Aims. This study aimed to explore the role of small colony
Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI. Cite this article:
The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 ( Chinese patients with OP were recruited between March 2011 and December 2015 from our hospital. In this study, a total of 1267 post-menopausal female patients (631 OP patients and 636 control patients) were selected. The mean age of all subjects was 69.2 years (sd 15.8). A generalized multifactor dimensionality reduction (GMDR) model and logistic regression model were used to examine the interaction between SNP and obesity on OP. For OP patient-control haplotype analyses, the SHEsis online haplotype analysis software (Objectives
Methods
Aims. Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory
Aims. The cemented Oxford unicompartmental knee arthroplasty (OUKA) features two
Aims. Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. Methods. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP
Research into COVID-19 has been rapid in response to the dynamic global situation, which has resulted in heterogeneity of methodology and the communication of information. Adherence to reporting standards would improve the quality of evidence presented in future studies, and may ensure that findings could be interpreted in the context of the wider literature. The COVID-19 pandemic remains a dynamic situation, requiring continued assessment of the disease incidence and monitoring for the emergence of viral
Aims. There is ambiguity surrounding the degree of scaphoid union required to safely allow mobilization following scaphoid waist fracture. Premature mobilization could lead to refracture, but late mobilization may cause stiffness and delay return to normal function. This study aims to explore the risk of refracture at different stages of scaphoid waist fracture union in three common fracture patterns, using a novel finite element method. Methods. The most common anatomical
Aims. Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations. Methods. Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases. Results. MDD has a significant genetic correlation with OA (r. g. = 0.29) and the two diseases share a considerable proportion of causal
Aims. The new COVID-19
Aims. As the world continues to fight successive waves of COVID-19
Objectives. Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations. Methods. We systematically genotyped rs8044769 and evaluated the association between the genetic
Objectives. Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA. Methods. We systematically screened three tagging polymorphisms (rs182052, rs2082940 and rs6773957) in the ADIPOQ gene, and evaluated the association between the genetic
Objectives. It has been hypothesized that patellofemoral pain, a common knee condition in adolescents and young adults, may be a precursor of degenerative joint changes and may ultimately lead to patellofemoral osteoarthritis. Since both conditions share several mechanical disease characteristics, such as altered contact area between the femur and patella and increased joint stress, we investigated whether these conditions share similar and different shape characteristics of the patella compared with normal controls. Methods. This cross-sectional study compared three different study populations: 32 patellofemoral pain subjects (mean age, 32 years (22 to 45); 72% female); 56 isolated radiological patellofemoral osteoarthritis subjects (mean age, 54 years (44 to 58); 89% female); and 80 healthy control subjects (mean age, 52 years (44 to 58); 74% female). Measurements included questionnaires, and lateral and skyline radiographs of the knee. Two separate 30-point 2D statistical shape models of the patella were created from the lateral and skyline radiographs. A general linear model was used to test for differences in standardized shape modes (a specific shape
Objectives. Overlap between the distal tibia and fibula has always been quoted
to be positive. If the value is not positive then an injury to the
syndesmosis is thought to exist. Our null hypothesis is that it
is a normal
Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.Aims
Methods
A novel enhanced cement fixation (EF) tibial implant with deeper cement pockets and a more roughened bonding surface was released to market for an existing total knee arthroplasty (TKA) system.This randomized controlled trial assessed fixation of the both the EF (ATTUNE S+) and standard (Std; ATTUNE S) using radiostereometric analysis. Overall, 50 subjects were randomized (21 EF-TKA and 23 Std-TKA in the final analysis), and had follow-up visits at six weeks, and six, 12, and 24 months to assess migration of the tibial component. Low viscosity bone cement with tobramycin was used in a standardized fashion for all subjects. Patient-reported outcome measure data was captured at preoperative and all postoperative visits.Aims
Methods
Patients with A1 and A2 trochanteric hip fractures represent a substantial proportion of trauma caseload, and national guidelines recommend that sliding hip screws (SHS) should be used for these injuries. Despite this, intramedullary nails (IMNs) are routinely implanted in many hospitals, at extra cost and with unproven patient outcome benefit. We have used data from the National Hip Fracture Database (NHFD) to examine the use of SHS and IMN for A1 and A2 hip fractures at a national level, and to define the cost implications of management decisions that run counter to national guidelines. We used the NHFD to identify all operations for fixation of trochanteric fractures in England and Wales between 1 January 2021 and 31 December 2021. A uniform price band from each of three hip fracture implant manufacturers was used to set cost implications alongside variation in implant use.Aims
Methods
Instability is a common cause of failure after total hip arthroplasty. A novel reverse total hip has been developed, with a femoral cup and acetabular ball, creating enhanced mechanical stability. The purpose of this study was to assess the implant fixation using radiostereometric analysis (RSA), and the clinical safety and efficacy of this novel design. Patients with end-stage osteoarthritis were enrolled in a prospective cohort at a single centre. The cohort consisted of 11 females and 11 males with mean age of 70.6 years (SD 3.5) and BMI of 31.0 kg/m2 (SD 5.7). Implant fixation was evaluated using RSA as well as Western Ontario and McMaster Universities Osteoarthritis Index, Harris Hip Score, Oxford Hip Score, Hip disability and Osteoarthritis Outcome Score, 38-item Short Form survey, and EuroQol five-dimension health questionnaire scores at two-year follow-up. At least one acetabular screw was used in all cases. RSA markers were inserted into the innominate bone and proximal femur with imaging at six weeks (baseline) and six, 12, and 24 months. Independent-samples Aims
Methods
Despite higher rates of revision after total hip arthroplasty (THA) being reported for uncemented stems in patients aged > 75 years, they are frequently used in this age group. Increased mortality after cemented fixation is often used as a justification, but recent data do not confirm this association. The aim of this study was to investigate the influence of the design of the stem and the type of fixation on the rate of revision and immediate postoperative mortality, focusing on the age and sex of the patients. A total of 333,144 patients with primary osteoarthritis (OA) of the hip who underwent elective THA between November 2012 and September 2022, using uncemented acetabular components without reconstruction shells, from the German arthroplasty registry were included in the study. The revision rates three years postoperatively for four types of stem (uncemented, uncemented with collar, uncemented short, and cemented) were compared within four age groups: < 60 years (Young), between 61 and 70 years (Mid-I), between 71 and 80 years (Mid-II), and aged > 80 years (Old). A noninferiority analysis was performed on the most frequently used designs of stem.Aims
Methods
Unicompartmental and total knee arthroplasty (UKA and TKA) are successful treatments for osteoarthritis, but the solid metal implants disrupt the natural distribution of stress and strain which can lead to bone loss over time. This generates problems if the implant needs to be revised. This study investigates whether titanium lattice UKA and TKA implants can maintain natural load transfer in the proximal tibia. In a cadaveric model, UKA and TKA procedures were performed on eight fresh-frozen knee specimens, using conventional (solid) and titanium lattice tibial implants. Stress at the bone-implant interfaces were measured and compared to the native knee.Aims
Methods
Our objective was describing an algorithm to identify and prevent vascular injury in patients with intrapelvic components. Patients were defined as at risk to vascular injuries when components or cement migrated 5 mm or more beyond the ilioischial line in any of the pelvic incidences (anteroposterior and Judet view). In those patients, a serial investigation was initiated by a CT angiography, followed by a vascular surgeon evaluation. The investigation proceeded if necessary. The main goal was to assure a safe tissue plane between the hardware and the vessels.Aims
Methods
There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO4) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO4 applied locally to treat ODAI. A total of 30 operations with ceftriaxone-loaded CaSO4 had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS).Aims
Methods
Precise implant positioning, tailored to individual spinopelvic biomechanics and phenotype, is paramount for stability in total hip arthroplasty (THA). Despite a few studies on instability prediction, there is a notable gap in research utilizing artificial intelligence (AI). The objective of our pilot study was to evaluate the feasibility of developing an AI algorithm tailored to individual spinopelvic mechanics and patient phenotype for predicting impingement. This international, multicentre prospective cohort study across two centres encompassed 157 adults undergoing primary robotic arm-assisted THA. Impingement during specific flexion and extension stances was identified using the virtual range of motion (ROM) tool of the robotic software. The primary AI model, the Light Gradient-Boosting Machine (LGBM), used tabular data to predict impingement presence, direction (flexion or extension), and type. A secondary model integrating tabular data with plain anteroposterior pelvis radiographs was evaluated to assess for any potential enhancement in prediction accuracy.Aims
Methods
Custom-made partial pelvis replacements (PPRs) are increasingly used in the reconstruction of large acetabular defects and have mainly been designed using a triflange approach, requiring extensive soft-tissue dissection. The monoflange design, where primary intramedullary fixation within the ilium combined with a monoflange for rotational stability, was anticipated to overcome this obstacle. The aim of this study was to evaluate the design with regard to functional outcome, complications, and acetabular reconstruction. Between 2014 and 2023, 79 patients with a mean follow-up of 33 months (SD 22; 9 to 103) were included. Functional outcome was measured using the Harris Hip Score and EuroQol five-dimension questionnaire (EQ-5D). PPR revisions were defined as an endpoint, and subgroups were analyzed to determine risk factors.Aims
Methods
To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment. Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue.Aims
Methods
The aim of this study is to determine the predictors of overall survival (OS) and predictive factors of poor prognosis of conventional high-grade osteosarcoma of the limbs in a single-centre in South Africa. We performed a retrospective cross-sectional analysis to identify the prognostic factors that predict the OS of patients with histologically confirmed high-grade conventional osteosarcoma of the limbs over ten years. We employed the Cox proportional regression model and the Kaplan-Meier method for statistical analysis.Aims
Methods
The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA. Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database.Aims
Methods
This study aimed to investigate the risk of postoperative complications in COVID-19-positive patients undergoing common orthopaedic procedures. Using the National Surgical Quality Improvement Programme (NSQIP) database, patients who underwent common orthopaedic surgery procedures from 1 January to 31 December 2021 were extracted. Patient preoperative COVID-19 status, demographics, comorbidities, type of surgery, and postoperative complications were analyzed. Propensity score matching was conducted between COVID-19-positive and -negative patients. Multivariable regression was then performed to identify both patient and provider risk factors independently associated with the occurrence of 30-day postoperative adverse events.Aims
Methods
Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines.Aims
Methods
This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.Aims
Methods
Ankle fracture is one of the most common musculoskeletal injuries sustained in the UK. Many patients experience pain and physical impairment, with the consequences of the fracture and its management lasting for several months or even years. The broad aim of ankle fracture treatment is to maintain the alignment of the joint while the fracture heals, and to reduce the risks of problems, such as stiffness. More severe injuries to the ankle are routinely treated surgically. However, even with advances in surgery, there remains a risk of complications; for patients experiencing these, the associated loss of function and quality of life (Qol) is considerable. Non-surgical treatment is an alternative to surgery and involves applying a cast carefully shaped to the patient’s ankle to correct and maintain alignment of the joint with the key benefit being a reduction in the frequency of common complications of surgery. The main potential risk of non-surgical treatment is a loss of alignment with a consequent reduction in ankle function. This study aims to determine whether ankle function, four months after treatment, in patients with unstable ankle fractures treated with close contact casting is not worse than in those treated with surgical intervention, which is the current standard of care. This trial is a pragmatic, multicentre, randomized non-inferiority clinical trial with an embedded pilot, and with 12 months clinical follow-up and parallel economic analysis. A surveillance study using routinely collected data will be performed annually to five years post-treatment. Adult patients, aged 60 years and younger, with unstable ankle fractures will be identified in daily trauma meetings and fracture clinics and approached for recruitment prior to their treatment. Treatments will be performed in trauma units across the UK by a wide range of surgeons. Details of the surgical treatment, including how the operation is done, implant choice, and the recovery programme afterwards, will be at the discretion of the treating surgeon. The non-surgical treatment will be close-contact casting performed under anaesthetic, a technique which has gained in popularity since the publication of the Ankle Injury Management (AIM) trial. In all, 890 participants (445 per group) will be randomly allocated to surgical or non-surgical treatment. Data regarding ankle function, QoL, complications, and healthcare-related costs will be collected at eight weeks, four and 12 months, and then annually for five years following treatment. The primary outcome measure is patient-reported ankle function at four months from treatment.Aims
Methods
Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients. Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR).Aims
Methods
Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD. A total of 3,321 independent loci of gut microbiota were used to calculate the individual polygenic risk score (PRS) for 114 gut microbiota-related traits. The individual genotype data were obtained from UK Biobank cohort. Linear regressions were then conducted to evaluate the possible association of gut microbiota with L1-L4 BMD (n = 4,070), total BMD (n = 4,056), and femur total BMD (n = 4,054), respectively. PLINK 2.0 was used to detect the single-nucleotide polymorphism (SNP) × gut microbiota interaction effect on the risks of L1-L4 BMD, total BMD, and femur total BMD, respectively.Aims
Methods
Bone regeneration during treatment of staphylococcal bone infection is challenging due to the ability of The human osteoblast-like Saos-2 cells infected with Aims
Methods
Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 ( We examined vulnerability of Aims
Methods
The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA). Based on the genome-wide association studies (GWAS) summary statistics of RA from European descent and the GWAS summary datasets of 3,622 plasma proteins, we explored the relationship between RA and plasma proteins from three aspects. First, linkage disequilibrium score regression (LD score regression) was applied to detect the genetic correlation between RA and plasma proteins. Mendelian randomization (MR) analysis was then used to evaluate the causal association between RA and plasma proteins. Finally, GEO2R was used to screen the differentially expressed genes (DEGs) between patients with RA and healthy controls.Aims
Methods
Recurrent dislocation is both a cause and consequence of glenoid bone loss, and the extent of the bony defect is an indicator guiding operative intervention. Literature suggests that loss greater than 25% requires glenoid reconstruction. Measuring bone loss is controversial; studies use different methods to determine this, with no clear evidence of reproducibility. A systematic review was performed to identify existing CT-based methods of quantifying glenoid bone loss and establish their reliability and reproducibility A Preferred Reporting Items for Systematic reviews and Meta-Analyses-compliant systematic review of conventional and grey literature was performed.Aims
Methods
The aim of this study was to screen the entire genome for genetic markers associated with risk for anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injury. Genome-wide association (GWA) analyses were performed using data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. ACL and PCL injury cases were identified based on electronic health records from KPRB and the UK Biobank. GWA analyses from both cohorts were tested for ACL and PCL injury using a logistic regression model adjusting for sex, height, weight, age at enrolment, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNPs). The data from the two GWA studies were combined in a meta-analysis. Candidate genes previously reported to show an association with ACL injury in athletes were also tested for association from the meta-analysis data from the KPRB and the UK Biobank GWA studies.Aims
Methods
Elective orthopaedic surgery was cancelled early in the COVID-19 pandemic and is currently running at significantly reduced capacity in most institutions. This has resulted in a significant backlog to treatment, with some hospitals projecting that waiting times for arthroplasty is three times the pre-COVID-19 duration. There is concern that the patient group requiring arthroplasty are often older and have more medical comorbidities—the same group of patients advised they are at higher risk of mortality from catching COVID-19. The aim of this study is to investigate the morbidity and mortality in elective patients operated on during the COVID-19 pandemic and compare this to a pre-pandemic cohort. Primary outcome was 30-day mortality. Secondary outcomes were perioperative complications, including nosocomial COVID-19 infection. These operations were performed in a district general hospital, with COVID-19 acute admissions in the same building. Our institution reinstated elective operations using a “Blue stream” pathway, which involves isolation before and after surgery, COVID-19 testing pre-admission, and separation of ward and theatre pathways for “blue” patients. A register of all arthroplasties was taken, and their clinical course and investigations recorded.Aims
Methods
There is little published on the outcomes after restarting elective orthopaedic procedures following cessation of surgery due to the COVID-19 pandemic. During the pandemic, the reported perioperative mortality in patients who acquired SARS-CoV-2 infection while undergoing elective orthopaedic surgery was 18% to 20%. The aim of this study is to report the surgical outcomes, complications, and risk of developing COVID-19 in 2,316 consecutive patients who underwent elective orthopaedic surgery in the latter part of 2020 and comparing it to the same, pre-pandemic, period in 2019. A retrospective service evaluation of patients who underwent elective surgical procedures between 16 June 2020 and 12 December 2020 was undertaken. The number and type of cases, demographic details, American society of Anesthesiologists (ASA) grade, BMI, 30-day readmission rates, mortality, and complications at one- and six-week intervals were obtained and compared with patients who underwent surgery during the same six-month period in 2019.Aims
Methods
The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular musculoskeletal research, and will conclude by speculating what the future holds for the use of CRISPR-related treatments and therapies in clinical orthopaedic practice. Cite this article:
Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article:
Femoroacetabular impingement (FAI) describes abnormal bony contact of the proximal femur against the acetabulum. The term was first coined in 1999; however what is often overlooked is that descriptions of the morphology have existed in the literature for centuries. The aim of this paper is to delineate its origins and provide further clarity on FAI to shape future research. A non-systematic search on PubMed was performed using keywords such as “impingement” or “tilt deformity” to find early anatomical descriptions of FAI. Relevant references from these primary studies were then followed up.Aims
Methods
This study aimed to investigate the effect of ATDC5 chondrocytes were cultured in insulin-transferrin-selenium medium to induce differentiation. Cells were transfected with pcDNA3.0 plasmids with either a wild-type (WT) or mutated (MUT) Aims
Methods
Osteoarthritis (OA) is the most prevalent joint disease. However, the specific and definitive genetic mechanisms of OA are still unclear. Tissue-related transcriptome-wide association studies (TWAS) of hip OA and knee OA were performed utilizing the genome-wide association study (GWAS) data of hip OA and knee OA (including 2,396 hospital-diagnosed hip OA patients versus 9,593 controls, and 4,462 hospital-diagnosed knee OA patients versus 17,885 controls) and gene expression reference to skeletal muscle and blood. The OA-associated genes identified by TWAS were further compared with the differentially expressed genes detected by the messenger RNA (mRNA) expression profiles of hip OA and knee OA. Functional enrichment and annotation analysis of identified genes was performed by the DAVID and FUMAGWAS tools.Aims
Methods
Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical and chronic polyarthritis. Fibroblast-like synoviocytes are mainly involved in joint inflammation and cartilage and bone destruction by inflammatory cytokines and matrix-degrading enzymes in RA. Approaches that induce various cellular growth alterations of synoviocytes are considered as potential strategies for treating RA. However, since synoviocytes play a critical role in RA, the mechanism and hyperplastic modulation of synoviocytes and their motility need to be addressed. In this review, we focus on the alteration of synoviocyte signalling and cell fate provided by signalling proteins, various antioxidant molecules, enzymes, compounds, clinical candidates, to understand the pathology of the synoviocytes, and finally to achieve developed therapeutic strategies of RA. Cite this article:
Cementless knee arthroplasty has seen a recent resurgence in popularity due to conceptual advantages, including improved osseointegration providing biological fixation, increased surgical efficiency, and reduced systemic complications associated with cement impaction and wear from cement debris. Increasingly younger and higher demand patients are requiring knee arthroplasty, and as such, there is optimism cementless fixation may improve implant survivorship and functional outcomes. Compared to cemented implants, the National Joint Registry (NJR) currently reports higher revision rates in cementless total knee arthroplasty (TKA), but lower in unicompartmental knee arthroplasty (UKA). However, recent studies are beginning to show excellent outcomes with cementless implants, particularly with UKA which has shown superior performance to cemented varieties. Cementless TKA has yet to show long-term benefit, and currently performs equivalently to cemented in short- to medium-term cohort studies. However, with novel concepts including 3D-printed coatings, robotic-assisted surgery, radiostereometric analysis, and kinematic or functional knee alignment principles, it is hoped they may help improve the outcomes of cementless TKA in the long-term. In addition, though cementless implant costs remain higher due to novel implant coatings, it is speculated cost-effectiveness can be achieved through greater surgical efficiency and potential reduction in revision costs. There is paucity of level one data on long-term outcomes between fixation methods and the cost-effectiveness of modern cementless knee arthroplasty. This review explores recent literature on cementless knee arthroplasty, with regards to clinical outcomes, implant survivorship, complications, and cost-effectiveness; providing a concise update to assist clinicians on implant choice. Cite this article:
Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method. We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets.Aims
Methods
Modern metal-on-metal (MoM) hip resurfacing arthroplasty (HRA), while achieving good results with well-orientated, well-designed components in ideal patients, is contraindicated in women, men with head size under 50 mm, or metal hypersensitivity. These patients currently have no access to the benefits of HRA. Highly crosslinked polyethylene (XLPE) has demonstrated clinical success in total hip arthroplasty (THA) and, when used in HRA, potentially reduces metal ion-related sequelae. We report the early performance of HRA using a direct-to-bone cementless mono-bloc XLPE component coupled with a cobalt-chrome femoral head, in the patient group for whom HRA is currently contraindicated. This is a cross-sectional, observational assessment of 88 consecutive metal-on-XLPE HRAs performed in 84 patients between 2015 and 2018 in three centres (three surgeons, including the designer surgeon). Mean follow-up is 1.6 years (0.7 to 3.9). Mean age at operation was 56 years (Objectives
Methods
There has been a recent resurgence in interest in combined partial knee arthroplasty (PKA) as an alternative to total knee arthroplasty (TKA). The varied terminology used to describe these procedures leads to confusion and ambiguity in communication between surgeons, allied health professionals, and patients. A standardized classification system is required for patient safety, accurate clinical record-keeping, clear communication, correct coding for appropriate remuneration, and joint registry data collection. An advanced PubMed search was conducted, using medical subject headings (MeSH) to identify terms and abbreviations used to describe knee arthroplasty procedures. The search related to TKA, unicompartmental (UKA), patellofemoral (PFA), and combined PKA procedures. Surveys were conducted of orthopaedic surgeons, trainees, and biomechanical engineers, who were asked which of the descriptive terms and abbreviations identified from the literature search they found most intuitive and appropriate to describe each procedure. The results were used to determine a popular consensus.Aims
Materials and Methods
Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study. A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3.Objectives
Methods
Osteoporosis is a metabolic disease resulting in progressive loss of bone mass as measured by bone mineral density (BMD). Physical exercise has a positive effect on increasing or maintaining BMD in postmenopausal women. The contribution of exercise to the regulation of osteogenesis in osteoblasts remains unclear. We therefore investigated the effect of exercise on osteoblasts in ovariectomized mice. We compared the activity of differentially expressed genes of osteoblasts in ovariectomized mice that undertook exercise (OVX+T) with those that did not (OVX), using microarray and bioinformatics.Objectives
Methods
Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients’ BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05.Objectives
Method
Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis. Microarray data sets GSE56815 and GSE56814, comprising 67 osteoporosis blood samples and 62 control blood samples, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in osteoporosis using Limma package (3.2.1) and Meta-MA packages. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify biological functions. Furthermore, the transcriptional regulatory network was established between the top 20 DEGs and transcriptional factors using the UCSC ENCODE Genome Browser. Receiver operating characteristic (ROC) analysis was applied to investigate the diagnostic value of several DEGs.Objectives
Methods
This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA). Knee joint synovial fluid samples were collected from 45 patients with OA of the knee (15 mild, 15 moderate and 15 severe), ten healthy volunteers, ten patients with gouty arthritis, and ten with rheumatoid arthritis. The Kellgren–Lawrence grading (KLG) was used to assess the radiological severity of knee OA, and the patients were stratified into mild (KLG < 2), moderate (KLG = 2), and severe (KLG > 2). The expression of miR-140-3p and miR-140-5p of individual samples was measured by SYBR Green quantitative polymerase chain reaction (PCR) analysis. The expression of miR-140-3p and miR-140-5p was normalised to U6 internal control using the 2-△△CT method. All data were processed using SPSS software.Objectives
Methods
The number of arthroplasties being performed
increases each year. Patients undergoing an arthroplasty are at
risk of venous thromboembolism (VTE) and appropriate prophylaxis
has been recommended. However, the optimal protocol and the best
agent to minimise VTE under these circumstances are not known. Although
many agents may be used, there is a difference in their efficacy
and the risk of bleeding. Thus, the selection of a particular agent relies
on the balance between the desire to minimise VTE and the attempt
to reduce the risk of bleeding, with its undesirable, and occasionally
fatal, consequences. Acetylsalicylic acid (aspirin) is an agent for VTE prophylaxis
following arthroplasty. Many studies have shown its efficacy in
minimising VTE under these circumstances. It is inexpensive and
well-tolerated, and its use does not require routine blood tests.
It is also a ‘milder’ agent and unlikely to result in haematoma
formation, which may increase both the risk of infection and the
need for further surgery. Aspirin is also unlikely to result in persistent
wound drainage, which has been shown to be associated with the use
of agents such as low-molecular-weight heparin (LMWH) and other
more aggressive agents. The main objective of this review was to summarise the current
evidence relating to the efficacy of aspirin as a VTE prophylaxis
following arthroplasty, and to address some of the common questions
about its use. There is convincing evidence that, taking all factors into account,
aspirin is an effective, inexpensive, and safe form of VTE following
arthroplasty in patients without a major risk factor for VTE, such
as previous VTE. Cite this article:
Excessive acetabular coverage is the most common cause of pincer-type
femoroacetabular impingement. To date, an association between acetabular
over-coverage and genetic variations has not been studied. In this
study we investigated the association between single nucleotide
polymorphisms (SNPs) of paralogous Homeobox (HOX)9 genes and acetabular
coverage in Japanese individuals to identify a possible genetic
variation associated with acetabular over-coverage. We investigated 19 total SNPs in the four HOX9 paralogs, then
focused in detail on seven of those located in the 3’ untranslated
region of Objectives
Methods
This study compared the primary stability of two commercially
available acetabular components from the same manufacturer, which
differ only in geometry; a hemispherical and a peripherally enhanced
design (peripheral self-locking (PSL)). The objective was to determine
whether altered geometry resulted in better primary stability. Acetabular components were seated with 0.8 mm to 2 mm interference
fits in reamed polyethylene bone substrate of two different densities
(0.22 g/cm3 and 0.45 g/cm3). The primary stability
of each component design was investigated by measuring the peak
failure load during uniaxial pull-out and tangential lever-out tests.Objective
Methods
The period of post-operative treatment before surgical wounds
are completely closed remains a key window, during which one can
apply new technologies that can minimise complications. One such
technology is the use of negative pressure wound therapy to manage
and accelerate healing of the closed incisional wound (incisional
NPWT). We undertook a literature review of this emerging indication
to identify evidence within orthopaedic surgery and other surgical
disciplines. Literature that supports our current understanding
of the mechanisms of action was also reviewed in detail. Objectives
Methods
Orthopaedic surgeons use stems in revision knee surgery to obtain
stability when metaphyseal bone is missing. No consensus exists
regarding stem size or method of fixation. This A custom test rig using differential variable reluctance transducers
(DVRTs) was developed to record all translational and rotational
motions at the bone–implant interface. Composite femurs were used.
These were secured to permit variation in flexion angle from 0°
to 90°. Cyclic loads were applied through a tibial component based
on three peaks corresponding to 0°, 10° and 20° flexion from a normal
walking cycle. Three different femoral components were investigated
in this study for cementless and cemented interface conditions.Objectives
Methods