Standardized 3D-printed trabecular titanium augment and cup for acetabular bone defects in revision hip arthroplasty: a mid-term follow-up study.

BACKGROUND: The aim of this study was to assess the feasibility and outcomes of standardized three-dimensional (3D)-printed trabecular titanium (TT) cups and augments to reconstruct most acetabular defects. METHODS: We included 58 patients with Paprosky type II and III acetabular bone defects who underwent revision hip arthroplasty between 2015 and 2018. Patients who were revised without 3D-printed augments, and cases who were lost to follow-up and died during follow-up were excluded. Radiographic and clinical outcomes were evaluated. A Kaplan-Meier survivorship curve was generated. The mean follow-up was 64.5 (range 49-84) months. RESULTS: In total, 48 (82.8%) acetabular revisions were performed using standardized 3D-printed TT cups and augments, and a retrospective review was conducted on 43 revisions. The average position of the vertical center of rotation and leg length discrepancy were significantly decreased from 42.4 ± 9.1 mm and 38.4 ± 10.7 mm to 22.8 ± 3.4 mm and 4.1 ± 3.0 mm, respectively. Non-progressive radiolucent lines were observed in 3 (7.5%) acetabular components with no indications for revision. The mean Harris hip score, Oxford hip score and EuroQol five-dimensional questionnaire score increased from 33.0 ± 10.7, 11.4 ± 3.4 and 0.29 ± 0.09 to 80.3 ± 8.8, 35.8 ± 2.4 and 0.71 ± 0.10, respectively. The revision-free survival rate of the acetabular component was 93.0% (40/43), with a rate of revision for aseptic loosening of 2.3% (1/43). CONCLUSION: Standardized 3D­printed TT augments and cups could be used to reconstruct the majority of Paprosky type II and III acetabular defects in revision hip arthroplasty and demonstrated encouraging results at mid-term follow-up.

Treatment of periprosthetic knee infection and coexistent periprosthetic fracture: A case report and literature review.

BACKGROUND: Periprosthetic joint infection (PJI) and periprosthetic fracture (PPF) are among the most serious complications following total knee arthroplasty. Herein, we present one patient with these two complications with details on the characteristics, treatment strategy, and outcome. CASE SUMMARY: A 69-year-old female patient who suffered from PJI and PPF following total knee arthroplasty was treated by a two-stage revision surgery. After thorough foreign material removal and debridement, we used a plate that was covered with antibiotic-loaded bone cement to link with a hand-made cement spacer to occupy the joint space and fix the fracture. Although the infection was cured, the fracture did not heal and caused bone defect due to the long interval between debridement and revision. In the revision surgery, a cemented stem and cortical allogenic splints were used to reconstruct the fracture and bone defect. At the final follow-up 27 mo after revision, the patient was satisfied with postoperative knee functions with satisfactory range of motion (104º) and Hospital for Special Surgery knee score (82 points). The radiographs showed no loosening of the prosthesis and that the bone grafts healed well with the femur. CONCLUSION: Our two-stage revision surgery has proved to be successful and may be considered in other patients with PJI and PPF.

Direct detection and identification of periprosthetic joint infection pathogens by metagenomic next-generation sequencing.

This study assessed the application of metagenomic next-generation sequencing in pathogen detection of periprosthetic joint infections. A total of 95 cases who previously had undergone hip and knee replacement undergoing revision from January 2018 to January 2021 were included in this study. Specimens of synovial fluid and deep-tissue were collected for culture and metagenomic next-generation sequencing, and patients were retrospectively categorized as infected or aseptic using the Musculoskeletal Infection Society criteria after revision surgery. The sensitivity, specificity, positive and negative predictive values were compared. A total of 36 cases had positive culture results and 59 cases had positive metagenomic next-generation sequencing results. Culture was positive in 34 infected cases (58.6%) and 2 aseptic cases (5.4%). Metagenomic next-generation sequencing was positive in 55 infected cases (94.8%) and 4 aseptic cases (10.8%). Five cases diagnosed with infection had other potential pathogens detected by metagenomic next-generation sequencing. Among the 24 culture-negative periprosthetic joint infections, metagenomic next-generation sequencing was able to identify potential pathogens in 21 cases (87.5%). From sampling to reporting, the average time needed for culture was 5.2 (95% CI 3.1-7.3) days, while that for metagenomic next-generation sequencing was 1.3 (95% CI 0.9-1.7) days. Metagenomic next-generation sequencing is more advantageous in pathogen detection of periprosthetic joint infection after total joint replacement, especially in patients with multiple infections or negative culture results.

Will previous antimicrobial therapy reduce the positivity rate of metagenomic next-generation sequencing in periprosthetic joint infections? A clinical study.

Background: Metagenomic next-generation sequencing (mNGS) is a culture-independent massively parallel DNA sequencing technology and it has been widely used for rapid etiological diagnosis with significantly high positivity rate. Currently, clinical studies on evaluating the influence of previous antimicrobial therapy on positivity rate of mNGS in PJIs are rarely reported. The present study aimed to investigate whether the positivity rate of mNGS is susceptible to previous antimicrobial therapy. Methods: We performed a prospective trial among patients who undergone hip or knee surgery due to periprosthetic joint infection (PJI) to compare the positivity rate of culture and mNGS between cases with and without previous antimicrobial therapy, and the positivity rates between cases with different antimicrobial-free intervals were also analysed. Results: Among 131 included PJIs, 91 (69.5%) had positive cultures and 115 (87.8%) had positive mNGS results. There was no significant difference in the positivity rate of deep-tissue culture and synovial fluid mNGS between cases with and without previous antimicrobial therapy. The positivity rate of synovial fluid culture was higher in cases with previous antimicrobial therapy. The positivity rates of mNGS in synovial fluid decreased as the antimicrobial-free interval ranged from 4 to 14 days to 0 to 3 days. Conclusion: mNGS is more advantageous than culture with a higher pathogen detection rate. However, our data suggested that antimicrobial agents may need to be discontinued more than 3 days before sampling to further increase the positivity rate of mNGS for PJIs.

The role of ageing and oxidative stress in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is the primary cause of intervertebral disc (IVD) disease. With the increased ageing of society, an increasing number of patients are plagued by intervertebral disc disease. Ageing not only accelerates the decreased vitality and functional loss of intervertebral disc cells but also increases intracellular oxidative stress. Moreover, the speed of intervertebral disc ageing is also linked to high levels of reactive oxygen species (ROS) production. Not only is the production of ROS increased in ageing intervertebral disc cells, but antioxidant levels in degenerative intervertebral discs also decrease. In addition to the intervertebral disc, the structural components of the intervertebral disc matrix are vulnerable to oxidative damage. After chronic mitochondrial dysfunction, ROS can be produced in large quantities, while autophagy can eliminate these impaired mitochondria to reduce the production of ROS. Oxidative stress has a marked impact on the occurrence of IDD. In the future, IDD treatment is aiming to improve oxidative stress by regulating the redox balance in intervertebral disc cells. In summary, ageing and oxidative stress promote the degeneration of IVD, but further basic and clinical trials are needed to determine how to treat oxidative stress. At present, although there are many in-depth studies on the relationship between oxidative stress and degeneration of intervertebral disc cells, the specific mechanism has not been elucidated. In this paper, the main causes of intervertebral disc diseases are studied and summarized, and the impact of oxidative stress on intervertebral disc degeneration is studied.

Identifying hub circadian rhythm biomarkers and immune cell infiltration in rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with symptoms characterized by typical circadian rhythmic changes. This study aimed to identify the hub circadian rhythm genes (CRGs) in RA and explore their association with immune cell infiltration and pathogenesis of RA. Methods: The differentially expressed CRGs (DECRGs) between RA and normal control samples were screened from Datasets GSE12021 and GSE55235. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to explore the potential functional mechanisms of DECRGs in RA. Weighted Gene Co-expression Network Analysis and Least Absolute Shrinkage and Selection Operator regression analysis were performed to identify hub CRGs of RA. CIBERSORT was conducted to compare the infiltration level of immune cells in RA and control synovial tissue and their relationship with hub genes. In addition, the diagnostic value of hub biomarkers was evaluated by the area under the receiver operator characteristic curve. Further, a nomogram prediction model was constructed and its significance for clinical decision-making was evaluated. Results: The green module was identified as the hub module associated with RA. Four hub CRGs (EGR1, FOSL2, GADD45B, and NFIL3) were identified and showed that they had the highest specificity and sensitivity for RA diagnosis, respectively. The expression levels and diagnostic values of these genes were externally validated in the dataset GSE55457. A nomogram prediction model based on the four hub CRGs was constructed and proved to have a certain clinical decision value. Additionally, the correlation analysis of immune cells with hub genes showed that all hub genes were significantly positively correlated with activated mast cells, resting memory CD4+ T cells, and monocytes. Whereas, all hub genes were negatively correlated with plasma cells, CD8+ T cells, and activated memory CD4+ T cells. Meanwhile, FOSL2 and GADD45B were negatively correlated with Tfh cells. Conclusion: Four hub CRGs were identified and showed excellent diagnostic value for RA. These genes may be involved in the pathological process of RA by disrupting the rhythmic oscillations of cytokines through immune-related pathways and could be considered molecular targets for future chronotherapy against RA.

Hotspots and future directions in rheumatoid arthritis-related cardiovascular disease: A scientometric and visualization study from 2001 to 2021 based on Web of Science.

Background: The morbidity and mortality of cardiovascular diseases (CVD) in patients with rheumatoid arthritis (RA) is significantly higher than those in the general population, leading to RA-related CVD has attracted broad attention and numerous articles have been published. However, no study has systematically examined this area from a scientometric perspective. This study aimed to visualize the knowledge structure and identify emerging research trends and potential hotspots in this field. Materials and methods: Articles and reviews on RA-CVD published from 2001 to 2021 were extracted from the Web of Science Core Collection database. CiteSpace and VOSviewer software were used to visualize the knowledge network of countries, institutions, authors, references and keywords in this field. SPSS and Microsoft Excel software were used for curve fitting and correlation analysis. Results: A total of 2,618 articles and reviews were included. The number of publications about RA-related CVD significantly increased yearly. Publications were mainly concentrated in North America, Europe and East Asia. The United States contributed most with 699 publications, followed by the United Kingdom and Italy. Gross Domestic Product was an important factor affecting scientific output. University of Manchester and Professor Kitas George D. were the most prolific institutions and influential authors, respectively. Journal of Rheumatology was the most productive journal for RA-related CVD research. The research hotspots switched in the order of clinical features (cardiovascular events), mechanism exploration, anti-tumor necrosis factor therapy, risk factors, and antirheumatic drug safety, which can be observed from the keyword analysis and co-cited reference cluster analysis. Conclusions: This study found that research on RA-related CVD is flourishing. The safety and cardiovascular pharmacological mechanisms of anti-rheumatoid drugs, especially targeted synthetic DMARDs, would be the focus of current research and developmental trends in future research.

Global Research Status and Trends in Venous Thromboembolism After Hip or Knee Arthroplasty From 1990 to 2021: A Bibliometric Analysis.

Background: Venous thromboembolism (VTE) after hip or knee arthroplasty has attracted increasing attention over the past few decades. However, there is no bibliometric report on the publications in this field. The purpose of this study was to analyze the global research status, hotspots, and trends in VTE after arthroplasty. Methods: All articles about VTE research after hip or knee arthroplasty from 1990 to 2021 were retrieved from the Web of Science Core Collection database. The information of each article including citation, title, author, journal, country, institution, keywords, and level of evidence was extracted for bibliometric analysis. Results: A total of 1,245 original articles from 53 countries and 603 institutions were retrieved. The USA contributed most with 457 articles, followed by England and Canada. McMaster University in Canada was the leading institution for publications. The journals with the highest output and citation were the Journal of Arthroplasty and the Thrombosis and Haemostasis, respectively. The median number of citations was significantly different among the levels of evidence (F = 128.957, P < 0.001). The research hotspots switched from VTE diagnosis and heparin to factor Xa inhibitors (fondaparinux, rivaroxaban, apixaban) and direct thrombin inhibitors (dabigatran etexilate, ximelagatran), and finally to aspirin, risk factor studies, which can be observed from the keyword analysis and co-cited reference cluster analysis. Conclusions: This study observed an increasing trend of research articles on VTE after arthroplasty. Publications with higher levels of evidence gained further popularity among researchers and orthopedic surgeons. Additionally, individualized VTE prevention and the development of new, safe, effective, and inexpensive oral agents would be emerging trends in the future.

SdrG gene activated joint surface membrane protein PTPRJ to induce periprosthetic joint infection after total hip arthroplasty.

WHAT IS KNOWN AND OBJECTIVE: Up to now, no study focused on the role of SdrG in PJI after THA. To explore the mechanism of periprosthetic joint infection (PJI) after total hip arthroplasty (THA). METHODS: Joint fluid and blood were collected from patients with PJI after THA, aseptic loosening of the joints or bacterial infection after traumatic fractures of the extremities alone. The expression of SdrG in the 3 groups was determined by agarose gel electrophoresis. The expression of protein tyrosine phosphatase receptor J (PTPRJ) was measured by immunohistochemistry method. The platelet adhesion rate was determined by biochemical analysis. The content of D-dimer, CRP and ESR in blood was determined by latex agglutination method. Multiple linear correlation analysis was used to analyse the correlation between PJI and the expression of PTPRJ protein, platelet adhesion rate, D-dimer content, CRP and ESR. RESULTS AND DISCUSSION: The expression of SdrG and PTPRJ in PJI group was markedly increased compared to the other 2 groups. The platelet adhesion rate in PJI group was markedly larger compared to aseptic loosening and simple wound infection group, and the rate in simple wound infection group was larger than aseptic loosening group. The level of D-dimer, CRP and ESR in PJI group was higher than that of the other groups. The expression of PTPRJ protein, D-dimer content, CRP and ESR was all closely related to PJI, while platelet adhesion rate had no correlation with PJI. WHAT IS NEW AND CONCLUSION: SDRG gene around joint prosthesis was over-expressed, which activated joint surface membrane protein PTPRJ and then induced platelet aggregation to reduce joint function.

Vitamin E-Enhanced Liners in Primary Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.

OBJECTIVE: Adding vitamin E to highly cross-linked polyethylene liners is frequently performed in clinical practice, aiming at reducing liner wear, increasing liner survival, and delaying revision surgery. This study is aimed at evaluating the revision rate, total femoral head penetration, and postoperative clinical function of highly cross-linked polyethylene liners with and without vitamin E in total hip arthroplasty. METHODS: We conducted a systematic literature search to identify the use of highly cross-linked vitamin E liners compared to other liners in patients who received total hip arthroplasty (THA) before April 2021. The study quality assessment and data collection were conducted by two independent reviewers. Studies were artificially grouped, and vitamin E-enhanced liners (VE-PE) were compared with vitamin E-free liners (non-VE-PE). Analyses were executed using Review Manager version 5.4.1. RESULTS: From the preliminary screening of 568 studies, fourteen studies met the research criteria. Compared to non-VE-PE, using VE-PE reduced the all-cause revision rate (odds ratio = 0.54; 95% confidence interval (CI) 0.40, 0.73; P < 0.0001). The total femoral head penetration of the VE-PE was lower than that of the non-VE-PE (mean difference = -0.10; 95% CI -0.17, -0.03; P = 0.007). However, there was no difference in clinical function, including the Harris Hip Score and EuroQol Five-Dimension Questionnaire scores. CONCLUSION: Compared to the liners without vitamin E, the addition of vitamin E to liners could reduce the all-cause revision rate by approximately 46% in the short-term follow-up. In addition, even though addition of vitamin E could also slow down femoral head penetration, there is no contribution to clinical function.

The Top 100 Cited Articles in Osteonecrosis of the Femoral Head: A Bibliometric Analysis.

BACKGROUND: The number of articles of clinical and basic research for osteonecrosis of the femoral head (ONFH) is increasing, yet, to our knowledge, there is still a lack of bibliometric analysis on ONFH articles. The purpose of this study was to identify the top 100 cited (T100) articles related to ONFH research and to analyze the characteristics and qualities of these articles. METHODS: The T100 articles on ONFH were retrieved from the Web of Science database. The information about each article including citations, titles, authors, journals, countries, institutions, and keywords was recorded for bibliometric analysis. RESULTS: The T100 articles related to ONFH were mainly published from 1991 to 2010 (n = 70) and were originated from 24 countries. The USA, China, and Japan were the most productive countries in this regard. The most prolific institution was the University of Pennsylvania from the USA with 6 publications and 742 citations. The most cited article was published in 1995 by Professor Steinberg ME. The five most frequently occurring keywords were "femoral head," "osteonecrosis," "core decompression," "total hip arthroplasty," and "follow up." The keywords like "bone tissue engineering" and "extracorporeal shock wave" have emerged in recent years. CONCLUSIONS: The USA, China, and Japan contributed greatly in terms of the T100 articles. The outcomes of core decompression and total hip arthroplasty gathered the most research interests. In recent years, bone tissue engineering and extracorporeal shock wave have become new trends. However, the mechanism of ONFH is still unclear.

The Role of Preoperative Computed Tomography on the Quality of Reduction and Outcomes in Intertrochanteric Fracture: A Controlled Trial.

PURPOSE: The study is aimed at assessing the role of preoperative computerised tomography (CT) examination in the quality of reduction and outcomes in elderly patients with intertrochanteric fracture. METHODS: The elderly patients with an intertrochanteric fracture who were treated with proximal femoral nail antirotation were included. The patients were divided into the CT group and the no-CT group according to the presence of preoperative CT examination. Patients' baseline characteristics, quality of reduction, and function were recorded at follow-up. Functional outcomes were evaluated using the Harris hip scores (HHS). RESULTS: Totally, the study included 182 patients with intertrochanteric fractures, with 85 in the CT group and 97 in the no-CT group, admitted between January 2018 and June 2019. There was no difference in the quality of reduction, HHS, the fracture healing, or postoperative complications between the CT group and the no-CT group. However, the CT group experienced the shorter mean operative time and blood transfusion, compared to the no-CT group. CONCLUSIONS: The preoperative CT examination seems to be excessive for elderly patients with an intertrochanteric fracture.

The effect of the necrotic area on the biomechanics of the femoral head - a finite element study.

BACKGROUND: Femoral head collapse is the key to the progress of osteonecrosis of the femoral head (ONFH), but the causes of collapse are not completely clear. The better understanding of the progress of femoral head collapse will guide the treatment strategy for ONFH patients. The purpose of this study was to evaluate the biomechanical influence of necrosis area on the collapse of the femoral head by finite element analysis. METHODS: CT and MRI data from the hip joint of a healthy volunteer were collected to establish a finite element (FE) model of a normal hip. Subsequently, five categories of osteonecrosis FE models were established by using the normal model and computer software according to China-Japan Friendship Hospital (CJFH) classification for ONFH. The CJFH system includes five types based on the size and location of necrosis lesions in the femoral head (type M, C, L1, L2, and L3) and the stage of ONFH. The collapse indices of each model were analyzed by FE method, including the displacement, peak von Mises stress and stress index of the simulated necrotic area as well as the lateral pillar contact area of the femoral head to acetabular. RESULTS: (1) The displacement increments in the simulated necrotic areas of type M, C, L1, L2, and L3 models were 3.75 µm, 8.24 µm, 8.47 µm, 18.42 µm, and 20.44 µm respectively; the peak von Mises stress decrements were 1.50 MPa, 3.74 MPa, 3.73 MPa, 4.91 MPa, and 4.92 MPa respectively; and the stress indices were 0.04, 0.08, 0.08, 0.27, and 0.27 respectively. (2) The displacement increments in the lateral pillar contact areas of five type models were significantly different (P < 0.001) and increased in sequence as follows: 1.93 ± 0.15 µm, 5.74 ± 0.92 µm, 5.84 ± 1.42 µm, 14.50 ± 3.00 µm, and 16.43 ± 3.05 µm. The peak von Mises stress decrements were also significantly different (P < 0.001) and increased in sequence as follows: 0.52 ± 0.30 MPa, 0.55 ± 0.12 MPa, 0.67 ± 0.33 MPa, 4.17 ± 0.59 MPa, and 4.19 ± 0.60 MPa. (3) The collapse indices including the displacement increments and peak von Mises stress decrements of type L2 and L3 models were markedly higher than those of type M, C, and L1 models (P < 0.001). CONCLUSIONS: The collapse indices of the femoral heads of type L2 and L3 FE models were significantly higher than those of type M, C, and L1. Different areas of necrosis result in varied impact on the femoral head collapse.

Antagonism of cysteinyl leukotriene receptor 1 (cysLTR1) by montelukast suppresses cell senescence of chondrocytes.

Aging is closely associated with osteoarthritis (OA). Although its underlying mechanisms remain unknown, cellular senescence in chondrocytes has become an important therapeutic target for the treatment of OA. Cysteinyl leukotriene receptors (cysLTRs) mediate the pathobiological function of cysteinyl leukotrienes (cysLTs). However, the roles of cysLTRs in the pathogenesis of OA have not been reported before. In the current study, we found that cysLTR1 but not cysLTR2 is expressed in human primary chondrocytes. In addition, stimulation with tumor necrosis factor α (TNF-α) resulted in a significant increase in the expression of cysLTR1. Interestingly, montelukast, a specific cysLTR1 antagonist, attenuated TNF-α-induced up-regulation of the activity of senescence-associated ß-galactosidase (SA-ß-Gal). In addition, TNF-α led to cell cycle arrest at the G0/G1 phase, which was prevented by treatment with montelukast. Notably, montelukast reduced expression of the senescence markers p53, p21 and PAI-1. In addition, montelukast ameliorated TNF-α-induced K382 acetylation of p53 by promoting the expression of SIRT1. Silencing of SIRT1 using SIRT1 siRNA broke the inhibitory effects of montelukast on K382 acetylation of p53. Importantly, silencing of cysLTR1 reversed the reduction of SIRT1 expression as well as the K382 acetylation of p53. Our findings strongly implicate that cysLTR1 has the capacity to regulate cellular senescence in chondrocytes. It is suggested that montelukast may be a potential therapeutic agent for chondro-protective therapy.