Aims. Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to
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
Tumour necrosis factor-α (TNF) is thought to play a role in aseptic loosening, the major cause of implant failure after total hip arthroplasty (THA). Natural sequence variations at –238 and –308 in the promoter region of the TNF gene are associated with differences in the susceptibility and severity of several TNF-mediated diseases. We tested whether carriage of the [less common] ‘A’ allele at –238 and –308 are associated with aseptic loosening after THA. 481 Caucasians (214 with failed implants versus 267 with radiologically intact implants) were recruited 11.7± 4.1 years after cemented THA for osteoarthritis. Genomic DNA was extracted from peripheral blood and genotyped for the –238 and –308 polymorphisms using the Taqman® 5′ nuclease method. 500 subjects from the local population were also genotyped using Taqman® to establish the background prevalence of the ‘A’ allele at each site. The carriage rate of –238A was 8.8% in the background population and 10.9% in the THA controls (P>
0.05). –238A carriage in the loosening group was 17.3% (odds ratio 1.72, 95% confidence interval 1.02 to 2.90). Carriage was highest (20.5%) in subjects with loosening of both the femoral and pelvic implant components (odds ratio 2.12; 1.17 to 3.83). The association of –238A with aseptic loosening was independent of age, sex, and amount of implant wear (Cox hazard ratio 1.49 (1.04 to 2.13; P=0.03)). Carriage of –308A was not associated with aseptic loosening. Genetic, as well as environmental factors, influence implant failure after THA. Whether the –238 polymorphism causes the biological change that predisposes to loosening, or is in linkage disequilibrium with such a locus, is not yet known.
Abstract. Introduction. Adverse reactions to pain medication and pain can delay discharge after outpatient knee arthroplasty (TKA). Pharmacogenomics is an emerging tool that might help reduce adverse events by tailoring medication use based on known
Objectives. Excessive acetabular coverage is the most common cause of pincer-type
femoroacetabular impingement. To date, an association between acetabular
over-coverage and
Introduction. Pharmacogenetics evaluates a patient's DNA to determine if a particular drug is expected to have a normal clinical effect, heightened effect, or no effect at all on a patient. It may also predict which patients are most likely to experience side effects from the medications. The purpose of this study was to use pharmacogenetic testing to determine how frequently total knee arthroplasty (TKA) patients have genetic variants to standard postoperative pain medications. We further sought to determine if changing the multimodal program based on these results would improve pain control and reduce side effects. Methods. In this prospective, randomized study, buccal cheek swab samples were collected from 31 primary TKA patients. Pharmacogenetics testing was performed on the samples to examine genetic variants in genes OPRM1, CYP1A2, CYP2B6, CYP2C19, CYP3A4, CYP2C9, and CYP2D6. These genes affect the pharmacodynamics and pharmacokinetics of NSAIDs and opioids. We examined the frequency of a genetic variant to one of the multimodal medications we prescribe including celecoxib, hydrocodone, and tramadol. Subjects included 9 men and 22 women. Patients were randomized to one of two groups: the control group received the standard postoperative pain regimen; the study group received a customized regimen based on the pharmacogenetic results. For the first 10 postoperative days patients recorded pain scores, amount of pain medication taken, and any side effects experienced. Results.
Technological advances and shorter rescue times have allowed early and effective resuscitation after trauma and brought attention to the host response to injury. Trauma patients are at risk of progressive organ dysfunction from what appears to be an uncontrolled immune response. The availability of improved techniques of molecular diagnosis has allowed investigation of the role of
Toll-like receptors (TLRs) are crucial components of the immune system that recognize microbial infection and trigger anti-microbial host defense responses. Gram positive bacteria are causative factors of bone infections, as they alter the balance of coordinated activities during bone remodeling, stimulating osteoclastogenesis. The aim of the study was to investigate whether
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
The February 2023 Research Roundup360 looks at: Clinical and epidemiological features of scaphoid fracture nonunion; Routine sterile glove and instrument change at the time of abdominal wound closure to prevent surgical site infection (ChEETAh); Characterization of genetic risk of end-stage knee osteoarthritis treated with total knee arthroplasty; Platelet-rich plasma or autologous blood injection for plantar fasciitis; Volume and outcomes of joint arthroplasty; The hazards of absolute belief in the p-value laid bare.
The Osteoprotegerin/RANK/RANKL system has been implicated in the biological cascade of events initiated by particulate wear debris and bacterial infection resulting in periprosthetic bone loss around loosened total hip arthroplasties (THA). Individual responses to such stimuli may be dictated by
Introduction. Adolescent idiopathic scoliosis (AIS) is the most common paediatric spinal deformity, affecting about 3% of school-aged children worldwide. This disorder occurs in otherwise healthy children who bear no obvious deficiencies in the components of the spinal column itself. The cause of AIS is poorly understood, as is implied by the name. Lesions of the bony composition of the vertebrae, the vertebral endplates, the paraspinous muscles, or the neurological system each have been proposed to explain disease pathogenesis. Progress has been hampered by the absence of an obvious AIS animal model. Consequently we have used genetic studies in human populations to identify factors underlying AIS susceptibility. The complex inheritance and population frequency of AIS suggest that many genetic factors are involved in this disease. To search comprehensively for such factors we previously undertook the first genome-wide association study (GWAS) of AIS susceptibility in a cohort of 419 families in Texas, USA. We found that chromosome 3 SNPs in the proximity of the CHL1 gene yielded strongest results, which we replicated in additional cohorts (rs10510181 OR 1·49, 95% CI 1·29–173, p=2·58×10–8). CHL1 is of interest because it encodes an axon guidance protein and is functionally related to the ROBO3 gene that causes hereditary gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Here we expanded the study to 702 Texas families. Methods. We tested more than 327 000 single-nucleotide polymorphisms (SNPs) across all human autosomes for association with disease. Results. Results of the study in 702 Texas families yielded evidence for association with SNPs in a second axon guidance gene, DSCAM, which encodes a protein in the same structural and functional class with Chl1 and Robo3 (rs2222973 combined OR 0·59, 95% CI 0·48–0·74; p=1·46×10–6). We additionally found AIS associations with loci in CNTNAP2, whose protein product interacts directly with L1 and Robo class proteins and participates in axon pathfinding. Conclusions. These data support
Introduction: Modic changes are vertebral endplate changes visible in magnetic resonance imaging (MRI), which associate with degenerative intervertebral disc disease. Twin studies suggest that intervertebral disc degeneration and low back pain may be primarily explained by genetic factors. There are, however, no studies on genetic factors in Modic changes. Materials and methods: Eleven variations in eight genes (COL9A2, COL9A3, COL11A2, IL1A, IL1B, IL6, MMP-3 and VDR) were genotyped in an occupational cohort of 159 male train engineers and 69 male paper mill workers. All the study subjects were MRI scanned and evaluated for Modic changes. Results: Out of 228 subjects studied, 128 (56%) were found to have Modic change at one or more disc levels. 15% of them had exclusively Modic type I while 32% had exclusively Modic II changes. 10% of the subjects had both type I and type II changes. When single nucleotide polymorphisms (SNPs) were analyzed independently, none of them significantly associated with Modic changes. However, when the gene-gene interactions were evaluated IL1A and MMP-3 polymorphisms together associated with type II Modic changes (OR 3.2, 95% CI 1.2–8.5; p = 0.038). Furthermore, IL-1 gene cluster together with MMP-3 polymorphism associated significantly with type II Modic changes (OR = 8.14, 95% CI 1.72–38.44; p = 0.008). Discussion: This is the first study evaluating the role of genetic factors in relation to Modic changes.
Introduction. Idiopathic scoliosis (IS) has been associated with several genetic loci in varying study populations, reflecting the disorder's genetic complexity. One region of interest is on chromosome 17, flanking regions linked to neurofibromatosis type 1 (NF1). This region is of particular relevance because the most common osseous manifestation in NF1 is scoliosis (10–30% of patients). This alludes to a potential genetic correlation within this region affecting spinal development or stability. The objective of this research is to identify candidate genes within this region that are statistically linked to IS. Methods. An initial population of IS families recruited through approval by the institutional review board (202 families; 1198 individuals) had DNA harvested from blood, and underwent genomic screening, finemapping, and statistical analyses. We identified a specific familial subset: families with males having undergone surgery for scoliosis (17 families, 147 individuals). The initial genome-wide scan indicated that this subset was linked to chromosome 17q.11.2. The most prominent marker, D17s975, (p=0·0003) at 25.12 Mb is adjacent to the NF1 deletional region. We then analysed a custom panel of single-nucleotide polymorphisms (SNPs) extending from 18·30–31·47 Mb for linkage through Taqman SNP assay protocol. With allele specific fluorescent tags, allelic discrimination was done with real-time PCR. Results. Findings show two regions with two or more contiguous SNPs of significance (p<0·05), confirming significant linkage adjacent to the NF1 locus (table). The most significant results lie within the serotonin transporter gene SLC6A4, whose product is a modulator of serotonin (5-HT) activity. Conclusions. IS is a disorder of variable phenotypic expression that has been related to several regions on the genome. Although NF1 has been definitively associated with a region on chromosome 17, the phenotypic expression is not understood at the molecular level. The elucidation of shared
Aims: Tumour necrosis factor-alpha is a proinflammatory cytokine that has been implicated in the inflammatory response to bacterial infection and wear debris particles around loosened total hip replacements (THR). Individual TNF responses to such stimuli may be dictated by
Adolescent idiopathic scoliosis (AIS), defined by an age at presentation of 11 to 18 years, has a prevalence of 0.47% and accounts for approximately 90% of all cases of idiopathic scoliosis. Despite decades of research, the exact aetiology of AIS remains unknown. It is becoming evident that it is the result of a complex interplay of genetic, internal, and environmental factors. It has been hypothesized that genetic variants act as the initial trigger that allow epigenetic factors to propagate AIS, which could also explain the wide phenotypic variation in the presentation of the disorder. A better understanding of the underlying aetiological mechanisms could help to establish the diagnosis earlier and allow a more accurate prediction of deformity progression. This, in turn, would prompt imaging and therapeutic intervention at the appropriate time, thereby achieving the best clinical outcome for this group of patients. Cite this article:
Aseptic loosening arises when periprosthetic bone loss results in mechanical failure at the host-implant interface, and is the main factor limiting implant survival after total hip arthroplasty (THA). The aims of this study were to determine whether
Our knowledge of the incidence of scoliosis and scoliosis surgery is based on a few small scale studies. The National Health Service (NHS) in the United Kingdom has long collected data on hospital based activity. We have used a five year English database (1998–2002) of hospital admission statistics to study age-adjusted admission rates for scoliosis (code M41 in the International Classification of Diseases, 10th revision) and for two scoliosis surgery codes (V41 ‘instrumental correction of deformity of spine’ and V42 ‘other correction of deformity of spine’ (the latter includes ‘anterolateral release of spine for correction of deformity’). Results: Three thousand, seven hundred and eighty three patients (2533 females and 1240 males) aged 5–29 years had diagnosis M41 recorded over the five year sample period. Most of the patients were teenagers. 971 (males and females) of these had operation V41 and 1212 had V42, it is likely that the vast majority of these cases had idiopathic scoliosis. We made regional maps based on age-adjusted admission rates/100000 population. Admission rates varied from 5.75/100000 (95% confidence intervals x to y) in London to 2.8/100000 (x to y) in the Yorkshire-Humberside region. Interpretation: There was wide geographical variation in admission rates. We considered 5 hypotheses:. Social deprivation – we were able to study this, and admission rates appeared independent of social deprivation. Availability of spine surgeons – this may be an explanation, but not very convincing. Scoliosis surgery is concentrated in 15 centres that do not obviously link with the variations we found. Variation in decision making about referral and/or treatment (by general practitioners, patients or surgeons). This is possible, but cannot be studied using our data. Regional
The purpose of this study is to determine an individual’s age-specific prevalence of total knee arthroplasty (TKA) after cruciate ligament surgery, and to identify clinical and genetic risk factors associated with undergoing TKA. This study was a retrospective case-control study using the UK Biobank to identify individuals reporting a history of cruciate ligament surgery. Data from verbal history and procedural codes recorded through the NHS were used to identify instances of TKA. Patient clinical and genetic data were used to identify risk factors for progression from cruciate ligament surgery to TKA. Individuals without a history of cruciate ligament reconstruction were used for comparison.Aims
Methods
Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA. We used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs.Aims
Methods