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1.
Knee ; 48: 94-104, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38565038

RESUMO

BACKGROUND: The aims were to assess whether a specific subgroup(s) of patients had a clinically significant benefit in their knee specific outcome or health-related quality of life (HRQoL) when undergoing robotic total knee arthroplasty (rTKA) when compared to manually performed TKA (mTKA). METHODS: One hundred patients were randomised to either rTKA or mTKA, 50 to each group, of which 46 and 41 were available for functional review at 6-months, respectively. Subgroup analysis was undertaken for sex, age (<67-years versus ≥ 67-years), preoperative WOMAC score (<40 versus ≥ 40) and EQ-5D utility (<0.604 versus ≥ 0.604). RESULTS: Male patients undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (mean difference (MD) 16.3, p = 0.011) at 2-months, function (MD 12.6, p = 0.032) and total score (MD 12.7, p = 0.030), and OKS (MD 6.0, p = 0.030) at 6-months. Patients < 67-years old undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (MD 10.3, p = 0.039) at 2-months, and function (MD 12.9, p = 0.040) and total (MD 13.1, p = 0.038) scores at 6-months. Patients with a preoperative WOMAC total score of < 40 points undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (MD 14.6, p = 0.044) at 6-months. Patients with a preoperative EQ-5D utility of <0.604 undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (MD 15.5, p = 0.011) at 2-months. CONCLUSION: Patients of male sex, younger age, worse preoperative knee specific function and HRQoL had a clinically significantly better early functional outcome with rTKA when compared to mTKA.

2.
Arthritis Res Ther ; 26(1): 78, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570801

RESUMO

BACKGROUND: Transitioning from a genetic association signal to an effector gene and a targetable molecular mechanism requires the application of functional fine-mapping tools such as reporter assays and genome editing. In this report, we undertook such studies on the osteoarthritis (OA) risk that is marked by single nucleotide polymorphism (SNP) rs34195470 (A > G). The OA risk-conferring G allele of this SNP associates with increased DNA methylation (DNAm) at two CpG dinucleotides within WWP2. This gene encodes a ubiquitin ligase and is the host gene of microRNA-140 (miR-140). WWP2 and miR-140 are both regulators of TGFß signaling. METHODS: Nucleic acids were extracted from adult OA (arthroplasty) and foetal cartilage. Samples were genotyped and DNAm quantified by pyrosequencing at the two CpGs plus 14 flanking CpGs. CpGs were tested for transcriptional regulatory effects using a chondrocyte cell line and reporter gene assay. DNAm was altered using epigenetic editing, with the impact on gene expression determined using RT-qPCR. In silico analysis complemented laboratory experiments. RESULTS: rs34195470 genotype associates with differential methylation at 14 of the 16 CpGs in OA cartilage, forming a methylation quantitative trait locus (mQTL). The mQTL is less pronounced in foetal cartilage (5/16 CpGs). The reporter assay revealed that the CpGs reside within a transcriptional regulator. Epigenetic editing to increase their DNAm resulted in altered expression of the full-length and N-terminal transcript isoforms of WWP2. No changes in expression were observed for the C-terminal isoform of WWP2 or for miR-140. CONCLUSIONS: As far as we are aware, this is the first experimental demonstration of an OA association signal targeting specific transcript isoforms of a gene. The WWP2 isoforms encode proteins with varying substrate specificities for the components of the TGFß signaling pathway. Future analysis should focus on the substrates regulated by the two WWP2 isoforms that are the targets of this genetic risk.


Assuntos
MicroRNAs , Osteoartrite , Adulto , Humanos , Sequência de Bases , Ubiquitina/genética , Ubiquitina/metabolismo , Isoformas de Proteínas/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Metilação de DNA/genética , MicroRNAs/metabolismo , Osteoartrite/genética , Osteoartrite/metabolismo , Fator de Crescimento Transformador beta/metabolismo
3.
Arch Orthop Trauma Surg ; 144(1): 23-30, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37561165

RESUMO

INTRODUCTION: Unicompartmental knee replacement (UKR) is an effective surgical strategy in patients with isolated medial or lateral compartment osteoarthritis. Study aims were to (1) describe the epidemiology of patients undergoing revision of UKR to a hinge knee replacement (HKR); (2) identify factors influencing time to revision; (3) evaluate HKR survival. MATERIALS AND METHODS: An analysis of National Joint Registry data was undertaken, exploring revision of UKR to HKR between 2007 and April 2021. Descriptive analysis of eligible patients and Cox Regression to identify key determinants of time to revision were performed. Failure of HKR post-revision was assessed using survival analysis. RESULTS: 111 patients underwent revision of UKR to HKR. Median age at revision was 70 years and most common indications were instability (n = 42) and infection (n = 22). The most common implant was a rotating HKR. Significant independent factors associated with earlier revision were periprosthetic fracture (p = 0.03) and malalignment (p = 0.03). Progressive osteoarthritis (p = 0.01) and higher ASA grades (3: p = 0.01, 4: p < 0.01) delayed time to revision; patient sex and age were not significant factors. Ten patients required subsequent re-revision; median age at re-revision was 61 years. HKR revised from UKR had an 89.3% revision-free risk at 5 years. Male sex (p < 0.01) and younger age (p < 0.01) were associated with re-revision. CONCLUSIONS: Factors associated with time to revision may be used to counsel patients prior to UKR. The survivorship of the HKR of 89.3% at 5 years is concerning and careful consideration should be given when using this level of constraint when revising UKR in younger or male patients.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Masculino , Pessoa de Meia-Idade , Inglaterra/epidemiologia , Irlanda do Norte/epidemiologia , Osteoartrite do Joelho/cirurgia , Falha de Prótese , Sistema de Registros , Reoperação , Resultado do Tratamento , País de Gales/epidemiologia , Feminino
4.
Bone Jt Open ; 4(9): 720-727, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37730212

RESUMO

Aims: Achievement of accurate microbiological diagnosis prior to revision is key to reducing the high rates of persistent infection after revision knee surgery. The effect of change in the microorganism between the first- and second-stage revision of total knee arthroplasty for periprosthetic joint infection (PJI) on the success of management is not clear. Methods: A two-centre retrospective cohort study was conducted to review the outcome of patients who have undergone two-stage revision for treatment of knee arthroplasty PJI, focusing specifically on isolated micro-organisms at both the first- and second-stage procedure. Patient demographics, medical, and orthopaedic history data, including postoperative outcomes and subsequent treatment, were obtained from the electronic records and medical notes. Results: The study cohort consisted of 84 patients, of whom 59.5% (n = 50) had successful eradication of their infection at a mean follow-up of 4.7 years. For the 34 patients who had recurrence of infection, 58.8% (n = 20) had a change in isolated organism, compared to 18% (n = 9) in the infection eradication group (p < 0.001). When adjusting for confound, there was no association when the growth on the second stage was the same as the first (odd ratio (OR) 2.50, 95% confidence interval (CI) 0.49 to 12.50; p = 0.269); however, when a different organism was identified at the second stage, this was independently associated with failure of treatment (OR 8.40, 95% CI 2.91 to 24.39; p < 0.001). There were no other significant differences between the two cohorts with regard to patient demographics or type of organisms isolated. Conclusion: Change in the identified microorganism between first- and second-stage revision for PJI was associated with failure of management. Identification of this change in the microorganism prior to commencement of the second stage may help target antibiotic management and could improve the success of surgery in these patients.

5.
Bone Joint J ; 105-B(10): 1132, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37777194
6.
Bone Joint J ; 105-B(9): 961-970, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37652449

RESUMO

Aims: The primary aim was to assess whether robotic total knee arthroplasty (rTKA) had a greater early knee-specific outcome when compared to manual TKA (mTKA). Secondary aims were to assess whether rTKA was associated with improved expectation fulfilment, health-related quality of life (HRQoL), and patient satisfaction when compared to mTKA. Methods: A randomized controlled trial was undertaken, and patients were randomized to either mTKA or rTKA. The primary objective was functional improvement at six months. Overall, 100 patients were randomized, 50 to each group, of whom 46 rTKA and 41 mTKA patients were available for review at six months following surgery. There were no differences between the two groups. Results: There was no difference between rTKA and mTKA groups at six months according to the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) functional score (mean difference (MD) 3.8 (95% confidence interval (CI) -5.6 to 13.1); p = 0.425). There was a greater improvement in the WOMAC pain score at two months (MD 9.5 (95% CI 0.6 to 18.3); p = 0.037) in the rTKA group, although by six months no significant difference was observed (MD 6.7 (95% CI -3.6 to 17.1); p = 0.198). The rTKA group were more likely to achieve a minimal important change in their WOMAC pain score when compared to the mTKA group at two months (n = 36 (78.3%) vs n = 24 (58.5%); p = 0.047) and at six months (n = 40 (87.0%) vs n = 29 (68.3%); p = 0.036). There was no difference in satisfaction between the rTKA group (97.8%; n = 45/46) and the mTKA group (87.8%; n = 36/41) at six months (p = 0.096). There were no differences in EuroQol five-dimension questionnaire (EQ-5D) utility gain (p ≥ 0.389) or fulfilment of patient expectation (p ≥ 0.054) between the groups. Conclusion: There were no statistically significant or clinically meaningful differences in the change in WOMAC function between mTKA and rTKA at six months. rTKA was associated with a higher likelihood of achieving a clinically important change in knee pain at two and six months, but no differences in knee-specific function, patient satisfaction, health-related quality of life, or expectation fulfilment were observed.


Assuntos
Artroplastia do Joelho , Procedimentos Cirúrgicos Robóticos , Humanos , Qualidade de Vida , Articulação do Joelho/cirurgia , Dor
7.
Arch Bone Jt Surg ; 11(4): 278-284, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37180287

RESUMO

Objectives: The primary aim was to assess the association between bone resection and the resultant flexion and extension gaps in the medial and lateral compartments of the knee when performing robotic-arm assisted total knee arthroplasty (rTKA). The secondary aims were to compare medial and lateral bone resections and the influence on limb alignment, and whether the amount of bone resection that resulted in equal gaps was predictable. Methods: A prospective study of 22 consecutive patients with a mean age of 66 years undergoing rTKA was conducted. The femoral component was mechanically aligned, and the alignment of the tibial component was adjusted (+/-3degrees of the mechanical axis) to obtain equal extension and flexion gaps. All knees underwent soft tissue balancing using sensor-guided technology. The final compartmental bone resection, gaps, and implant alignment were obtained from the robot data archive. Results: There was a correlation between bone resection and the resultant gap in the medial (r=0.433, p=0.044) and lateral (r=0.724, p<0.001) compartments of the knee. There were no differences in bone resection from the distal femur and posterior condyles in the medial (p=0.941) or lateral compartments (p=0.604) or for the resultant gaps (p=0.341 and p=0.542, respectively). There was more bone removed from the medial compartment compared to the lateral aspect: 0.9mm (p=0.005) in extension and 1.2mm (p=0.026) flexion. The differential bone resection changed the knee alignment by one degree of varus. There were no significant differences between the actual and predicted medial (difference 0.05, p=0.893) or lateral (difference 0.00, p=0.992) tibial bone resection. Conclusion: There was a direct association between bone resection and resultant compartment joint gap when using rTKA, which was predictable. Gap balancing was achieved when less bone was resected from the lateral compartment which resulted in an estimated one-degree varus alignment of the knee.

8.
Postgrad Med J ; 99(1169): 127-138, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37222068

RESUMO

Self-reported questionnaires have become a widely adopted method of reviewing patients in clinical practice. This systematic review aimed to determine the reliability of patient-reported comorbidities and to identify which patient factors influence the reliability. Included studies assessed the reliability of at least one patient-reported comorbidity against their medical record or clinical assessment as gold standard. Twenty-four eligible studies were included in the meta-analysis. Only endocrine diseases (Cohen's Kappa Coefficient (CKC) 0.81 (95% CI 0.76 to 0.85)), consisting of diabetes mellitus (CKC 0.83 (95% CI 0.80 to 0.86)) and thyroid disease (CKC 0.68 (95% CI 0.50 to 0.86)), showed good-to-excellent reliability. Factors most frequently reported to influence concordance included age, sex and educational level. This systematic review demonstrated poor-to-moderate reliability for most systems, except for endocrine which showed good-to-excellent reliability. Although patient self-reporting can be a useful guide to clinical management, several patient factors were demonstrated to affect reliability therefore it should be avoided as a standalone measure.


Assuntos
Registros Médicos , Medidas de Resultados Relatados pelo Paciente , Humanos , Reprodutibilidade dos Testes , Comorbidade , Escolaridade
9.
Bone Joint J ; 105-B(1): 47-55, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36587261

RESUMO

AIMS: The aim of this study was to identify variables associated with time to revision, demographic details associated with revision indication, and type of prosthesis employed, and to describe the survival of hinge knee arthroplasty (HKA) when used for first-time knee revision surgery and factors that were associated with re-revision. METHODS: Patient demographic details, BMI, American Society of Anesthesiologists (ASA) grade, indication for revision, surgical approach, surgeon grade, implant type (fixed and rotating), time of revision from primary implantation, and re-revision if undertaken were obtained from the National Joint Registry data for England, Wales, Northern Ireland, and the Isle of Man over an 18-year period (2003 to 2021). RESULTS: There were 3,855 patient episodes analyzed with a median age of 73 years (interquartile range (IQR) 66 to 80), and the majority were female (n = 2,480, 64.3%). The median time to revision from primary knee arthroplasty was 1,219 days (IQR 579 to 2,422). Younger age (p < 0.001), decreasing ASA grade (p < 0.001), and indications for revision of sepsis (p < 0.001), unexplained pain (p < 0.001), non-polyethylene wear (p < 0.001), and malalignment (p < 0.001) were all associated with an earlier time to revision from primary implantation. The median follow-up was 4.56 years (range 0.00 to 17.52), during which there were 410 re-revisions. The overall unadjusted probability of re-revision for all revision HKAs at one, five, and ten years after surgery were 2.7% (95% confidence interval (CI) 2.2 to 3.3), 10.7% (95% CI 9.6 to 11.9), and 16.2% (95% CI 14.5 to 17.9), respectively. Male sex (p < 0.001), younger age (p < 0.001), revision for septic indications (p < 0.001) or implant fracture (p = 0.010), a fixed hinge (p < 0.001), or surgery performed by a non-consultant grade (p = 0.023) were independently associated with an increased risk of re-revision. CONCLUSION: There were several factors associated with time to first revision. The re-revision rate was 16.2% at ten years; however, the risk factors associated with an increased risk of re-revision could be used to counsel patients regarding their outcome.Cite this article: Bone Joint J 2023;105-B(1):47-55.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Humanos , Masculino , Feminino , Idoso , Artroplastia do Joelho/efeitos adversos , Desenho de Prótese , Prótese do Joelho/efeitos adversos , Fatores de Risco , Reoperação , Sistema de Registros , Falha de Prótese
10.
Bone Jt Open ; 3(9): 692-700, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36053188

RESUMO

AIMS: The primary aim of our study was to assess the influence of age on hip-specific outcome following total hip arthroplasty (THA). Secondary aims were to assess health-related quality of life (HRQoL) and level of activity according to age. METHODS: A prospective cohort study was conducted. All patients were fitted with an Exeter stem with a 32 mm head on highly cross-linked polyethylene (X3RimFit) cemented acetabulum. Patients were recruited into three age groups: < 65 years, 65 to 74 years, and ≥ 75 years, and assessed preoperatively and at three, 12, 24, and 60 months postoperatively. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and Hip disability and Osteoarthritis Outcome Score (HOOS), were used to assess hip-specific outcome. EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and 36-Item Short Form Survey (SF-36) scores were used to assess HRQoL. The Lower Extremity Activity Scale (LEAS) and Timed Up and Go (TUG) were used to assess level of activity. RESULTS: There were no significant (p > 0.05) differences in the WOMAC scores, HSS, HOOS, or EQ-5D-5L at any postoperative timepoint between the age groups. Patients aged ≥ 75 years had significantly lower physical function (p ≤ 0.010) and physical role (p ≤ 0.047) SF-36 scores at 12, 24, and 60 months, but were equal to that expect of an age-matched population. No differences according to age were observed for the other six domains of the SF-36 (p > 0.060). The ≥ 75 years group had a lower LEAS (p < 0.001) and longer TUG test times (p ≤ 0.032) compared to the < 65 years group, but older age groups had significant (p < 0.001) improvement relative to their preoperative baseline measures. CONCLUSION: Age did not influence postoperative hip-specific outcome or HRQoL (according to the EQ-5D) following THA. Despite a significant improvement, older patients had lower postoperative activity levels compared to younger patients, but this may be reflective of the overall physical effect of ageing.Cite this article: Bone Jt Open 2022;3(9):692-700.

11.
Arthritis Res Ther ; 24(1): 189, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941660

RESUMO

BACKGROUND: Osteoarthritis is highly heritable and genome-wide studies have identified single nucleotide polymorphisms (SNPs) associated with the disease. One such locus is marked by SNP rs11732213 (T > C). Genotype at rs11732213 correlates with the methylation levels of nearby CpG dinucleotides (CpGs), forming a methylation quantitative trait locus (mQTL). This study investigated the regulatory activity of the CpGs to identify a target gene of the locus. METHODS: Nucleic acids were extracted from the articular cartilage of osteoarthritis patients. Samples were genotyped, and DNA methylation was quantified by pyrosequencing at 14 CpGs within a 259-bp interval. CpGs were tested for enhancer effects in immortalised chondrocytes using a reporter gene assay. DNA methylation at the locus was altered using targeted epigenome editing, with the impact on gene expression determined using quantitative polymerase chain reaction. RESULTS: rs11732213 genotype correlated with DNA methylation at nine CpGs, which formed a differentially methylated region (DMR), with the osteoarthritis risk allele T corresponding to reduced levels of methylation. The DMR acted as an enhancer and demethylation of the CpGs altered expression of TMEM129. Allelic imbalance in TMEM129 expression was identified in cartilage, with under-expression of the risk allele. CONCLUSIONS: TMEM129 is a target of osteoarthritis genetic risk at this locus. Genotype at rs11732213 impacts DNA methylation at the enhancer, which, in turn, modulates TMEM129 expression. TMEM129 encodes an enzyme involved in protein degradation within the endoplasmic reticulum, a process previously implicated in osteoarthritis. TMEM129 is a compelling osteoarthritis susceptibility target.


Assuntos
Osteoartrite , Ubiquitina-Proteína Ligases/genética , Ilhas de CpG , Metilação de DNA/genética , Humanos , Osteoartrite/genética , Osteoartrite/metabolismo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Ubiquitina-Proteína Ligases/metabolismo
12.
J Biomed Mater Res B Appl Biomater ; 110(10): 2290-2298, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35657060

RESUMO

Flanged acetabular cups were developed with the rationale that, at insertion, they would increase the pressure of the cement and improve penetration of cement into the acetabular bone. Various studies have been inconclusive regarding their effectiveness. In this work, we aimed to eliminate all confounding factors and measure the pressures generated during acetabular pressurization and cup implantation using a simplified steel acetabulum, high precision pressure transducers, proper surgical techniques and two acetabular cups, identical apart from the addition of a flange to one. It was found that the flanged acetabular component did not significantly increase the pressure in the acetabulum and in some cases reduced the pressures generated when compared to an unflanged cup. The addition of a flange did not reduce the pressure differential between the pole and the rim of the acetabulum, nor did it have a significant effect on pressure lost over the cup implantation period. It was concluded that flanged acetabular cups provide no significant improvement in the pressures generated in the acetabulum during acetabular cup implantation. It is hypothesized that the flange may be seen as a design feature intended to slow the insertion of the cup into the cement, thus requiring the surgeon to apply a larger load in order to correctly position the acetabular cup; in this way larger pressure will be generated.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Cimentos Ósseos , Pressão , Desenho de Prótese
13.
Knee ; 34: 279-287, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35101741

RESUMO

BACKGROUND: The aim was to describe temporal changes and associated changes in patient demographics and surgical variables, revision rate and factors associated with revision of primary hinge knee arthroplasty (HKA) in the UK. METHODS: National Joint Registry data for England, Wales, Northern Ireland and Isle of Mann was used to examine the temporal trends in patient demographics, surgical factors and indications for primary HKA usage over a 16-year (2003 to 2018) period and associated risk factors for revision. RESULTS: There were 4921 patient episodes with a median follow up of 5.5 (range 0 to 16.3) years. The median age was 75years and the majority were female (72.9%). There was a tenfold increase in the use of HKA (p < 0.001), with an increased relative usage in female patients (p = 0.010), but no significant changes in age (p = 0.484) or BMI (p = 0.781). There were 227 revisions performed at a median of 695days. The overall unadjusted probabilities of revision at 1, 5 and 10 years were 1.5% (95% confidence intervals (CI) 1.1to1.8), 4.4% (95%CI 3.7 to 5.0) and 6.4% (95%CI 5.5 to 7.3), respectively. Cox proportional hazard analysis demonstrated younger age (p < 0.01), male sex (hazard ratio (HR) 1.43, p < 0.01), morbid obesity (HR 2.31, p = 0.022) or previous trauma as the indication (HR 1.48, p = 0.025) were associated with an increased risk of revision. CONCLUSION: There was an increase in the use of HKA with increased uptake among female patients. The revision rate was a 6.4% at 10 years, however, younger age, male sex, morbid obesity or previous trauma were associated with an increased risk of revision. LEVEL OF EVIDENCE: III Retrospective study.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Idoso , Feminino , Humanos , Masculino , Desenho de Prótese , Falha de Prótese , Sistema de Registros , Reoperação , Estudos Retrospectivos , Fatores de Risco
14.
Bone ; 158: 116371, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35192969

RESUMO

Osteoporosis is a skeletal disease which is characterised by reduced bone mass and microarchitecture, with a subsequent loss of strength that predisposes to fragility and risk of fractures. The pathogenesis of falling bone mineral density, ultimately leading to a diagnosis of osteoporosis is incompletely understood but the disease is currently thought to be multifactorial. Humans are known to accumulate mitochondrial mutations and respiratory chain deficiency with age and mounting evidence suggests that this may indeed be the overarching cause intrinsic to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of about 30 years onwards. Mitochondria contain their own genome which encodes 13 essential mitochondrial proteins and accumulates somatic variants at up to 10 times the rate of the nuclear genome. Once the concentration of any pathogenic mitochondrial genome variant exceeds a threshold, respiratory chain deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model is a knock-in mutant that expresses a proof-reading-deficient version of PolgA, a nuclear encoded subunit of mtDNA polymerase. These mice are a useful model of age-related accumulation of mtDNA mutations in humans since their defective proof-reading mechanism leads to a mitochondrial DNA mutation rate 3-5 times higher than in wild-type mice. These mice showed enhanced levels of age-related osteoporosis along with respiratory chain deficiency in osteoblasts. To explore whether respiratory chain deficiency is also seen in human osteoblasts, we developed a protocol and analysis framework for imaging mass cytometry in bone tissue sections to analyse osteoblasts in situ. By comparing bone tissue sampled at one timepoint from femoral neck of 10 older healthy volunteers aged 40-85 with samples from young patients aged 1-19, we have identified complex I defect in osteoblasts from 6 out of 10 older volunteers, complex II defect in 2 out of 10 older volunteers, complex IV defect in 1 out of 10 older volunteers and complex V defect in 4 out of 10 older volunteers. These observations are consistent with findings from the PolgD257A/D257A mouse model and suggest that respiratory chain deficiency, as a consequence of the accumulation of age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis.


Assuntos
DNA Mitocondrial , Mitocôndrias , Animais , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Transporte de Elétrons , Humanos , Citometria por Imagem , Camundongos , Mitocôndrias/metabolismo , Mutação/genética , Osteoblastos/metabolismo
15.
Trials ; 23(1): 70, 2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35065657

RESUMO

BACKGROUND: Robotic-arm-assisted knee arthroplasty allows for more accurate component positioning and alignment and is associated with better patient-reported outcomes compared to manually performed jig-based knee arthroplasty. However, what is not known is whether the addition of an intra-articular sensor (VerasenseTM) to aid intraoperative balancing of the total knee replacement (TKR) offers improved functional outcomes for the patient. The purpose of this research is to compare the outcomes of patients undergoing a conventional manual knee replacement to those undergoing TKR using robotic-assisted surgery and the VerasenseTM to optimise alignment and balance the knee joint, respectively, and assess the associated cost economics of such technology. METHODS AND ANALYSIS: This randomised controlled trial will include 90 patients with end-stage osteoarthritis of the knee undergoing primary TKR. Patients meeting the inclusion/exclusion criteria that consent to be in the study will be randomised at a ratio of 1:1 to either manual TKR (standard of care) or robotic-arm-assisted TKR with VerasenseTM to aid balancing of the knee. The primary objective will be functional improvement at 6 months following surgery between the two groups. The secondary objectives are to compare changes in knee-specific function, joint awareness, patient expectation and fulfilment, satisfaction, pain, stiffness and functional ability, health-related quality of life, cost-effectiveness, and gait patterns between the two groups. Ethical approval was obtained by the Tyne & Wear South Research Ethics Committee, UK. The study is sponsored by the Newcastle Hospitals NHS Foundation Trust. DISCUSSION: This study will assess whether the improved accuracy of component positioning using the robotic-arm-assisted surgery and the VerasenseTM to aid balancing of the TKR offers improved outcome relative to standard manual jig-based systems that are currently the standard of care. This will be assessed primarily according to knee-specific function, but several other measures will also be assessed including whether these are cost-effective interventions. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN47889316 https://doi.org/10.1186/ISRCTN47889316 . Registered on 25 November 2019 DATE AND VERSION FOR PROTOCOL: ROAM Protocol V1.0 (13-12-2018).


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Procedimentos Cirúrgicos Robóticos , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
16.
J Knee Surg ; 35(6): 684-691, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-32942332

RESUMO

The aim of this study was to assess whether depression had a clinically significant influence on the functional improvement of total knee arthroplasty (TKA) according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and whether it influences patient satisfaction at 1 year. A retrospective cohort of 3,510 primary TKA was identified from an arthroplasty database. Patient demographics, comorbidities, WOMAC, and Short Form-12 (SF-12) scores were collected preoperatively and 1 year postoperatively. Patient satisfaction (overall, pain relief, return to work, and recreational activity) was assessed at 1 year. There were 444 (12.6%) patients who self-reported depression. Patients with depression were younger (p < 0.001), had a higher body mass index (BMI; p < 0.001), were more likely to be female (p < 0.001), had lung (p < 0.001), neurological (p = 0.018), kidney (p = 0.001), liver (p < 0.001), and gastric (p < 0.001) disease, report associated diabetes (p = 0.001), and back pain (p < 0.001) relative to the subgroup without depression. All preoperative WOMAC functional measures were significantly (p < 0.001) worse in patients with reported depression. When adjusting for these confounding differences, patients with depression had a clinically equal improvement in their WOMAC scores at 1 year compared to those patients without. Depression was not associated with a clinically significant difference in improvement of knee-specific outcome (WOMAC) but was independently associated with a lower rate of patient satisfaction 1 year after TKA. Patients with depression were approximately twice as likely to be dissatisfied at 1 year when compared with those without depression. This is a prognostic retrospective cohort study and reflects level of evidence III.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Depressão , Feminino , Humanos , Masculino , Osteoartrite do Joelho/cirurgia , Satisfação do Paciente , Satisfação Pessoal , Estudos Retrospectivos , Resultado do Tratamento
17.
Acta Orthop Belg ; 87(3): 563-569, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34808734

RESUMO

The primary aim of this study was to assess the utility of the alpha defensin lateral flow (ADLF) test for predicting the eradication of PJI after surgical debridement. The secondary aim was to describe the reliability of ADLF test in diagnosis of PJI intra- operatively. A prospective observational study was conducted in three independent orthopaedic centres. Twenty-two patients undergoing revision surgery (debridement, antibiotics and implant retention (DAIR), single or two-stage revision) for PJI were recruited, 13 female and 9 male with an average age of 64 years. Samples were collected intra-operatively at the start of the first surgical procedure and then at the completion of debridement or prior to reimplantation depending on the operation performed. These samples were tested using ADLF and then sent for microbiological analysis. The ADLF result was then compared to the corresponding culture result in order to determine the diagnostic predictive accuracy. The reliability of ADLF test to predict eradication of infection after debridement of PJI was excellent for specificity and positive predictive value (PPV) of which both where 100%, but had a poor sensitivity (14.3%) and negative predictive value (NPV) (62.5%). The reliability of ADLF test to predict PJI was poor with only a 50% sensitivity and specificity. The ADLF test has a high specificity and PPV for diagnosing eradication of infection after debridement. In contrast the ADLF testing appears to have poor diagnostic accuracy for PJI when used on intra-operative samples, prior to surgical intervention.


Assuntos
Artroplastia de Quadril , Infecções Relacionadas à Prótese , alfa-Defensinas , Antibacterianos/uso terapêutico , Desbridamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/cirurgia , Reprodutibilidade dos Testes , Estudos Retrospectivos
18.
Acta Orthop Belg ; 87(2): 374-381, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34529395

RESUMO

The primary aim of this study was to assess the diagnostic accuracy of joint aspiration culture, serum C-reactive protein (CRP) and serum erythrocyte sedimentation rate (ESR), individually, and in combination for the diagnosis of periprosthetic joint infection (PJI). A consecutive patient series with pre-operative inflammatory marker levels, an aspiration culture of either hip or knee arthroplasty and intra-operative culture samples from subsequent revision surgery was compiled. This retrospective patient cohort analysis included 128 aspiration. The data were analysed to compare pre-operative aspiration cultures, serum ESR and CRP levels to the chosen gold standard for PJI diagnosis of intra-operative culture samples. A diagnostic algorithm was created using the above tests combined with clinical suspicion index. The values that had the highest sensitivity and specificity of predicting PJI were >5 for CRP and >16 for ESR. CRP used individually had the highest sensitivity and negative predictive value (NPV) of any test (75.0% and 75.9%, respectively). ESR + aspirate had the highest specificity and positive predictive value (PPV), of 100% for both. Using all three tests together the specificity and PPV were higher than the test individual values (95.3% and 85.0% respectively). Based on subgroup analyses the combination of ESR or CRP plus joint aspiration has superior PPV compared to individual tests. ESR and CRP had the highest NPV when used in isolation. An algorithm has been developed to guide clinical diagnosis.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Infecções Relacionadas à Prótese , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Biomarcadores , Sedimentação Sanguínea , Proteína C-Reativa , Humanos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/cirurgia , Estudos Retrospectivos , Sensibilidade e Especificidade
20.
Bone Joint J ; 103-B(4): 672-680, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33752468

RESUMO

AIMS: The aim of this study was to assess the quality of life of patients on the waiting list for a total hip (THA) or knee arthroplasty (KA) during the COVID-19 pandemic. Secondary aims were to assess whether length of time on the waiting list influenced quality of life and rate of deferral of surgery. METHODS: During the study period (August and September 2020) 843 patients (THA n = 394, KA n = 449) from ten centres in the UK reported their EuroQol five dimension (EQ-5D) scores and completed a waiting list questionnaire (2020 group). Patient demographic details, procedure, and date when listed were recorded. Patients scoring less than zero for their EQ-5D score were defined to be in a health state "worse than death" (WTD). Data from a retrospective cohort (January 2014 to September 2017) were used as the control group. RESULTS: The 2020 group had a significantly worse EQ-5D score compared to the control group for both THA (p < 0.001) and KA (p < 0.001). Over one-third (35.0%, n = 138/394) of patients waiting for a THA and nearly a quarter (22.3%, n = 100/449) for KA were in a health state WTD, which was significantly greater than the control group (odds ratio 2.30 (95% confidence interval (CI) 1.83 to 2.93) and 2.08 (95% CI 1.61 to 2.70), respectively; p < 0.001). Over 80% (n = 680/843) of the 2020 group felt that their quality of life had deteriorated while waiting. Each additional month spent on the waiting list was independently associated with a decrease in quality of life (EQ-5D: -0.0135, p = 0.004). There were 117 (13.9%) patients who wished to defer their surgery and the main reason for this was health concerns for themselves and or their family (99.1%, n = 116/117). CONCLUSION: Over one-third of patients waiting for THA and nearly one-quarter waiting for a KA were in a state WTD, which was approaching double that observed prior to the pandemic. Increasing length of time on the waiting list was associated with decreasing quality of life. Level of evidence: Level III retrospective case control study Cite this article: Bone Joint J 2021;103-B(4):672-680.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , COVID-19 , Acesso aos Serviços de Saúde , Indicadores Básicos de Saúde , Qualidade de Vida/psicologia , Listas de Espera , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/psicologia , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Análise Multivariada , Pandemias , Aceitação pelo Paciente de Cuidados de Saúde , Melhoria de Qualidade , Fatores de Tempo , Reino Unido/epidemiologia
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