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Abstract Background Osteoarthritis (OA) is a degenerative joint disease with an immense unmet medical need. FGF18 protein is a potential regenerative factor for cartilage repair. However, traditional protein delivery methods have limited efficacy due to the short lifetime and shallow infiltration. Results In this work, we discovered that lipid nanoparticle (LNP) can infiltrate and deliver FGF18 mRNA deeper in the cartilage than proteins. After mRNA UTR optimization and chemical modification, the expression of FGF18 can last up to 6 days in the cartilage. Furthermore, delivering FGF18 mRNA activates FOXO3a-autophagy pathway, which protects against chondrocyte degeneration and senescence. Local intra-articular injection of FGF18 mRNA-LNP significantly alleviates OA symptoms in DMM and senile OA models. Sustained expression and accessibility of FGF18-mRNA to deeper chondrocytes makes LNP-mRNA more effective than FGF18 recombinant protein. Conclusions In summary, this study presents a novel approach superior to recombinant protein alone and holds promise as a new therapeutic strategy for OA. Graphical abstract

Purpose: Preoperative planning is critical for total knee arthroplasty (TKA) performed with surgical robots, as it involves establishing a coordinate system to calculate the angle values of the components. This coordinate system serves as a reference during the surgical planning stage. This study aimed to develop a newly custom coordinate system suitable for integration with a surgical robot system. Methods: The “Skywalker” surgical robot system was used to import computed tomography (CT) images of the entire lower extremities from 50 patients diagnosed with osteoarthritis. Three-dimensional reconstruction was subsequently performed. The TKA component was positioned at a fixed angle using the newly developed custom coordinate system. The angle values of the components, based on the standard CT coordinate system, were then recorded without altering their positioning. These values were analyzed to assess the differences between the two coordinate systems. Results: The mean and standard deviation values for the coronal, sagittal, and transverse plane positioning of the femoral component (absolute value of error) were 0.004° ± 0.020°, 0.006° ± 0.024°, and 0.158° ± 0.186°, respectively. Similarly, the mean and standard deviation values for the coronal, sagittal, and transverse plane positioning of the tibial component (absolute value of error) were 0.544° ± 0.452°, 0.042° ± 0.076°, and 0.348° ± 0.445°, respectively. Conclusion: This newly developed custom coordinate system can be employed for preoperative planning in Skywalker surgical robot system-assisted TKA, particularly for patients with significant positional abnormalities in their CT scans.

Background Preoperative evaluation of femoral anteversion to predict postoperative stem anteversion aids the selection of an appropriate prosthesis and optimizes the combined anteversion in total hip arthroplasty (THA) for developmental dysplasia of the hip (DDH). The conventional prediction methods are based on the femoral anteversion measurement at the location of the femoral head and/or neck. However, varied differences between femoral anteversion and postoperative stem anteversion were demonstrated. This study investigated the predictive role of a new method based on the principle of sagittal three‐point fixation. Methods From January 2017 to December 2018, a total of 133 DDH hips that underwent THA were retrospectively analyzed. There were 76 Crowe type I, 27 type II, and 30 type III hips. The single‐wedge stem was used in 49 hips, and the double‐wedge stem was used in 84 hips. Preoperative native femoral anteversion at the femoral head–neck junction, anterior cortex anteversion at 2 levels of the lesser trochanter, posterior cortex anteversion at 5 levels of the femoral neck, and postoperative stem anteversion were measured using two‐dimensional computed tomography. Predictive anteversion by the new method was calculated as the average anteversion formed by the anterior cortex at the lesser trochanter and the posterior cortex at the femoral neck. Results For hips with different neck heights, different Crowe types, different stem types, or different femoral anteversions, native femoral anteversion showed widely varied differences and correlations with stem anteversion, with differences ranging from −1.27 ± 8.33° to −13.67 ± 9.47° and correlations ranging from 0.122 (p = 0.705, no correlation) to 0.813. Predictive anteversion formed by the anterior cortex at the lesser trochanter proximal base and posterior cortex 10 mm above the lesser trochanter proximal base showed no significant difference with stem anteversion, with less varied differences (0.92 ± 7.52°) and good to excellent correlations (r = 0.826). Conclusion Adopting our new method, predictive anteversion, measured as the average anteversion of the anterior cortex at the lesser trochanter proximal base and posterior cortex 10 mm above the lesser trochanter proximal base, predicted postoperative stem anteversion more reliably than native femoral anteversion.

IntroductionThis investigation leverages advanced machine learning (ML) techniques to dissect the complex relationship between heavy metal exposure and its impacts on osteoarthritis (OA) and rheumatoid arthritis (RA). Utilizing a comprehensive dataset from the National Health and Nutrition Examination Survey (NHANES) spanning from 2003 to 2020, this study aims to elucidate the roles specific heavy metals play in the incidence and differentiation of OA and RA.MethodsEmploying a phased ML strategy that encompasses a range of methodologies, including LASSO regression and SHapley Additive exPlanations (SHAP), our analytical framework integrates demographic, laboratory, and questionnaire data. Thirteen distinct ML models were applied across seven methodologies to enhance the predictability and interpretability of clinical outcomes. Each phase of model development was meticulously designed to progressively refine the algorithm’s performance.ResultsThe results reveal significant associations between certain heavy metals and an increased risk of arthritis. The phased ML approach enabled the precise identification of key predictors and their contributions to disease outcomes.DiscussionThese findings offer new insights into potential pathways for early detection, prevention, and management strategies for arthritis associated with environmental exposures. By improving the interpretability of ML models, this research provides a potent tool for clinicians and researchers, facilitating a deeper understanding of the environmental determinants of arthritis.

Abstract Background Nickel-Titanium shape-memory sawtooth-arm embracing clamps (SSECs) have been used in revision total hip arthroplasties (rTHAs) to protect stem stability. This study was to introduce this technique and report its mid to long-term clinical and radiographic outcomes. Methods We retrospectively reviewed all patients implanted with SSECs in our department from January 2008 to December 2015. 41 patients (41 hips) were finally included. Radiographs and Harris hip scores (HHS) were collected. Radiographs were blindly analyzed for evidence of loosening, subsidence and stress shielding. HHS were compared to previous records by student’s t tests. The average follow-up period was 9.3 years. Results All stems were stably fixed with no signs of loosening. The mean stem subsidence was 0.9 mm (range, 0 to 3 mm). Only one patient (2.4%) demonstrated the fourth degree of stress shielding, with the others none or minor bone resorption. The mean HHS at the final follow-up was 84.2 (range, 81 to 91), which was improved from 17.4 (range, 0 to 37) before surgery. No implant failures or re-revisions occurred. Dislocation occurred in 1 case during the follow-up period. Conclusions The SSEC protected stem fixation and achieved favorable clinical and radiographic outcomes in this 9-year follow-up study. It offered an additional extramedullary fixation option for surgeons to choose from in treating complex femoral revision arthroplasties.

Background: Total joint arthroplasty (TJA) is an orthopedic procedure commonly used to treat damaged joints. Despite the efficacy of TJA, postoperative complications, including aseptic prosthesis loosening and infections, are common. Moreover, the effects of individual genetic susceptibility and modifiable risk factors on these complications are unclear. This study analyzed these effects to enhance patient prognosis and postoperative management. Methods: We conducted an extensive genome-wide association study (GWAS) and Mendelian randomization (MR) study using UK Biobank data. The cohort included 2964 patients with mechanical complications post-TJA, 957 with periprosthetic joint infection (PJI), and a control group of 398,708 individuals. Genetic loci associated with postoperative complications were identified by a GWAS analysis, and the causal relationships of 11 modifiable risk factors with complications were assessed using MR. Results: The GWAS analysis identified nine loci associated with post-TJA complications. Two loci near the PPP1R3B and RBM26 genes were significantly linked to mechanical complications and PJI, respectively. The MR analysis demonstrated that body mass index was positively associated with the risk of mechanical complications (odds ratio [OR]: 1.42; p < 0.001). Higher educational attainment was associated with a decreased risk of mechanical complications (OR: 0.55; p < 0.001) and PJI (OR: 0.43; p = 0.001). Type 2 diabetes was suggestively associated with mechanical complications (OR, 1.18, p = 0.02), and hypertension was suggestively associated with PJI (OR, 1.41, p = 0.008). Other lifestyle factors, including smoking and alcohol consumption, were not causally related to postoperative complications. Conclusions: The genetic loci near PPP1R3B and RBM26 influenced the risk of post-TJA mechanical complications and infections, respectively. The effects of genetic and modifiable risk factors, including body mass index and educational attainment, underscore the need to perform personalized preoperative assessments and the postoperative management of surgical patients. These results indicate that integrating genetic screening and lifestyle interventions into patient care can improve the outcomes of TJA and patient quality of life.

Abstract Background Aspirin is a commonly used antipyretic, analgesic, and anti-inflammatory drug. Numerous researches have demonstrated that aspirin exerts multiple biological effects on bone metabolism. However, its spatiotemporal roles remain controversial according to the specific therapeutic doses used for different clinical conditions, and the detailed mechanisms have not been fully elucidated. Hence, in the present study, we aimed to identify the dual effects of different aspirin dosages on osteoclastic activity and osteoblastic bone formation in vitro and in vivo. Methods The effects of varying doses of aspirin on osteoclast and osteoblast differentiation were evaluated in vitro. The underlying molecular mechanisms were detected using quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence techniques. An ovariectomized rat osteoporosis model was used to assess the bone-protective effects of aspirin in vivo. Results Aspirin dose-dependently suppressed RANKL-induced osteoclasts differentiation and bone resorption in vitro and reduced the expression of osteoclastic marker genes, including TRAP, cathepsin K, and CTR. Further molecular analysis revealed that aspirin impaired the RANKL-induced NF-κB and MAPK signaling pathways and prevented the nuclear translocation of the NF-κB p65 subunit. Low-dose aspirin promoted osteogenic differentiation, whereas these effects were attenuated when high-dose aspirin was administered. Both low and high doses of aspirin prevented bone loss in an ovariectomized rat osteoporosis model in vivo. Conclusion Aspirin inhibits RANKL-induced osteoclastogenesis and promotes osteogenesis in a dual regulatory manner, thus preventing bone loss in vivo. These data indicate that aspirin has potential applications in the prevention and treatment of osteopenia.

Objective The oscillating saw has some inherent disadvantages, such as notch formation and blood splash. The objective is to introduce the Gigli saw as a substitute osteotomy tool when oscillating saw malfunctions occur during surgery. Methods During our retrospective study, 120 patients (120 hips) who underwent primary total hip arthroplasty (THA) because of femoral neck fracture, femoral head necrosis, developmental hip dysplasia (Crowe I), or primary osteoarthritis between October 2017 and April 2020 at our institute were included. Sixty patients (26 men and 34 women) with a mean age of 67.3 years (±15.1 years) underwent femoral neck osteotomy using a Gigli saw. The other 60 patients (32 men and 28 women) with a mean age of 64.4 years (±18.8 years) underwent femoral neck osteotomy using an oscillating saw. Intraoperative evaluations, including osteotomy time, osteotomy height, number of notch formations, and blood splash generation, were performed. Routine anteroposterior views of the pelvis and proximal femur were obtained for all patients after surgery. Results The mean osteotomy times were 26.60 ± 14.80 s and 31.80 ± 14.20 s with the oscillating saw and Gigli saw, respectively (t = 1.964, P = 0.0519). The mean osteotomy heights were 1.26 ± 0.22 cm and 1.20 ± 0.14 cm with the oscillating saw and Gigli saw, respectively (t = 1.782, P = 0.0773). The use of a Gigli saw did not result in bone notch formation or blood splash generation when multiple blood splashes were generated in the oscillating saw group. Postoperative radiographs showed no prostheses malposition in the Gigli saw and oscillating saw groups. Conclusion The Gigli saw has various advantages and can be a substitute tool for femoral neck osteotomy during THA when oscillating saw malfunctions occur.

Background: Postoperative complications following total hip arthroplasty (THA) often require revision surgery. X-rays are usually used to detect such complications, but manually identifying the location of the problem and making an accurate assessment can be subjective and time-consuming. Therefore, in this study, we propose a multi-branch network to automatically detect postoperative complications on X-ray images.Methods: We developed a multi-branch network using ResNet as the backbone and two additional branches with a global feature stream and a channel feature stream for extracting features of interest. Additionally, inspired by our domain knowledge, we designed a multi-coefficient class-specific residual attention block to learn the correlations between different complications to improve the performance of the system.Results: Our proposed method achieved state-of-the-art (SOTA) performance in detecting multiple complications, with mean average precision (mAP) and F1 scores of 0.346 and 0.429, respectively. The network also showed excellent performance at identifying aseptic loosening, with recall and precision rates of 0.929 and 0.897, respectively. Ablation experiments were conducted on detecting multiple complications and single complications, as well as internal and external datasets, demonstrating the effectiveness of our proposed modules.Conclusion: Our deep learning method provides an accurate end-to-end solution for detecting postoperative complications following THA.

Abstract Background The COVID-19 pandemic has become a huge threat to human health, infecting millions of people worldwide and causing enormous economic losses. Many novel small molecule drugs have been developed to treat patients with COVID-19, including Paxlovid, which block the synthesis of virus-related proteins and replication of viral RNA, respectively. Despite satisfactory clinical trial results, attention is now being paid to the long-term side effects of these antiviral drugs on the musculoskeletal system. To date, no study has reported the possible side effects, such as osteoarthritis, of Paxlovid. This study explored the effects of antiviral drug, Paxlovid, on chondrocyte proliferation and differentiation. Methods In this study, both in vitro and in vivo studies were performed to determine the effect of Paxlovid on chondrocyte degeneration and senescence. Furthermore, we explored the possible mechanism behind Paxlovid-induced acceleration of cartilage degeneration using transcriptome sequencing and related inhibitors were adopted to verify the downstream pathways behind such phenomenon. Results Paxlovid significantly inhibited chondrocyte extracellular matrix protein secretion. Additionally, Paxlovid significantly induced endoplasmic reticulum stress, oxidative stress, and downstream ferroptosis, thus accelerating the senescence and degeneration of chondrocytes. In vivo experiments showed that intraperitoneal injection of Paxlovid for 1 week exacerbated cartilage abrasion and accelerated the development of osteoarthritis in a mouse model. Conclusions Paxlovid accelerated cartilage degeneration and osteoarthritis development, potentially by inducing endoplasmic reticulum stress and oxidative stress. Long-term follow-up is needed with special attention to the occurrence and development of osteoarthritis in patients treated with Paxlovid.

Abstract Background Accurate assessment of acetabular defects and designing precise and feasible surgical plans are essential for positive outcomes of hip revision arthroplasty. Additive manufacturing (AM) is a novel technique to print physical object models. We propose a three-dimensional acetabular bone defect classification system aided with AM model, and further assess its reliability and validity under blinded conditions. Methods We reviewed 104 consecutive patients who underwent hip revision arthroplasty at our department between January 2014 and December 2019, of whom 45 had AM models and were included in the reliability and validity tests. Three orthopedic surgeons retrospectively evaluated the bone defects of these 45 patients with our proposed classification, made surgical plans, and repeated the process after 2 weeks. The reliability and validity of the classification results and corresponding surgical plans were assessed using the intra-class correlation coefficient or kappa correlation coefficient. Results The reliability and validity of the classification results were excellent. The mean initial intra-class correlation coefficient for inter-observer reliability was 0.947, which increased to 0.972 when tested a second time. The intra-observer reliability ranged from 0.958 to 0.980. Validity of the classification results also showed a high kappa correlation coefficient of 0.951–0.967. When considering corresponding surgical plans, the reliability and validity were also excellent, with intra-class correlation coefficients and kappa correlation coefficients measuring all over 0.9. Conclusions This three-dimensional acetabular defect classification has excellent reliability and validity. Using this classification system and AM models, accurate assessment of bone defect and reliable surgical plans could be achieved. This classification aided with AM is a promising tool for surgeons for preoperative evaluation.

Abstract Background Mechanical failure, power shortage, and inadvertent contamination of the oscillating saw occasionally occurs in actualizing femoral neck osteotomy during total hip arthroplasty (THA); however, no appropriate alternative solution is currently available. This study aimed to introduce a novel osteotomy instrumentation (fretsaw, jig, cable passer hook) as a substitute tool while the oscillating saw was unavailable during THA. Methods This study included 40 patients (40 hips) who underwent femoral neck osteotomy during primary THA using the new osteotomy instrumentation (n = 20) and the oscillating saw (n = 20). Clinical data and intraoperative findings of all patients were evaluated. Results The mean osteotomy time was 22.3 ± 3.1 s (range, 17–30 s) and 29.4 ± 3.7 s (range, 25–39 s) in the oscillating saw group and in the new osteotomy instrumentation group, respectively (P

Abstract Background Lipped or elevated acetabular liners are to improve posterior stability and are widely used in hip arthroplasty. However, concerns of increasing impingement exist when using such liners and optimal orientation of the elevated rim remains unknown. We aimed to identify the impact of lipped liner on the range of motion (ROM) before impingement and propose its optimal orientation. Methods An isochoric three-dimensional model of a general hip-replacement prosthesis was generated, and flex-extension, add-abduction and axial rotation were simulated on a computer. The maximum ROM of the hip was measured before the neck impinged on the liner. Different combinations of acetabular anteversion angles ranging from 5 to 30 degrees, and lipped liner orientations from posterior to anterior were tested. Results When acetabular anteversion was 10 or 15 degrees, placing the lip of the liner in the posterosuperior of the acetabulum allowed satisfactory ROM in all directions. When acetabular anteversion was 20 degrees, extension and external rotation were restricted. Adjusting the lip to the superior restored satisfactory ROM. When acetabular anteversion was 25 degrees, only placing the lip into the anterosuperior could increase extension and external rotation to maintain satisfactory ROM. Conclusions This study showed that optimal lipped liner orientation should depend on acetabular anteversion. When acetabular anteversion was smaller than 20 degrees, placing lip in the posterior allowed an optimally ROM. When acetabular anteversion was greater than 20 degrees, adjusting lip to the anterior allowed a comprehensive larger ROM to avoid early impingement.

BackgroundThis study aimed to explore whether pre- or postoperative hip structures or surgical changes significantly influence hip range of motion (ROM) symmetry in patients with hip dysplasia during gait after total hip arthroplasty (THA) and provide possible surgical suggestions.MethodsFourteen patients with unilateral hip dysplasia underwent computed tomography before and after surgery to create three-dimensional hip models. Pre- and postoperative acetabular and femoral orientations, hip rotation centers (HRC), and femoral lengths were measured. Bilateral hip ROM during level walking after THA was quantified using dual fluoroscopy. The ROM symmetry in flexion-extension, adduction-abduction, and axial rotation was calculated using the symmetry index (SI). The relationship between SI and the above anatomical parameters and demographic characteristics was tested using Pearson's correlation and linear regression.ResultsThe average SI values for flexion-extension, adduction-abduction, and axial rotation during gait were −0.29, −0.30, and −0.10, respectively. Significant correlations were detected mainly in the postoperative HRC position. A distally placed HRC was associated with increased SI values for adduction-abduction (R = −0.47, p = 0.045), while a medially placed HRC was associated with decreased SI values for axial rotation (R = 0.63, p = 0.007). A regression analysis indicated that horizontal HRC positions significantly determined axial rotational symmetry (R2 = 0.40, p = 0.015). Normal axial rotation SI values were achieved with HRC between 17 mm medially and 16 mm laterally.ConclusionsPostoperative HRC position was significantly correlated with gait symmetry in the frontal and transverse planes in patients with unilateral hip dysplasia after THA. Surgical reconstruction of the HRC to between 17 mm medially and 16 mm laterally may contribute to gait symmetry.

Background: Calcium phosphate silicate (Ca5(PO4)2SiO4 or CPS) is a promising bioceramic for bone grafting. Iron (Fe) is a trace element in the human body that has been reported to enhance the mechanical strength of CPS ceramics. However, the exact biofunctions of Fe, combined with another human trace element, viz. silicon (Si), in CPS and the optimal dose for Fe addition must be further investigated. Methods: In vitro: the morphology, structure and cell adhesion were observed by SEM; the ability to promote osteogenic differentiation and mineralization was explored by ALP and alizarin red staining; the expression of osteogenic-specific genes and proteins was detected by PCR, WB and immunofluorescence. In vivo: Further exploration of bone regeneration capacity by establishing a skull defect model. Results: In vitro, we observed increased content of adhesion-related proteins and osteogenic-related genes expression of Fe-CPS compared with CPS, as demonstrated by immunofluorescence and polymerase chain reaction experiments, respectively. In vivo micro-computed tomography images, histomorphology, and undecalcified bone slicing also showed improved osteogenic ability of Fe-CPS bioceramics. Conclusion: With the addition of Fe2O3, the new bone formation rate of the Fe-CPS scaffold after 12 weeks increased from 9.42% to 43.76%. Moreover, both in vitro and in vivo experimental outcomes indicated that Fe addition improved the CPS bioceramics in terms of their osteogenic ability by promoting the expression of osteogenic-related genes. Fe-CPS bioceramics can be employed as a novel material for bone tissue engineering on account of their outstanding new bone formation ability. The translational potential of this article: This study suggests that Fe-CPS bioceramics can be employed as a novel material for bone tissue engineering on account of their outstanding new bone formation ability,which provides promising therapeutic implants and strategies for the treatment of large segmental bone defects.

BackgroundBone defects in revision total hip arthroplasties (rTHAs) caused by osteolysis are routinely treated with autografts or allografts, despite their various disadvantages. Currently, little is known about the prognosis of ungrafted cavities with complete debridement following prosthetic revision in rTHAs with component loosening, as few reports have focused on the application of debridement without bone grafting in osteolytic lesions that do not compromise structural stability in revision THAs with revised components.MethodsIn this study, 48 patients receiving rTHAs with components revised for aseptic loosening with osteolysis between 2015 and 2019 were included. Anteroposterior and lateral radiographs of hips before and after revision surgery and last follow-up were compared to measure whether the size of the debrided osteolytic cavity without bone graft had changed.ResultsIn total, 48 patients with 59 osteolytic lesions were enrolled. The mean follow-up period was 3.33 years (range 2–6 years). None of the 59 cavities had progressed at the last follow-up, and 11 (18.6%) regressed. Two patients underwent re-revision according to dislocation during follow-up.ConclusionIn rTHAs with revised components, osteolytic lesions that do not influence structural stability could be debrided without grafting to avoid the disadvantages of grafting. Debridement and component revision are sufficient to prevent the progression of osteolytic lesions during surgery, without having adverse effects on the short-to mid-term prognosis.

The central physiological role of the bone marrow renders bone marrow stromal cells (BMSCs) particularly sensitive to aging. With bone aging, BMSCs acquire a differentiation potential bias in favor of adipogenesis over osteogenesis, and the underlying molecular mechanisms remain unclear. Herein, we investigated the factors underlying age-related changes in the bone marrow and their roles in BMSCs’ differentiation. Antibody array revealed that CC chemokine ligand 3 (CCL3) accumulation occurred in the serum of naturally aged mice along with bone aging phenotypes, including bone loss, bone marrow adiposity, and imbalanced BMSC differentiation. In vivo Ccl3 deletion could rescue these phenotypes in aged mice. CCL3 improved the adipogenic differentiation potential of BMSCs, with a positive feedback loop between CCL3 and C/EBPα. CCL3 activated C/EBPα expression via STAT3, while C/EBPα activated CCL3 expression through direct promoter binding, facilitated by DNA hypomethylation. Moreover, CCL3 inhibited BMSCs’ osteogenic differentiation potential by blocking β-catenin activity mediated by ERK-activated Dickkopf-related protein 1 upregulation. Blocking CCL3 in vivo via neutralizing antibodies ameliorated trabecular bone loss and bone marrow adiposity in aged mice. This study provides insights regarding age-related bone loss and bone marrow adiposity pathogenesis and lays a foundation for the identification of new targets for senile osteoporosis treatment.

Abstract Purpose This study was aimed to explore (1) location on AP pelvic X-ray that displayed bone stock in anterosuperior acetabulum; (2) whether X-ray could provide enough evidence to evaluate whether bone stock could provide support for acetabular cup; (3) criteria to determine whether anterosuperior bone stock could provide sufficient support for cup on X-ray. Methods Our study retrospectively collected 43 patients who underwent revision THA for cup loosening from 2014 to 2019. The position of anterosuperior acetabular bone stock was compared between X-ray and CT-based 3-D reconstruction. Seventy-millimeter acetabular cup was implanted simulatively to obtain the contact line between acetabular cup and superolateral remaining bone stock. The contact line length and the angle were measured. Patients were divided into cup group and cage group, and ROC curves of both contact line length and angle were drawn. Results The superolateral part of acetabulum on X-ray could reflect the anterosuperior host bone stock of acetabulum according to the comparison of anteroposterior pelvic X-ray and 3-D reconstruction. Critical point was chosen when we got the highest sensitivity with a 100% specificity in ROC curves. The critical values of contact length and angle were 15.58 mm and 25.5°. Conclusions Surgeons could assess the anterosuperior bone stock of acetabulum by AP pelvic X-ray to decide whether revision could be done merely using cup or need customized cage. Clinically, when contact line length was larger than 16 mm or contact angle was larger than 25.5°, adoption of cup could obtain primary stability in the revision surgery in most cases.

Objective: To evaluate accuracy of an innovative “Skywalker” system, a newly designed, robot-assisted operation system for orthopaedics via a clinical trial at knee joint. Methods: We conducted a prospective analysis of the clinical data of 31 patients who underwent total knee arthroplasty assisted by the “Skywalker” robot (Microport, Suzhou, China) from June 2020 to January 2021. Five male patients and 26 female patients aged 69.68 ​± ​6.11 years (range: 57–79 years) were diagnosed with knee osteoarthritis and indicated for surgery. The “Skywalker” surgical robotic system was adopted to make a preoperative plan for knee arthroplasty. When the robotic arm reached the specified position during the operation, a single surgeon performed the osteotomy with a cutting saw through the cutting jig, and the difference between the actual and the expected resection thickness, and the preoperative and postoperative lower limb alignments were measured. Results: The actual error of the resection thickness was the difference between the actual and the expected resection thickness. The absolute error of the resection thickness was the absolute value of the actual error of resection thickness. The absolute errors of the resection thickness of the medial and lateral condyle of the distal femur, the medial and lateral posterior condyle of the femur, and the medial and lateral sides of the tibial plateau were 0.87 ​± ​0.63 ​mm, 1.02 ​± ​0.67 ​mm, 0.74 ​± ​0.46 ​mm, 0.98 ​± ​0.81 ​mm, 0.92 ​± ​0.66 ​mm, and 1.04 ​± ​0.84 ​mm, respectively. The absolute angle errors between the actual postoperative angles and the preoperative planned angles of the lower limb alignment angles, coronal femoral component angles, and coronal tibial component angles were 1.46° ​± ​0.95°, 1.13° ​± ​1.01°, and 1.05° ​± ​0.73°, respectively. Besides, 100% of the absolute error of the HKA angles was within 3°. In addition, compared to the preoperative lower limb alignment angle, 90.32% of the postoperative lower limb alignment angles of 31 patients were closer to 180° after the operation. All 31 patients underwent a successful surgery, and no relevant complications occurred after the operation, such as surgical site infection, deep venous thrombosis, or vascular and nerve injury. Conclusion: The “Skywalker” system has good osteotomy accuracy, can achieve the planned angles well, and is expected to assist surgeons in performing accurate bone cuts and reconstructing planned lower limb alignments in the relevant clinical applications in future.

Abstract Background Atherosclerosis (AS) is a complex disease caused in part by dyslipidemia and chronic inflammation. AS is associated with serious cardiovascular disease and remains the leading cause of mortality worldwide. Mesenchymal stem cells (MSCs) have evolved as an attractive therapeutic agent in various diseases including AS. Human umbilical cord MSCs (UCSCs) have been used in cell therapy trials due to their ability to differentiate and proliferate. The present study aimed to investigate the effect of UCSCs treatment on atherosclerotic plaque formation and the progression of lesions in a high-fat diet rabbit model. Methods Rabbits were fed a high-fat diet and then randomly divided into three groups: control, model, and treatment groups. Rabbits in the treatment group were injected with UCSCs (6 × 106 in 500 μL phosphate buffered saline) after 1 month of high-fat diet, once every 2 weeks, for 3 months. The model group was given PBS only. We analyzed serum biomarkers, used ultrasound and histopathology to detect arterial plaques and laser Doppler imaging to measure peripheral blood vessel blood filling, and analyzed the intestinal flora and metabolism. Results Histological analysis showed that the aortic plaque area was significantly reduced in the treatment group. We also found a significant decrease in macrophage accumulation and apoptosis, an increase in expression of scavenger receptors CD36 and SRA1, a decrease in uptake of modified low–density protein (ox-LDL), and a decrease in levels of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α following UCSCs treatment. We also found that anti-inflammatory cytokines IL-10 and transforming growth factor (TGF)-β expression increased in the aorta atherosclerotic plaque of the treatment group. UCSCs treatment improved the early peripheral blood filling, reduced the serum lipid level, and inhibited inflammation progression by regulating the intestinal flora dysbiosis caused by the high-fat diet. More specifically, levels of the microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) were down-regulated in the treatment group. Conclusions UCSCs treatment alleviated atherosclerotic plaque burden by reducing inflammation, regulating the intestinal flora and TMAO levels, and repairing the damaged endothelium.

Atherosclerosis (AS) is a chronic inflammatory disease of arteries fueled by lipids. It is a major cause of cardiovascular morbidity and mortality. Mesenchymal stem cells have been used for the treatment of atherosclerotic lesions. Adipose-derived stem cells (ADSCs) have been shown to regulate the activation state of macrophages and exhibit anti-inflammatory capabilities. However, the effect of allogeneic ADSCs in the treatment of AS have not been investigated. In this study, the early treatment effect and preliminary mechanism analysis of allogeneic rabbit ADSCs intravenous transplantation were investigated in a high-fat diet rabbit model. The polarization mechanism of rabbit ADSCs on the macrophage was further analyzed in vitro. Compared with the model group, blood lipid levels declined, the plaque area, oxidized low-density lipoprotein (ox-LDL) uptake, scavenger receptor A1 and cluster of differentiation (CD) 36 levels were all significantly reduced, and the accumulation of inflammatory M1 macrophages, apoptosis, interleukin (IL)-6 and tumor necrosis factor (TNF)-α expression were decreased. The endothelial cells (CD31), M2 macrophages, IL-10 and the transforming growth factor (TGF)-β levels increased. In vitro, ADSCs can promote the M1 macrophage phenotypic switch toward the M2 macrophage through their secreted exosomes, and the main mechanism includes increasing arginase 1 expression and IL-10 secretion, declining inducible nitric oxide synthase (iNOS) expression and TNF-α secretion, and activating the STAT6 pathway. Therefore, allogeneic rabbit ADSC transplantation can transmigrate to the aortic atherosclerotic plaques and show a good effect in lowering blood lipids and alleviating atherosclerotic plaque in the early stage of AS by inhibiting ox-LDL uptake, inflammatory response, and endothelial damage.

Critical-sized bone defects are an intractable orthopedic disease which often fails to regenerate spontaneously and requires additional intervention. Current therapies, including autografts and allografts, are not always satisfactory. Herein, the novel calcium phosphate bioceramic-containing silicon (CPS) with a carnotite structure was synthesized. In the present study, CPS was prepared for investigating the biocompatibility and bioactivity in vitro and in vivo in comparison to hydroxyapatite (HA). Our results showed that CPS bioceramics had favorable biocompatibility and rBMSCs could adhere on the surface well in vitro. Moreover, CPS could promote osteogenic differentiation of rBMSCs and the expression of osteogenic differentiation marker genes, including ALP, Runx-2, BSP, OCN, and OPN. In vivo, the results of micro-CT, histomorphometry, and histology analyses showed that CPS significantly enhanced critical-sized calvarial defects healing compared with HA. Overall, the present study demonstrated that CPS bioceramics had satisfactory bioactivities and osteogenic capacities, which could be a potential option for reconstructing critical-sized bone defects.

Aims: In revision total hip arthroplasty (THA), large acetabular bone defects pose challenges for surgeons. Recently, wide application of trabecular tantalum, which has outstanding biocompatibility and mechanical properties, and the development of three-dimensional (3D) printing have led to the introduction of new schemes for acetabular reconstruction. However, few studies have focused on the treatment of bone defects with customized 3D-printed titanium augments combined with tantalum trabecular cup. Thus, we aimed to evaluate the effect of this therapy in patients who underwent revision THAs.Patients and Methods: We included 23 patients with Paprosky type III acetabular bone defects who underwent revision THA between January 2013 and June 2019. The preoperative hip rotation center and functional score were compared with those at 2–7 years (average 4.7 years) postoperatively to evaluate the midterm prognosis of our treatment choice.Results: Postoperatively, the rotation centres of all hips were comparable with those of the contralateral hips. Hip function improved with average Harris Hip Score improved from 33.5 (22.7–40.2) to 86.1 (73.5–95.6) and average Oxford Hip Score improved from 8.3 (0–14) to 38.8 (35–48) during follow-up. One dislocation, which occurred due to extreme hip flexion within 6 weeks, was treated with closed reduction, and no recurrent dislocation occurred. No nerve injury, infection, aseptic loosening, or osteolysis were observed and no re-revision was performed in any patient.Conclusion: Satisfactory midterm outcomes were obtained with 3D-printed titanium augment combined with tantalum cup for the treatment of acetabular defects in revision THA. Changes in the Harris Hip Score and Oxford Hip Score suggested a significant improvement in hip function.

Bone integration on the surface of titanium prosthesis is critical to the success of implant surgery. Good Bone integration at the contact interface is the basis of long-term stability. TiO2 nanotubes have become one of the most commonly used modification techniques for artificial joint prostheses and bone defect implants due to their good biocompatibility, mechanical properties and chemical stability. TiO2 nanotubes can promote F-actin polymerization in bone mesenchymal stem cells (BMSCs) and osteogenic differentiation. The possibility of F-actin as an upstream part to regulate GCN5 initiation of osteogenesis was discussed. The results of gene loss and functional acquisition assay, immunoblotting assay and fluorescence staining assay showed that TiO2 nanotubes could promote the differentiation of BMSCs into osteoblasts. The intervention of TiO2 nanotubes can make BMSCs form stronger F-actin fibre bundles, which can drive the differentiation process of osteogenesis. Our results showed that F-actin mediated nanotube-induced cell differentiation through promoting the expression of GCN5 and enhancing the function of GCN5 and GCN5 was a key regulator of the osteogenic differentiation of BMSCs induced by TiO2 nanotubes as a downstream mediated osteogenesis of F-actin, providing a novel insight into the study of osteogenic differentiation on surface of TiO2 nanotubes.

Abstract Background The purpose of this study was to investigate the association between the severity of Developmental dysplasia of the hip (DDH) and the abnormality in pelvic incidence (PI). Methods This was a retrospective study analyzing 53 DDH patients and 53 non-DDH age-matched controls. Computed tomography images were used to construct three-dimensional pelvic model. The Crowe classification was used to classify the severity of DDH. The midpoint of the femoral head centers and sacral endplates were projected to the sagittal plane of the pelvis. The PI was defined as the angle between a line perpendicular to the sacral plate at its midpoint and a line connecting this point to the axis of the femoral heads. Independent sample t-tests were used to compare the differences between the PI of DDH group and the non-DDH controls group. Kendall’s coefficient of concordance was used to determine the correlation between the severity of DDH and PI. Results Patients with DDH had a significantly (p = 0.041) higher PI than the non-DDH controls (DDH 47.6 ± 8.2°, normal 44.2 ± 8.8°). Crowe type I patients had a significantly (p = 0.038) higher PI (48.2 ± 7.6°) than the non-DDH controls. No significant difference between the PI in Crowe type II or III patients and the PI in non-DDH controls were found (Crowe type II, 50.2 ± 9.6°, p = 0.073; Crowe type III, 43.8 ± 7.2°, p = 0.930). No correlation was found between the severity of DDH and the PI (r = 0.091, p = 0.222). Conclusions No correlation was found between the severity of DDH and the PI. The study confirmed that the PI in DDH (Crowe type I) group was higher than that of the non-DDH control group, while the PI does not correlate with the severity of DDH.

Abstract Titanium and titanium alloys are widely used in orthopedic implants. Modifying the nanotopography provides a new strategy to improve osseointegration of titanium substrates. Filamentous actin (F-actin) polymerization, as a mechanical loading structure, is generally considered to be involved in cell migration, endocytosis, cell division, and cell shape maintenance. Whether F-actin is involved and how it functions in nanotube-induced osteogenic differentiation of mesenchymal stem cells (MSCs) remain to be elucidated. In this study, we fabricated TiO2 nanotubes on the surface of a titanium substrate by anodic oxidation and characterized their features by scanning electron microscopy (SEM), X-ray energy dispersive analysis (EDS), and atomic force microscopy (AFM). Alkaline phosphatase (ALP) staining, Western blotting, qRT-PCR, and immunofluorescence staining were performed to explore the osteogenic potential, the level of F-actin, and the expression of MKL1 and YAP/TAZ. Our results showed that the inner diameter and roughness of TiO2 nanotubes increased with the increase of the anodic oxidation voltage from 30 to 70 V, while their height was 2 μm consistently. Further, the larger the tube diameter, the stronger the ability of TiO2 nanotubes to promote osteogenic differentiation of MSCs. Inhibiting F-actin polymerization by Cyto D inhibited osteogenic differentiation of MSCs as well as the expression of proteins contained in focal adhesion complexes such as vinculin (VCL) and focal adhesion kinase (FAK). In contrast, after Jasp treatment, polymerization of F-actin enhanced the expression of RhoA and transcription factors YAP/TAZ. Based on these data, we concluded that TiO2 nanotubes facilitated the osteogenic differentiation of MSCs, and this ability was enhanced with the increasing diameter of the nanotubes within a certain range (30–70 V). F-actin mediated this process through MKL1 and YAP/TAZ.

Abstract Background Precise evaluation of the hip abductor and adductor muscles function in total hip arthroplasty (THA) patients during gait could help prevent postoperative complications and optimize the rehabilitation training program. The purpose of this study was to elucidate the effects of THA on the hip abductor and adductor muscle lengths and moment arms of in vivo patients during gait. Methods Ten unilateral THA patients received CT scans and dual fluoroscopic imaging for the hip kinematics during gait. The hip abductor and adductor muscle insertions were digitized on the 3D hip model for the determination of their dynamic lines of action and moment arms. Changes in the hip abductor and adductor muscle lengths and moment arms of THA patients between the implanted and non-implanted sides were quantified during gait. Results The adductor longus, adductor brevis, and pectineus of the implanted hips had significantly (P < 0.05) less elongation than that of the non-implanted side during the stance phase. The gluteus medius, gluteus minimus, and piriformis moment arms of the implanted side were significantly shorter. The piriformis muscle moment arm was significantly larger. In the double support phase, the adductor magnus and adductor longus moment arms of the implanted sides were significantly decreased. Conclusions Results suggested that the adverse effects of THA on hip stability. Development of a rehabilitation program considering the effects of THA is essential. Accurate surgical techniques may reduce the impact of THA on the peripheral muscles.

Objective This study aimed to investigate the optimal level of femoral neck for measuring femoral anteversion to predict postoperative stem anteversion in Crowe type I developmental dysplasia of the hip. Methods This retrospective study analyzed 108 Crowe type I hips that underwent THA between January 2016 and December 2017, including 70 women and 19 men with a mean age of 63.08 ± 9.13 (range, 41–83) years. The single‐wedge stem was used in 37 hips, the double‐wedge stem was used in 71 hips. Computed tomography scans were performed pre‐ and post‐operation. Femoral anteversion at six levels of the proximal femur were measured via preoperative two‐dimensional computed tomography. Femoral anteversion at the level of the femoral neck osteotomy plane and postoperative stem anteversion were measured via three‐dimensional reconstructed models. Results The mean follow‐up period was 18.5 months (range, 12–27). The mean preoperative Harris Hip Score was 51.5 ± 8.7 and improved to 90.4 ± 7.8 (P

Surface modification of titanium has been a hot topic to promote bone integration between implants and bone tissue. Titanium dioxide nanotubes fabricated on the surface of titanium by anodic oxidation have been a mature scheme that has shown to promote osteogenesis in vitro. However, mechanisms behind such a phenomenon remain elusive. In this study, we verified the enhanced osteogenesis of BMSCs on nanotopographic titanium in vitro and proved its effect in vivo by constructing a bone defect model in rats. In addition, the role of the mechanosensitive molecule Yap is studied in this research by the application of the Yap inhibitor verteporfin and knockdown/overexpression of Yap in MC3T3-E1 cells. Piezo1 is a mechanosensitive ion channel discovered in recent years and found to be elemental in bone metabolism. In our study, we preliminarily figured out the regulatory relationship between Yap and Piezo1 and proved Piezo1 as a downstream effector of Yap and nanotube-stimulated osteogenesis. In conclusion, this research proved that nanotopography promoted osteogenesis by increasing nuclear localization of Yap and activating the expression of Piezo1 downstream.

Background: Total hip arthroplasty (THA) for hip dysplasia patients is sometimes complex and compromises pathomorphological changes in these patients. However, it remains unclear whether it is preoperative deformities or postoperative structures or anatomic changes during THA that have the most remarkable correlation with the hip dynamic function during gait. The purpose of this study was to investigate this relationship and propose insights into the surgical reconstruction strategy in patients with developmental dysplasia of the hip.Methods: A total of 21 unilateral hip dysplasia patients received computed tomography scans for the creation of 3D hip models before surgery and at the last follow-up. Acetabular and femoral orientations, hip center positions, and femoral length were measured before and after THA. Hip kinematics of the operated side during gait was quantified using a dual fluoroscopic imaging technique. Pearson correlation and multiple linear regression were performed to evaluate the relationship between hip maximum range of motion in six directions and demographics characters and above hip anatomic parameters before and after THA and their changes in surgery.Results: Pearson correlation analysis found significant correlations with the gait range of motion mainly in postoperative structures, including postoperative hip center positions and acetabulum and combined anteversion. Further multiple linear regression indicated that a laterally placed hip center was significantly correlated with an increased internal rotation (R2 = 0.25, p = 0.021), which together with increased postoperative acetabulum anteversion explained 45% of external rotation decreasing (p = 0.004). A proximally placed hip center was correlated with more extension (R2 = 0.30, p = 0.010). No significant demographic characters or preoperative deformities or surgical changes were included into other multiple regression models.Conclusion: Strong correlations between postoperative structures, especially hip center positions and gait range of motion in unilateral hip dysplasia patients after THA were found. It indicated that postoperative prosthesis structures, particularly hip center positions had significant impact on the hip gait motion range and should be treated with particular caution in surgery.

Bone marrow mesenchymal stem cells (BMSCs) play a critical role in bone formation and are extremely sensitive to external mechanical stimuli. Mechanical signals can regulate the biological behavior of cells on the surface of titanium-related prostheses and inducing osteogenic differentiation of BMSCs, which provides the integration of host bone and prosthesis benefits. But the mechanism is still unclear. In this study, BMSCs planted on the surface of TiO2 nanotubes were subjected to cyclic mechanical stress, and the related mechanisms were explored. The results of alkaline phosphatase staining, real-time PCR, and Western blot showed that cyclic mechanical stress can regulate the expression level of osteogenic differentiation markers in BMSCs on the surface of TiO2 nanotubes through Wnt/β-catenin. As an important member of the histone acetyltransferase family, GCN5 exerted regulatory effects on receiving mechanical signals. The results of the ChIP assay indicated that GCN5 could activate the Wnt promoter region. Hence, we concluded that the osteogenic differentiation ability of BMSCs on the surface of TiO2 nanotubes was enhanced under the stimulation of cyclic mechanical stress, and GCN5 mediated this process through Wnt/β-catenin.

ObjectiveFemoral offset (FO) restoration is significantly correlated with functional recovery following total hip arthroplasty (THA). Accurately assessing the effects of FO changes on hip muscles following THA would help improve function and optimize functional outcomes. The present study aimed to (1) identify the impact of FO side difference on the hip muscle moment arms following unilateral THA during gait and (2) propose the optimal FO for a physiological hip muscle function.MethodsIn vivo hip kinematics from eighteen unilateral THA patients during gait were measured with a dual-fluoroscopic imaging system. The moment arms of thirteen hip muscles were calculated using CT-based 3D musculoskeletal models with the hip muscles’ lines of actions. The correlation coefficient (R) between FO and hip muscle moment arm changes compared with the non-implanted hip was calculated. We considered that the FO reconstruction was satisfactory when the abductor moment arms increased, while the extensor, adductor, and flexor moment arms decreased less than 5%.ResultsA decreased FO following THA was significantly correlated with a decrease of the abductor and external rotator moment arms during the whole gait (R > 0.5) and a decrease of extensor moment arms during the stance phase (R > 0.4). An increased FO following THA was significantly associated with shorter flexor moment arms throughout the gait (R < −0.5) and shorter adductor moment arms in the stance phase (R < −0.4). An increase in FO of 2.3–2.9 mm resulted in increased abductor moment arms while maintaining the maximum decrease of the hip muscles at less than 5.0%.ConclusionAn increase of 2–3 mm in FO could improve the abductor and external rotator function following a THA. Accurate surgical planning with optimal FO reconstruction is essential to restoring normal hip muscle function in THA patients.

Background. KDM6A (Lysine (K)-Specific Demethylase 6A) is the driver gene related to esophageal squamous cell carcinoma (ESCC). In order to provide more biological insights into KDM6A, in this paper, we treat PPI (protein-protein interaction) network derived from KDM6A as a conceptual framework and follow it to review its biological function. Method. We constructed a PPI network with Cytoscape software and performed clustering of network with Clust&See. Then, we evaluate the pathways, which are statistically involved in the network derived from KDM6A. Lastly, gene ontology analysis of clusters of genes in the network was conducted. Result. The network includes three clusters that consist of 74 nodes connected via 453 edges. Fifty-five pathways are statistically involved in the network and most of them are functionally related to the processes of cell cycle, gene expression, and carcinogenesis. The biology themes of clusters 1, 2, and 3 are chromatin modification, regulation of gene expression by transcription factor complex, and control of cell cycle, respectively. Conclusion. The PPI network presents a panoramic view which can facilitate for us to understand the function role of KDM6A. It is a helpful way by network approach to perform system review on a certain gene.

PurposeThe purpose of this hospital-based case-control study was to evaluate the patient-related risk factors for aseptic loosening after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in Chinese patients.MethodsFrom January 2000 to December 2012, 67 patients undergoing THA and TKA who developed aseptic loosening were detected as case subjects and 336 patients without aseptic loosening, matched by the year of index surgery and type of surgery, were selected as controls. Conditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThe demographic factors and comorbid conditions associated with a risk-adjusted increase in aseptic loosening (in decreasing order of significance) were a rural place of residence (OR = 2.28; 95% CI: 1.21-4.30; p = 0.011), body mass index (BMI) ≥ 28 kg/m(2) (vs. 18.5-28 kg/m(2)) (OR = 2.29; 95% CI: 1.19-4.41; p = 0.013), developmental dysplasia of the hip (DDH) (OR = 2.91; 95% CI: 1.11-7.66; p = 0.030), tobacco abuse (OR = 2.88; 95% CI: 1.05-7.89; p = 0.039), and age ConclusionsPatients aged

BACKGROUND: The accuracy of synovial fluid (SF) white cell count (WCC) and polymorphonuclear (PMN) cell evaluation for predicting prosthetic joint infection (PJI) at the total hip arthroplasty (THA) or total knee arthroplasty (TKA) site is unknown. Therefore, we performed a meta-analysis to summarize the diagnostic validity of SF-WCC and SF-PMN for diagnosing PJI. METHODS: The MEDLINE, EMBASE, and OVID databases were searched for studies that had evaluated the diagnostic validity of SF-WCC and SF-PMN between January 1990 and May 2013. Meta-analysis methods were used to pool sensitivity, specificity, diagnostic odd ratios (DORs), the area under the receiver-operating characteristic curve (AUC), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and post-test probability. We also conducted heterogeneity, publication bias, subgroup, and meta-regression analyses. RESULTS: Fifteen articles (15 SF-WCC and 14 SF-PMN) that included a total of 2787 patients fulfilled the inclusion criteria and were considered for analysis. The pooled sensitivity and specificity for PJI detection was 0.88 (95% confidence intervals [CI], 0.81-0.93) and 0.93 (95% CI, 0.88-0.96) for SF-WCC and 0.90 (95% CI, 0.84-0.93) and 0.88 (95% CI, 0.83-0.92) for SF-PMN, respectively. The AUC was 0.96 for SF-WCC and 0.95 for SF-PMN. PLR and NLR were 13.3 and 0.13 for SF-WCC, and 7.6 and 0.12 for SF-PMN, respectively. There was no evidence of publication bias. Low-clinical-scenario (pre-test probability, 20%) post-test probabilities were 3% for both negative SF-WCC and SF-PMN results. The subgroup analyses indicated that the sensitivity/specificity of THA were 0.73/0.96 for SF-WCC and 0.85/0.83 for SF-PMN, whereas those of TKA were 0.90/0.91 for SF-WCC and 0.90/0.88 for SF-PMN. We also found that collection of SF-WCC preoperatively had a higher sensitivity than that obtained intraoperatively (0.91 vs. 0.77). CONCLUSIONS: SF-WCC and SF-PMN have an adequate and clinically acceptable diagnostic value for detecting PJI, particularly after TKA.

PURPOSE: The purpose of this hospital-based case-control study was to evaluate the risk factors for periprosthetic joint infection (PJI) of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in Chinese patients. METHOD: From January 2000 to December 2012, 45 patients undergoing THA and TKA who developed PJI were recruited for case subjects; controls were 252 without PJI, matched by year of index for surgery and type of surgery. Conditional logistic regressions were run to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Demographic factors and comorbid conditions associated with an increased adjusted risk of PJI (in decreasing order of significance) were diabetes (OR = 5.47, 95% CI: 1.77-16.97; p = 0.003), age (65-75 vs. 45-65 years) (OR = 3.36, 95% CI: 1.30-8.69; p = 0.013), BMI (≥28 vs. 18.5-28 kg/m2) (OR = 2.77, 95% CI: 1.20-6.40; p = 0.017), place of residence (rural) (OR = 2.63, 95% CI: 1.13-6.10; p = 0.025) and alcohol abuse (OR = 2.95, 95% CI: 1.06-8.23; p = 0.039). CONCLUSION: Patients with diabetes, older age, BMI of ≥28 kg/m2 and alcohol abuse or living in rural areas, had increased PJI risk. Additional systematic large-scale studies are needed to verify these results.

Intraoperative frozen section (FS) is an effective diagnostic test for periprosthetic joint infection (PJI). We evaluated the diagnostic characteristics of single- and multiplex-site intraoperative FS, and evaluated the results of single-site FS combined with those of C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) for assessing PJI.We studied 156 painful joint arthroplasties in 152 consecutive patients presenting for revision total joint arthroplasty due to PJI. Receiver operating characteristic analysis was used to determine the optimal cutoff values for CRP level, ESR, and intraoperative FS histopathology. Sensitivity, specificity, positive and negative predictive values, and accuracy of the diagnostic tests were assessed using a 2×2 table.We investigated the diagnostic utility of polymorphonuclear leukocyte number (PMN) per high-power field (HPF) on FS. Our data showed that 5 PMNs per HPF is a suitable diagnostic threshold, with a high accuracy in single- and multiplex-site FS. Five PMNs in any 1 of 5 sites had the highest sensitivity of 0.86 and a specificity of 0.96. Five PMNs in every 1 of 5 sites had greater diagnostic utility, with a specificity of 1; however, the sensitivity of this measure fell to 0.62. Five PMNs in single-site FS had a sensitivity of 0.70 and a specificity of 0.94. Five PMNs in single-site FS or CRP level ≥15 mg/L increased the sensitivity to 0.92; however, the specificity decreased to 0.79.Compared with single-site FS, any 1 positive site on multiplex-site FS may improve sensitivity, while every 1 positive site on multiplex-site FS may improve specificity. Five PMNs in any 1 of 5 sites on FS has excellent utility for the diagnosis of PJI. Additional systematic large-scale studies are needed to verify this result.

BACKGROUND: Prospective studies that have examined the association between dietary magnesium intake and serum magnesium concentrations and the risk of cardiovascular disease (CVD) events have reported conflicting findings. We undertook a meta-analysis to evaluate the association between dietary magnesium intake and serum magnesium concentrations and the risk of total CVD events. METHODOLOGY/PRINCIPAL FINDINGS: We performed systematic searches on MEDLINE, EMBASE, and OVID up to February 1, 2012 without limits. Categorical, linear, and nonlinear, dose-response, heterogeneity, publication bias, subgroup, and meta-regression analysis were performed. The analysis included 532,979 participants from 19 studies (11 studies on dietary magnesium intake, 6 studies on serum magnesium concentrations, and 2 studies on both) with 19,926 CVD events. The pooled relative risks of total CVD events for the highest vs. lowest category of dietary magnesium intake and serum magnesium concentrations were 0.85 (95% confidence interval 0.78 to 0.92) and 0.77 (0.66 to 0.87), respectively. In linear dose-response analysis, only serum magnesium concentrations ranging from 1.44 to 1.8 mEq/L were significantly associated with total CVD events risk (0.91, 0.85 to 0.97) per 0.1 mEq/L (P(nonlinearity)= 0.465). However, significant inverse associations emerged in nonlinear models for dietary magnesium intake (P(nonlinearity)= 0.024). The greatest risk reduction occurred when intake increased from 150 to 400 mg/d. There was no evidence of publication bias. CONCLUSIONS/SIGNIFICANCE: There is a statistically significant nonlinear inverse association between dietary magnesium intake and total CVD events risk. Serum magnesium concentrations are linearly and inversely associated with the risk of total CVD events.

The central nervous system has the capacity to activate profound neuroprotection following sub-lethal stress in a process termed preconditioning. To gain insight into this potent survival response we developed a functional cloning strategy that identified 31 putative neuroprotective genes of which 28 were confirmed to provide protection against oxygen-glucose deprivation (OGD) or excitotoxic exposure to N-methyl-D-aspartate (NMDA) in primary rat cortical neurons. These results reveal that the brain possesses a wide and diverse repertoire of neuroprotective genes. Further characterization of these and other protective signals could provide new treatment opportunities for neurological injury from ischemia or neurodegenerative disease.