miR-486-5p Attenuates Steroid-Induced Adipogenesis and Osteonecrosis of the Femoral Head Via TBX2/P21 Axis.

Enhanced adipogenic differentiation of mesenchymal stem cells (MSCs) is considered as a major risk factor for steroid-induced osteonecrosis of the femoral head (SOFNH). The role of microRNAs during this process has sparked interest. miR-486-5p expression was down-regulated significantly in femoral head bone tissues of both SONFH patients and rat models. The purpose of this study was to reveal the role of miR-486-5p on MSCs adipogenesis and SONFH progression. The present study showed that miR-486-5p could significantly inhibit adipogenesis of 3T3-L1 cells by suppressing mitotic clonal expansion (MCE). And upregulated expression of P21, which was caused by miR-486-5p mediated TBX2 decrease, was responsible for inhibited MCE. Further, miR-486-5p was demonstrated to effectively inhibit steroid-induced fat formation in the femoral head and prevented SONFH progression in a rat model. Considering the potent effects of miR-486-5p on attenuating adipogenesis, it seems to be a promising target for the treatment of SONFH.

Qualitative Histopathological Classification of Primary Bone Tumors Using Deep Learning: A Pilot Study.

BACKGROUND: Histopathological diagnosis of bone tumors is challenging for pathologists. We aim to classify bone tumors histopathologically in terms of aggressiveness using deep learning (DL) and compare performance with pathologists. METHODS: A total of 427 pathological slides of bone tumors were produced and scanned as whole slide imaging (WSI). Tumor area of WSI was annotated by pathologists and cropped into 716,838 image patches of 256 × 256 pixels for training. After six DL models were trained and validated in patch level, performance was evaluated on testing dataset for binary classification (benign vs. non-benign) and ternary classification (benign vs. intermediate vs. malignant) in patch-level and slide-level prediction. The performance of four pathologists with different experiences was compared to the best-performing models. The gradient-weighted class activation mapping was used to visualize patch's important area. RESULTS: VGG-16 and Inception V3 performed better than other models in patch-level binary and ternary classification. For slide-level prediction, VGG-16 and Inception V3 had area under curve of 0.962 and 0.971 for binary classification and Cohen's kappa score (CKS) of 0.731 and 0.802 for ternary classification. The senior pathologist had CKS of 0.685 comparable to both models (p = 0.688 and p = 0.287) while attending and junior pathologists showed lower CKS than the best model (each p < 0.05). Visualization showed that the DL model depended on pathological features to make predictions. CONCLUSION: DL can effectively classify bone tumors histopathologically in terms of aggressiveness with performance similar to senior pathologists. Our results are promising and would help expedite the future application of DL-assisted histopathological diagnosis for bone tumors.

Value of passive anterior tibial subluxation on axial MRI in identifying anterior cruciate ligament functional deficiency in patients with advanced anteromedial osteoarthritis of the knee: a case-control study.

BACKGROUND: A functionally deficient anterior cruciate ligament (ACL) is considered one of the contraindications in unicompartmental knee arthroplasty (UKA). But there is still a lack of standardized and reproducible methods to assess ACL functional integrity in patients with advanced anteromedial osteoarthritis of the knee (AMOA). This study explores the value of passive anterior tibial subluxation (PATS) on axial MRI in evaluating ACL status in this population. METHODS: Patients who met UKA indications between November 2017 and September 2020 were included and grouped into "intact" (ACLI) or "deficient" (ACLD) group according to their ACL status during surgery. All participants underwent MRI with a standardized protocol. The measurements of medial and lateral PATS were conducted on axial MRI, and the mean of them was calculated as global PATS. Then the reliability and diagnostic ability of PATS were determined. RESULTS: A total of 85 patients (45 for ACLI group, 40 for ACLD group) were included after selection. The measurements of PATS showed excellent intra- and inter-observer reliabilities (with an intraclass correlation coefficient of at least 0.986). The global PATS of the ACLI group was significantly lower than that of the ACLD group (- 2.30 ± 1.96 vs. 1.03 ± 1.96 mm, P<0.0001). The diagnostic ability of global PATS was good (area under the curve = 0.897), and a threshold of 1.2 mm had a specificity of 100%, a sensitivity of 55%, and an accuracy of 78.82%. CONCLUSION: An axial global PATS of 1.2 mm on MRI is greatly specific for identifying a functionally deficient ACL in patients with advanced AMOA.

Prevalence and Risk Factors of Osteoporosis in Chinese Postmenopausal Women Awaiting Total Knee Arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) complications associated with low bone quality are challenging for orthopaedic surgeons to treat, but little is known about bone quality in Chinese postmenopausal women awaiting TKA. This study investigated the incidence of osteoporosis (OP) and explored the preoperative risk factors for OP in this population. METHODS: We retrospectively reviewed the data of Chinese postmenopausal women who were indicated for TKA between May 2017 and June 2020. The bone mineral density (BMD) of the hip and lumbar spine and multiple preoperative parameters were collected and analyzed. Binary logistic regression analysis was performed to identify independent risk factors for OP in this population. RESULTS: A total of 204 postmenopausal women with advanced knee OA were included in the study (age: 69.7±8.5 years; body mass index [BMI]: 25.5±4.0 kg/m2). The OP prevalence among all participants was 59.8%, and the patients aged 60-80 years had a significantly lower BMD than did the age/ethnicity-adjusted population. An age ≥60 years, a BMI<25, and the presence of a varus knee deformity were independent risk factors for preoperative OP in the postmenopausal women awaiting TKA. CONCLUSION: The prevalence of OP in Chinese postmenopausal women awaiting TKA is higher than that in the age/ethnicity-adjusted normal population. An age ≥60 years, a BMI<25, and the presence of a varus knee deformity are independent risk factors that can be used to predict preoperative OP in this population.

Efficacy of a three-day prolonged-course of multiple-dose versus a single-dose of tranexamic acid in total hip and knee arthroplasty.

BACKGROUND: The application of tranexamic acid (TXA) in total hip arthroplasty (THA) and total knee arthroplasty (TKA) has brought momentous changes in blood management. However, the optimal regimen of TXA has not yet been identified. This study aimed to compare the efficacy of a three-day prolonged-course of multiple-dose of TXA with a single pre-operative dose of TXA in patients who undergo THA and TKA. METHOD: We retrospectively analyzed two groups of consecutive patients who received primary unilateral THA and TKA from 2015 to 2017. One group received a three-day prolonged-course of multiple-dose of TXA, while another group received a single-dose of TXA. The primary outcomes included the changes in hemoglobin (Hb), estimated total blood loss (TBL), and transfusion rate; the secondary outcomes included the platelet (PLT) counts, inflammatory markers, and fibrinolysis parameters. RESULTS: A total of 193 THA and 166 TKA procedures were included for comparison. Compared with the patients who received a single-dose of TXA, the patients who received a three-day prolonged-course of multiple-dose of TXA had smaller post-operative drops in Hb levels, which led to consistently significantly higher Hb levels in both THA and TKA. Therefore, the use of multiple-dose of TXA was associated with significantly lower maximum Hb drops and estimated TBL in both THA (24.58±11.43 vs. 30.38±11.33 g/L, P=0.001; 685.88±412.02 vs. 968.94±479.9 mL, P<0.0001) and TKA (18.04±9.75 vs. 27.24±10.99 g/L, P<0.0001; 497.35±291.03 vs. 816.51±354.38 mL, P<0.0001), and marginally reduced transfusion requirements (THA: 1/65 vs. 10/128; TKA: 0/70 vs. 2/96). The multiple-dose group also showed higher PLT counts, continuously reduced inflammatory responses, and significantly and durably attenuated fibrinolytic responses. CONCLUSIONS: A three-day prolonged-course of multiple-dose of TXA was consistently effective in reducing post-operative Hb drops, estimated TBL, inflammatory responses, and fibrinolytic responses, which could be recommended for clinical practice. However, these findings need to be confirmed by prospective studies.

Application of thrombelastography (TEG) for safety evaluation of tranexamic acid in primary total joint arthroplasty.

BACKGROUND: Questions remain, mainly concerning whether tranexamic acid (TXA) is truly safe since all available trials were underpowered to identify clinically important differences. The objective of this study is to evaluate the safety of TXA by using a novel technique-thromboelastography (TEG). METHODS: A retrospective review was conducted on 359 consecutive patients who underwent primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) and received multiple-dose or single-dose of TXA at a tertiary academic center. TEG parameters, TEG coagulation status, conventional coagulation test parameters, and incidence of thrombotic events were used for safety evaluation. RESULTS: Compared with single-dose cohort, patients who received multiple-dose of TXA had consistent statistically significant shortened R times on post-operative day 1 (POD1) and POD3 in both THA (POD1: 4.06 ± 0.71 s versus 4.45 ± 1.28 s, P = 0.011; POD3: 4.36 ± 0.83 s versus 5.12 ± 1.64 s, P < 0.0001) and TKA (POD1: 3.90 ± 0.73 s versus 4.29 ± 0.92 s, P = 0.011; POD3: 4.24 ± 0.94 s versus 4.65 ± 1.07 s, P = 0.023), while the K, α-angle, and MA values were similar during the perioperative period. TEG coagulation status analysis indicated that patients were significantly (P = 0.003) more likely with hypercoagulable status during the course of multiple-dose TXA. Conventional coagulation test parameters were similar. Only one patient developed calf vein thrombosis in the multiple-dose cohort. CONCLUSIONS: Multiple-dose of TXA was associated with aggravated hypercoagulable state when compared with single-dose of TXA, but this prothrombotic state does not provoke thrombosis when combined with appropriate anticoagulant therapy. Therefore, multiple-dose of TXA remains safe and could be recommended for clinical practice. Potential benefits and possible risks should be trade-off when considering increasing the dosage and frequency of TXA on the present basis. TRIAL REGISTRATION: ChiCTR1800015422 .

Comparison of periprosthetic bone remodeling after implantation of anatomic and tapered cementless femoral stems in total hip arthroplasty: A prospective cohort study protocol.

INTRODUCTION: Current total hip arthroplasty (THA) implant usage trends favor cementless fixation, and plenty studies have demonstrated that numbers of cementless femoral stems are associated with excellent long-term survivorship and functional outcomes. Various types of cementless femoral stems have been developed and utilized in multiple applications, including straight, tapered, anatomic, customized, short, and even neck stems. All of these designs aimed to achieve maximal primary stability and promote osseointegration. Nevertheless, stress-shielding and periprosthetic bone loss continue to occur and remain critical issues in promoting long-term survivorship of THA. Considering anatomic and tapered stems are the most popular cementless designs today, this prospective cohort study aimed to investigate the effect of stem design on stress-shielding and periprosthetic bone remodeling after implantation of an anatomic stem with proximal fixation (Ribbed Hip system; Waldemar Link, Hamburg, Germany) and the direct comparison to a fully coated tapered stem (LCU Hip system; Waldemar Link). MATERIALS AND METHODS: This prospective cohort study will comprise patients who receive primary unilateral THA with the Ribbed anatomic hydroxyapatite (HA)-coated stem or LCU tapered fully HA-coated stem. The changes in periprosthetic bone mineral density after insertion of Ribbed and LCU stem prostheses will be assessed by means of dual-energy X-ray absorptiometry in the periprosthetic region of interest according to Gruen and colleagues. Standard anteroposterior and lateral plain radiography will be performed for qualitative assessment of the periprosthetic bone remodeling. The following items will be analyzed or measured on follow-up radiographs to compare with the initial appearance on the radiographs taken immediately postoperatively: cortical thickness in each Gruen zone, fitness of the distal stem within the isthmus, femoral stem alignment, radiolucent line, reactive line, periosteal bone reactions, and subsidence. Biologic fixation and stability of the cementless implant will be evaluated using Engh grading scale, and heterotopic ossification will be graded according to Brooker classification. Furthermore, Harris hip score and Western Ontario and McMaster Universities Osteoarthritis Index Score will also be assessed for postoperative functional evaluation. These radiologic and clinical assessments will be taken postoperatively, at 6 months, 1, 2, 3, 4, and 5 years after surgery. ETHICS AND DISSEMINATION: This study was approved by The First Affiliated Hospital of Chongqing Medical University Ethics Committee. The study results will be disseminated at national and international conferences and published in peer-reviewed journals. STUDY REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org.cn): ChiCTR1800017841.