Early failure associated with adverse reactions to metal debris is an emerging problem after hip resurfacing but the exact mechanism is unclear. We analysed our entire series of 660 metal-on-metal resurfacings (Articular Surface Replacement (ASR) and Birmingham Hip Resurfacing (BHR)) and large-bearing ASR total hip replacements, to establish associations with metal debris-related failures. Clinical and radiological outcomes, metal ion levels, explant studies and lymphocyte transformation tests were performed. A total of 17 patients (3.4%) were identified (all ASR bearings) with adverse reactions to metal debris, for which revision was required. This group had significantly smaller components, significantly higher acetabular component anteversion, and significantly higher whole concentrations of blood and joint chromium and cobalt ions than asymptomatic patients did (all p < 0.001). Post-revision lymphocyte transformation tests on this group showed no reactivity to chromium or cobalt ions. Explants from these revisions had greater surface wear than retrievals for uncomplicated fractures. The absence of adverse reactions to metal debris in patients with well-positioned implants usually implies high component wear. Surgeons must consider implant design, expected component size and acetabular component positioning in order to reduce early failures when performing large-bearing metal-on-metal hip resurfacing and replacement.

ARMD is a spectrum of changes comprising of pure metallosis, ALVAL and granulomatous inflammation. ALVAL, a distinctive inflammatory response seen in ARMD, is a precursor of lymphoid neogenesis. Lymphoid neogenesis documented in a variety of chronic inflammatory conditions most probably contributes to tissue necrosis and prosthetic failure seen in MoM hip arthroplasties. The role of vascular changes in contributing to necrosis is unclear at this stage.

No abstract

The impact of COVID-19 varies markedly, not only between individual patients but also between different populations. We hypothesised that differences in human leukocyte antigen (HLA) genes might influence this variation. Using next generation sequencing, we analysed the class I and class II classical HLA genes of 147 individuals of European descent experiencing variable clinical outcomes following COVID-19 infection. Forty-nine of these patients were admitted to hospital with severe respiratory disease. They had no significant pre-existing comorbidities. We compared the results to those obtained from a group of 69 asymptomatic hospital workers who evidence of COVID exposure based on blood antibody testing. Allele frequencies in both the severe and asymptomatic groups were compared to local and national healthy controls with adjustments made for age and sex. With the inclusion of hospital staff who had reported localised symptoms only (limited to loss of smell/taste, n = 13) or systemic symptoms not requiring hospital treatment (n = 16), we carried out ordinal logistic regression modelling to determine the relative influence of age, BMI, sex and the presence of specific HLA genes on symptomatology. We found a significant difference in the allele frequency of HLA-DRB1*04:01 in the severe patient compared to the asymptomatic staff group (5.1% vs. 16.7%, P = .003 after adjustment for age and sex). There was a significantly lower frequency of the haplotype DQA1*01:01-DQB1*05:01-DRB1*01:01 in the asymptomatic group compared to the background population (P = .007). Ordinal logistic regression modelling confirmed the significant influence of DRB1*04:01 on the clinical severity of COVID-19 observed in the cohorts. These alleles are found in greater frequencies in the North Western European population. This regional study provides evidence that HLA genotype influences clinical outcome in COVID-19 infection. Validation studies must take account of the complex genetic architecture of the immune system across different geographies and ethnicities.

ObjectiveTo determine whether elevated blood cobalt (Co) concentrations are associated with early failure of metal-on-metal (MoM) hip resurfacings secondary to adverse reaction to metal debris (ARMD).DesignCohort study.SettingSingle centre orthopaedic unit.ParticipantsFollowing the identification of complications potentially related to metal wear debris, a blood metal ion screening programme was instigated at our unit in 2007 for all patients with Articular Surface Replacement (ASR) and Birmingham MoM hip resurfacings. Patients were followed annually unless symptoms presented earlier. Symptomatic patients were investigated with ultrasound scan and joint aspiration. The clinical course of all 278 patients with ‘no pain’ or ‘slight/occasional’ pain and a Harris Hip Score greater than or equal to 95 at the time of venesection were documented. A retrospective analysis was subsequently conducted using mixed effect modelling to investigate the temporal pattern of blood Co levels in the patients and survival analysis to investigate the potential role of case demographics and blood Co levels as risk factors for subsequent failure secondary to ARMD.ResultsBlood Co concentration was a positive and significant risk factor (z=8.44, p=2×10–16) for joint failure, as was the device, where the Birmingham Hip Resurfacing posed a significantly reduced risk for revision by 89% (z=−3.445, p=0.00005 (95% CI on risk 62 to 97)). Analysis using Cox-proportional hazards models indicated that men had a 66% lower risk of joint failure than women (z=−2.29419, p=0.0218, (95% CI on risk reduction 23 to 89)).ConclusionsThe results suggest that elevated blood metal ion concentrations are associated with early failure of MoM devices secondary to adverse reactions to metal debris. Co concentrations greater than 20 µg/l are frequently associated with metal staining of tissues and the development of osteolysis. Development of soft tissue damage appears to be more complex with females and patients with ASR devices seemingly more at risk when exposed to equivalent doses of metal debris.