In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.Aims
Methods
Frailty greatly increases the risk of adverse outcome of trauma in older people. Frailty detection tools appear to be unsuitable for use in traumatically injured older patients. We therefore aimed to develop a method for detecting frailty in older people sustaining trauma using routinely collected clinical data. We analyzed prospectively collected registry data from 2,108 patients aged ≥ 65 years who were admitted to a single major trauma centre over five years (1 October 2015 to 31 July 2020). We divided the sample equally into two, creating derivation and validation samples. In the derivation sample, we performed univariate analyses followed by multivariate regression, starting with 27 clinical variables in the registry to predict Clinical Frailty Scale (CFS; range 1 to 9) scores. Bland-Altman analyses were performed in the validation cohort to evaluate any biases between the Nottingham Trauma Frailty Index (NTFI) and the CFS.Aims
Methods
To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.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
Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive. Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis.Aims
Methods
Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA. OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot.Aims
Methods
Various surgical techniques have been described for total hip arthroplasty (THA) in patients with Crowe type III dislocated hips, who have a large acetabular bone defect. The aim of this study was to evaluate the long-term clinical results of patients in whom anatomical reconstruction of the acetabulum was performed using a cemented acetabular component and autologous bone graft from the femoral neck. A total of 22 patients with Crowe type III dislocated hips underwent 28 THAs using bone graft from the femoral neck between 1979 and 2000. A Charnley cemented acetabular component was placed at the level of the true acetabulum after preparation with bone grafting. All patients were female with a mean age at the time of surgery of 54 years (35 to 68). A total of 18 patients (21 THAs) were followed for a mean of 27.2 years (20 to 33) after the operation.Aims
Methods
Currently, the US Center for Medicaid and Medicare Services (CMS) has been testing bundled payments for revision total joint arthroplasty (TJA) through the Bundled Payment for Care Improvement (BPCI) programme. Under the BPCI, bundled payments for revision TJAs are defined on the basis of diagnosis-related groups (DRGs). However, these DRG-based bundled payment models may not be adequate to account appropriately for the varying case-complexity seen in revision TJAs. The 2008-2014 Medicare 5% Standard Analytical Files (SAF5) were used to identify patients undergoing revision TJA under DRG codes 466, 467, or 468. Generalized linear regression models were built to assess the independent marginal cost-impact of patient, procedural, and geographic characteristics on 90-day costs.Aims
Methods
Reverse shoulder arthroplasty (RSA) reliably improves shoulder pain and function for a variety of indications. However, the safety and efficacy of RSA in elderly patients is largely unknown. The purpose of this study was to report the mortality, morbidity, complications, reoperations, and outcomes of primary RSA in patients aged > 80 years. Between 2004 and 2013, 242 consecutive primary RSAs were performed in patients aged > 80 years (mean 83.3 years (Aims
Patients and Methods
The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA). The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both Objectives
Methods
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
The aims of this study were to determine the
functional impact and financial burden of isolated and recurrent dislocation
after total hip arthroplasty (THA). Our secondary goal was to determine
whether there was a difference between patients who were treated
non-operatively and those who were treated operatively. We retrospectively reviewed 71 patients who had suffered dislocation
of a primary THA. Their mean age was 67 years (41 to 92) and the
mean follow-up was 3.8 years (2.1 to 8.2). Because patients with recurrent dislocation were three times
more likely to undergo operative treatment (p <
0.0001), they
ultimately had a significantly higher mean Harris Hip Score (HHS)
(p = 0.0001), lower mean Western Ontario and McMaster Universities
Arthritis Index (WOMAC) scores (p = 0.001) and a higher mean SF-12
score (p <
0.0001) than patients with a single dislocation. Likewise,
those who underwent operative treatment had a higher mean HHS (p
<
0.0001), lower mean WOMAC score (p <
0.0001) and a higher
mean SF-12 score (p <
0.0001) than those who were treated non-operatively. Recurrent dislocation and operative treatment increased costs
by 300% (£11 456;
p <
0.0001) and 40% (£5217; p <
0.0001), respectively. The operative treatment of recurrent dislocation results in significantly
better function than non-operative management. Moreover, the increase
in costs for operative treatment is modest compared with that of
non-operative measures. Cite this article:
Salubrinal is a synthetic agent that elevates phosphorylation
of eukaryotic translation initiation factor 2 alpha (eIF2α) and
alleviates stress to the endoplasmic reticulum. Previously, we reported
that in chondrocytes, Salubrinal attenuates expression and activity
of matrix metalloproteinase 13 (MMP13) through downregulating nuclear
factor kappa B (NFκB) signalling. We herein examine whether Salubrinal
prevents the degradation of articular cartilage in a mouse model
of osteoarthritis (OA). OA was surgically induced in the left knee of female mice. Animal
groups included age-matched sham control, OA placebo, and OA treated
with Salubrinal or Guanabenz. Three weeks after the induction of
OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At
three and six weeks, the femora and tibiae were isolated and the sagittal
sections were stained with Safranin O.Objectives
Methods
We compared the length of hospitalisation, rate
of infection, dislocation of the hip and revision, and mortality following
primary hip and knee arthroplasty for osteoarthritis in patients
with
The purpose of this study was to assess N-acetyl aspartate changes
in the thalamus in patients with osteoarthritis of the hip using
proton magnetic resonance spectroscopy. Nine patients with osteoarthritis of the hip (symptomatic group,
nine women; mean age 61.4 years (48 to 78)) and nine healthy volunteers
(control group, six men, three women; mean age 30.0 years (26 to
38)) underwent proton magnetic resonance spectroscopy to assess
the changes of N-acetyl aspartate in the thalamus. Objectives
Methods
We compared revision and mortality rates of 4668
patients undergoing primary total hip and knee replacement between
1989 and 2007 at a University Hospital in New Zealand. The mean
age at the time of surgery was 69 years (16 to 100). A total of
1175 patients (25%) had died at follow-up at a mean of ten years
post-operatively. The mean age of those who died within ten years
of surgery was 74.4 years (29 to 97) at time of surgery. No change
in comorbidity score or age of the patients receiving joint replacement
was noted during the study period. No association of revision or
death could be proven with higher comorbidity scoring, grade of
surgeon, or patient gender. We found that patients younger than 50 years at the time of surgery
have a greater chance of requiring a revision than of dying, those
around 58 years of age have a 50:50 chance of needing a revision,
and in those older than 62 years the prosthesis will normally outlast
the patient. Patients over 77 years old have a greater than 90%
chance of dying than requiring a revision whereas those around 47
years are on average twice as likely to require a revision than
die. This information can be used to rationalise the need for long-term
surveillance and during the informed consent process.
The aim of this study was to determine the comorbid risk factors for failure in young patients who undergo fixation of a displaced fracture of the femoral neck. We identified from a prospective database all such patients ≤ 60 years of age treated with reduction and internal fixation. The main outcome measures were union, failure of fixation, nonunion and the development of avascular necrosis. There were 122 patients in the study. Union occurred in 83 patients (68%) at a mean follow-up of 58 months (18 to 155). Complications occurred in 39 patients (32%) at a mean of 11 months (0.5 to 39). The rate of nonunion was 7.4% (n = 9) and of avascular necrosis was 11.5% (n = 14). Failures were more common in patients over 40 years of age (p = 0.03). Univariate analysis identified that delay in time to fixation (>
24 hours), alcohol excess and pre-existing renal, liver or respiratory disease were all predictive of failure (all p <
0.05). Of these, alcohol excess, renal disease and respiratory disease were most predictive of failure on multivariate analysis. Younger patients with fractures of the femoral neck should be carefully evaluated for comorbidities that increase the risk of failure after reduction and fixation. In patients with a history of alcohol abuse, renal or respiratory disease, arthroplasty should be considered as an alternative treatment.
We report the outcome at a minimum of five years of 110 consecutive metal-on-metal Birmingham Hip Resurfacing arthroplasties in 98 patients. The procedures were performed between October 1999 and June 2002 by one surgeon. All patients were followed up clinically and radiologically. The mean follow-up was 71 months (60 to 93). Revision of either component was defined as failure. The mean Harris Hip score at follow-up was 96.4 (53 to 100). The mean Oxford hip score was 41.9 (16 to 57) pre-operatively and 15.4 (12 to 49) post-operatively (p <
0.001). The mean University of California Los Angeles activity score was 3.91 (1 to 10) pre-operatively and 7.5 (4 to 10) post-operatively (p <
0.001). There were four failures giving a survival at five years of 96.3% (95% confidence interval 92.8 to 99.8). When applying a new method to estimate narrowing of the femoral neck we identified a 10% thinning of the femoral neck in 16 hips (14.5%), but the relevance of this finding to the long-term outcome remains unclear. These good medium-term results from an independent centre confirm the original data from Birmingham.
The long-term effects of metal-on-metal arthroplasty are currently under scrutiny because of the potential biological effects of metal wear debris. This review summarises data describing the release, dissemination, uptake, biological activity, and potential toxicity of metal wear debris released from alloys currently used in modern orthopaedics. The introduction of risk assessment for the evaluation of metal alloys and their use in arthroplasty patients is discussed and this should include potential harmful effects on immunity, reproduction, the kidney, developmental toxicity, the nervous system and carcinogenesis.
