Joint stiffness is heritable and associated with fibrotic conditions and joint replacement

ObjectiveJoint stiffness is a common, debilitating, age-related symptom, which may be seen after total joint replacement (TJR). Stiffness also occurs in fibrotic conditions such as shoulder capsulitis and Dupuytren's contracture. We speculated that the two traits (TJR and fibrotic disease) are linked pathogenically.MethodsUsing the TwinsUK NIHR BRC BioResource we tested the hypotheses that 1) joint (hip and knee) stiffness, TJR (hip and knee), and fibrotic conditions are associated and 2) genetic factors contribute to them.ResultsParticipating twins (n = 9718) had completed self-reported questionnaires on the traits of interest. All three traits were significantly associated with increasing age and body mass index (BMI), as well as female sex, on univariate analysis. Multivariable logistic regression analyses showed a significant association between TJR and joint stiffness (OR = 3.96, 95% confidence interval, CI 2.77-5.68) and between fibrotic conditions and joint stiffness (OR = 2.39, 1.74-3.29), adjusting for age, sex, BMI and twin relatedness. Monozygotic versus dizygotic intraclass correlations gave heritability estimates for TJR = 46% and joint stiffness = 32%.ConclusionThat fibrotic conditions, joint stiffness and TJR are significantly associated suggests a common disease process, possibly fibrosis, which is genetically mediated

Universal heteroplasmy of human mitochondrial DNA.

Mammalian cells contain thousands of copies of mitochondrial DNA (mtDNA). At birth, these are thought to be identical in most humans. Here, we use long read length ultra-deep resequencing-by-synthesis to interrogate regions of the mtDNA genome from related and unrelated individuals at unprecedented resolution. We show that very low-level heteroplasmic variance is present in all tested healthy individuals, and is likely to be due to both inherited and somatic single base substitutions. Using this approach, we demonstrate an increase in mtDNA mutations in the skeletal muscle of patients with a proofreading-deficient mtDNA polymerase γ due to POLG mutations. In contrast, we show that OPA1 mutations, which indirectly affect mtDNA maintenance, do not increase point mutation load. The demonstration of universal mtDNA heteroplasmy has fundamental implications for our understanding of mtDNA inheritance and evolution. Ostensibly de novo somatic mtDNA mutations, seen in mtDNA maintenance disorders and neurodegenerative disease and aging, will partly be due to the clonal expansion of low-level inherited variants

Elective orthopaedic cancellations due to the COVID-19 pandemic: where are we now, and where are we heading?

Aims The primary aim is to estimate the current and potential number of patients on NHS England orthopaedic elective waiting lists by November 2020. The secondary aims are to model recovery strategies; review the deficit of hip and knee arthroplasty from National Joint Registry (NJR) data; and assess the cost of returning to pre-COVID-19 waiting list numbers. Methods A model of referral, waiting list, and eventual surgery was created and calibrated using historical data from NHS England (April 2017 to March 2020) and was used to investigate the possible consequences of unmet demand resulting from fewer patients entering the treatment pathway and recovery strategies. NJR data were used to estimate the deficit of hip and knee arthroplasty by August 2020 and NHS tariff costs were used to calculate the financial burden. Results By November 2020, the elective waiting list in England is predicted to be between 885,286 and 1,028,733. If reduced hospital capacity is factored into the model, returning to full capacity by November, the waiting list could be as large as 1.4 million. With a 30% increase in productivity, it would take 20 months if there was no hidden burden of unreferred patients, and 48 months if there was a hidden burden, to return to pre-COVID-19 waiting list numbers. By August 2020, the estimated deficits of hip and knee arthroplasties from NJR data were 18,298 (44.8%) and 16,567 (38.6%), respectively, compared to the same time period in 2019. The cost to clear this black log would be £198,811,335. Conclusion There will be up to 1.4 million patients on elective orthopaedic waiting lists in England by November 2020, approximate three-times the pre-COVID-19 average. There are various strategies for recovery to return to pre-COVID-19 waiting list numbers reliant on increasing capacity, but these have substantial cost implications. Cite this article: Bone Jt Open 2021;2(2):103–110

First-time revision knee arthroplasty using a hinged prosthesis

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