as a collection of demographic features and radiomics features. The input dataset was automatically classified by the unsupervised machine learning algorithm. Then, we used a supervised machine learning algorithm to construct a radiomics model. The t-test and least absolute shrinkage and selection operator (LASSO) method were used for feature selection, random forest and support vector machine (SVM) were used as machine learning classifiers. For each model, the sensitivity, specificity, accuracy, and the area under the curve (AUC) of receiver operating characteristic (ROC) curves were calculated to evaluate model performance. RESULTS: In total, 5 demographic features were recorded and 106 radiomics features were extracted. By applying the unsupervised machine learning algorithm, patients were divided into 5 groups. Group 5 had the highest incidence of ACL rupture and left knee involvement. There were significant differences in left knee involvement among the groups. Forty-three radiomics features were extracted using t-test and 7 radiomics features were extracted using LASSO method. We found that the combination of LASSO selection method and random forest classifier has the highest sensitivity, specificity, accuracy, and AUC. The 7 radiomics features extracted by LASSO method were potential predictors for ACL rupture. CONCLUSION: We validated the clinical application of unsupervised machine learning involving ACL rupture. Moreover, we found 7 radiomics features which were potential predictors for ACL rupture. The study indicated that radiomics could be a valuable method in the prediction of ACL rupture.

Unsupervised Machine Learning-Based Analysis of Clinical Features, Bone Mineral Density Features and Medical Care Costs of Rotator Cuff Tears.

PURPOSE: We aim to present unsupervised machine learning-based analysis of clinical features, bone mineral density (BMD) features, and medical care costs of Rotator cuff tears (RCT). PATIENTS AND METHODS: Fifty-three patients with RCT were reviewed, the clinical features, BMD features, and medical care costs were collected and analyzed by descriptive statistics. Furtherly, unsupervised machine learning (UML) algorithm was used for dimensionality reduction and cluster analysis of the RCT data. RESULTS: There were 26 males and 27 females. The patients were divided into four subgroups using the UML algorithm. There were significant differences among four subgroups regarding trauma exposure, full-thickness supraspinatus tendon tears, infraspinatus tendon tear, subscapularis tendon tear, BMD distribution, medial row anchors, lateral row anchors, total medical care costs, and consumables costs. We observed the highest frequency of trauma exposure, infraspinatus tendon tear, subscapularis tendon tear, osteoporosis, the highest number of medial row anchors, lateral row anchors, total medical care costs, and consumables costs in subgroup II. CONCLUSION: The unsupervised machine learning-based analysis of RCT can provide clinically meaningful classification, which shows good interpretability and contribute to a better understanding of RCT. The significance of the results is limited due to the small number of samples, a larger follow-up study is needed to confirm the encouraging results.

Comparison between oral and intravenous application of tranexamic acid for total hip arthroplasty: a meta-analysis.

AIM: We conducted a meta-analysis to compare the efficacy and safety of oral and intravenous applications of tranexamic acid (TXA) in total hip arthroplasty (THA). MATERIALS & METHODS: Electronic databases, including PubMed, Cochrane CENTRAL, ScienceDirect and Embase, were searched to identify the studies comparing the efficacy and safety of oral and intravenous applications of TXA in THA. Relevant journals and conference proceedings were manually searched. The pooled data were analyzed using RevMan 5.1. RESULTS: Four randomized control trials and one retrospective study were identified. A meta-analysis showed no significant differences in hemoglobin reduction, total blood loss and transfusion requirements. CONCLUSION: Oral applications of TXA are comparable to intravenous applications of TXA in primary unilateral THA for blood conservation and cost-saving measures.

Hybrid graft vs autograft in anterior cruciate ligament reconstruction: a meta-analysis.

PURPOSE: We conducted this meta-analysis to evaluate the efficacy of hybrid grafts in anterior cruciate ligament reconstruction (ACLR). METHODS: We performed an electronic search of the Cochrane Library, PubMed, Embase, and ScienceDirect from the inception of these databases to February 2018, based on the terms "anterior cruciate ligament or ACL reconstruction", "autograft", "hybrid", and "augment". Relevant journals and conference proceedings were searched manually. Quality assessment, data extraction, and calculation of data from the included studies were conducted independently by two reviewers using RevMan 5.1. RESULTS: One randomized controlled trial and eight nonrandomized controlled trials met inclusion criteria. Larger graft diameters were found in the hybrid-graft group (mean difference -1.47, P=0.0001). There was no significant difference in failure rate (OR 2.13, P=0.21), retearing (OR 2.23, P=0.12), revision of ACLR (OR 1.05, P=0.87) or reoperation (OR 1.27, P=0.35). Subgroup analysis showed that hybrid-graft patients with meniscus injury suffered more revision (OR 4.10, P=0.02) and reoperation (OR 5.74, P=0.001). Both autografts and hybrid grafts performed similarly in most knee-score systems. However, autograft patients had better KT-1000 (mean difference 0.24, P=0.05) and quality-of-life results on the Knee Injury and Osteoarthritis Outcome Score measure (mean difference 7.23, P=0.05). CONCLUSION: This meta-analysis of the current literature indicates similar performance of hybrid or autologous grafts in ACLR, though hybrid grafts had larger diameters than autografts. Other potential factors to influence failure, revision, or postoperative knee function, such as irradiation, age at reconstruction, meniscus injury/treatment, and hybrid-graft remodeling, should be investigated further.

Negative pressure wound therapy in total hip and knee arthroplasty: a meta-analysis.

Aim: To assess the efficiency and safety of negative pressure wound therapy (NPWT) in the total hip and knee arthroplasty, we conducted a meta-analysis from randomized controlled trials. Methods: Potential academic articles were identified from the Cochrane Library, PubMed, Embase, Springer and ScienceDirect. Secondary sources were identified from the references of the included literature. RevMan 5.1 was used to analyze the pooled data. Results: Six randomized controlled trials met the inclusion criteria. Meta-analysis showed more superficial surgical site infection and blisters in patients with total knee arthroplasty. There were no significant differences between two groups in total infection and total complications. Conclusion: NPWT decreased the incidence of superficial surgical site infection. More blisters were noticed in patients with NPWT after total knee arthroplasty.

Baicalin Attenuates Joint Pain and Muscle Dysfunction by Inhibiting Muscular Oxidative Stress in an Experimental Osteoarthritis Rat Model.

Osteoarthritis (OA) is the most common degenerative joint disease, and causes major pain and disability in adults. It has been reported that muscle weakness and inflammation contribute to osteoarthritis development and progression. Oxidative stress plays important roles in muscle dysfunction and inflammation in osteomyelitis. Baicalin, the major active constituent of the isolated root of Scutellarialateriflora Georgi, has been shown to have anti-oxidative and anti-inflammatory effects. In this study, we evaluated the potential effects of baicalin on osteoarthritis. We established experimental osteoarthritis rat model, applied baicalin to the rats, and then explored the potential protective effect of baicalin on osteoarthritis severity, muscle dysfunction, and oxidative stress. Baicalin alleviated severity of OA in rats. Baicalin application attenuated muscle dysfunction in OA rats by increasing citrate synthase activity, myosin heavy chain IIa expression, and decreasing interleukin 6 production. Baicalin decreased muscular reactive oxygen species generation in OA rats. Baicalin inhibited nuclear factor erythroid-derived 2-like 2 expression in OA rats. Baicalin attenuated osteoarthritis in rat by inhibiting oxidative stress.

Risk Factors Comparison for Radial and Horizontal Tears.

Tears in posterior horn of medial meniscus mainly included horizontal tear, transversal tear, radial tear, complex tear, and bucket handle tear. We analyzed and compared the risk factors for radial tear and horizontal tear in the posterior horn of medial meniscus. A total of 407 consecutive cases who received arthroscopic treatment of medial meniscus tears were analyzed retrospectively. Among them, 103 cases were radial tear in posterior horn of medial meniscus and 107 were horizontal tear. Clinical data records included patients' age, gender, duration of symptoms, body mass index, trauma history, and slope angle of tibia, valgus angle of knee, and grading of cartilage (Outerbridge Grades) were collected and analyzed. In addition, multiple-factor nonconditional logistic regression was adopted to analyze the related risk factors in these two types of medial meniscus tears. The two groups have no difference in age, trauma history, slope angle of tibia, and duration of symptoms but have significant difference in gender, body mass index, and valgus angle of knee and grading of cartilage. Multiple factors analysis indicated that valgus angle, age, and grading of cartilage were risk factors in medial meniscus tears. Patients with posterior horn tear in medial meniscus have higher incidence among senile osteoarthritis, while radial tear was more likely to occur in elderly patients with knee-joint varus and serious cartilage degeneration.

[DEVELOPMENT RESEARCH OF PREVENTION OF PROSTHETIC JOINT INFECTION].

OBJECTIVE: To summarize the recent progress in prevention of prosthetic joint infection (PJI) so as to provide clinical references. METHODS: The publications concerning the etiology and surgical management of PJI were reviewed, analyzed, and summarized. RESULTS: The prevention of PJI is related to preoperative, intraoperative, and postoperative aspects of PJI, comprehensive treatment is considered to be the most common method for PJI. CONCLUSION: These prevention strategies that may be utilized in all phases of perioperative care, a multifaceted approach to the patient undergoing total joint replacement will have the greatest positive effect.

The use of clamped drainage to reduce blood loss in total hip arthroplasty.

BACKGROUND: Drainage is a routine practice used to reduce hematoma and blood loss following total hip arthroplasty. The aim of this study was to assess the effect of clamped drainage on blood loss and wound healing after total hip arthroplasty. METHODS: A prospective cohort of 44 patients with hip osteoarthritis or femur head necrosis undergoing total hip arthroplasty was randomized equally into two groups: 6-h postoperative clamped or non-clamped suction tube drainage. Body mass index, gender distribution, preoperative hemoglobin, hip pathology, and affected side were comparable between the two groups. Blood loss, hemoglobin levels, and wound healing complications were recorded and compared between groups. RESULTS: The drainage blood loss and calculated blood loss volumes were higher for the non-clamped group. About 100 mL more blood loss was noticed in the non-clamped group. There was no significant difference in adverse events or need for transfusion. CONCLUSIONS: The present study showed a statistically significant reduction in postoperative drainage amount between clamped and unclamped drainage groups, but this difference was not large enough to warrant increased blood transfusion requirements in patients with unclamped drainage. Further studies are essential to define the critical period of clamping that is compatible with the dual objectives of reduced blood loss and lack of wound complications from hematoma.

Effects of knee position on blood loss following total knee arthroplasty: a randomized, controlled study.

OBJECTIVE: Blood loss following total knee arthroplasty is a serious side-effect of surgery and impacts on patient recovery and quality of life. The aim of this study was to assess the effect of postoperative knee position during recovery on blood loss and range of motion. METHODS: One hundred consecutive patients, with stage III or IV degenerative osteoarthritis, were enrolled in the study and randomized equally between two treatment groups: flexion and extension. In the flexion group, the affected leg was elevated postoperatively by 45° at the hip, with 45° flexion at the knee, while patients in the extension group had the knee extended fully. Blood loss, pre- and postoperative hemoglobin levels, and range of motion were recorded together with duration of hospital stay and complications. RESULTS: Calculated blood loss, hidden blood loss, and postoperative hemoglobin levels between the two groups were significantly different, with patients in the flexion group experiencing lower blood loss than those in the extension group (P < 0.05). After 6-week rehabilitation, patients from both groups attained a similar range of motion in the joint. Duration of hospital stay was shorter in the flexion group by 1.6 days. Wound infection rates were similar in both groups, and we observed no proven deep vein thrombosis. CONCLUSIONS: Postoperative elevation of the hip by 45°, with 45° knee flexion, is an effective and simple method of reducing blood loss and hospital stay following unilateral primary total knee arthroplasty.

Safety and efficacy of intra-articular tranexamic acid injection without drainage on blood loss in total knee arthroplasty: A randomized clinical trial.

BACKGROUND: Major blood loss is unavoidable after primary total knee arthroplasty (TKA). The aim of this study was to determine if tranexamic acid (TXA) can reduce major blood loss following TKA. METHODS: In this double-blind, randomized, placebo-control trial, 60 patients treated with unilateral primary cement TKA between August 1st 2013 and September 30th 2013 were randomized into TXA 500 mg intra-articular injection without drainage (test group, 30 knees) and 30 patients with saline intra-articular injection (control group, 30 knees). RESULTS: There was a significant reduction in mean blood loss (560.55 mL) between the groups at postoperative day (POD) 5 (999.22 mL vs. 1559.77 mL, P = 0.001). The maximum hemoglobin drop was identified at POD 3 (10.51 g/dL vs. 9.10 g/dL, mean difference = 1.41 g/dL). Also, there was a significant reduction in red blood cell and hematocrit loss (P = 0.001). The transfusion rates (0% vs. 23.3%, P = 0.011) and average amount transfused (0.00 ± 0.00 units vs. 0.53 ± 1.04 units, P = 0.009) were significantly lower in the TXA group compared with control group. No significant difference in coagulation marker changes were found between TXA and control groups (P > 0.05), but the D-dimer levels at 3 and 5 days post-TKA were statistically lower in the TXA group (P < 0.05). No significant changes in the rate of symptomatic deep venous thrombosis, pulmonary embolism, or wound healing problems were noted. CONCLUSIONS: TXA treatment without drainage during TKA reduces the amount of blood transfusions required without increasing the rate of adverse events.

Effect of fibrin sealant on blood loss following total knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: A systematic review of randomized controlled trials was conducted to examine the efficacy of fibrin sealants for the reduction of postoperative blood loss and allogeneic red blood cell transfusion in total knee arthroplasty (TKA). METHODS: Studies published through May 2013 were identified from PubMed, Embase, the Cochrane library, ScienceDirect, and other databases. Two independent reviewers assessed the quality of methodology using the Grade of Recommendations Assessment, Development and Evaluation approach and extracted data from literature. The mean difference (MD) of blood loss, hemoglobin loss, and risk ratios (RR) of transfusion rate and adverse events in the fibrin-treated and placebo groups were pooled throughout the study. The relevant data were analyzed using Stata 11.0 software. RESULTS: Eight studies were included in the review, with a total sample size of 558 patients. The drainage blood loss [MD = -354.02 mL, 95% confidence interval (CI) (-500.87 to -207.18); P < 0.05], reduction in calculated total blood loss [MD = -402.12, 95% CI (-599.16 to -205.08); P < 0.05], hemoglobin loss [MD = -0.86 g/dL, 95% CI (-1.10 g/dL to -0.61 g/dL); P < 0.05], and transfusion rate [RR = 0.62, 95% CI (0.45-0.86); P < 0.05] were all significantly reduced following treatment with fibrin sealants. There were no significant differences in the incidence of adverse events [RR = 0.69, 95% CI (0.32-1.59); P > 0.05] among the study groups. CONCLUSIONS: The results of the present meta-analysis suggest that fibrin sealants for patients undergoing TKA may reduce blood loss and maintain higher hemoglobin levels, particularly when fibrin sealants are used at higher dosage. Furthermore, fibrin sealants do not increase the risk of postoperative deep vein thrombosis, superficial infection, pulmonary embolism, and hematoma. Further evaluation is required to confirm our findings before fibrin sealants can be used in patients undergoing TKA. LEVEL OF EVIDENCE: II.