Aims. Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI). Methods. Blood and synovial fluid samples were collected prospectively from 195 patients undergoing primary or revision hip and knee arthroplasty. Patients were divided into five groups: 1) primary total hip and knee arthroplasty performed due to idiopathic osteoarthritis (OA; n = 60); 2) revision hip and knee arthroplasty performed due to aseptic failure of the implant (AR-TJR; n = 40); 3) patients with a confirmed diagnosis of chronic PJI awaiting surgery (n = 45); 4) patients who have finished the first stage of the PJI treatment with the use of cemented spacer and were qualified for replantation procedure (SR-TJR; n = 25), and 5) patients with rheumatoid arthritis undergoing primary total hip and knee arthroplasty (RA; n = 25). CLP concentrations were measured quantitatively in the blood and synovial fluid using an immunoturbidimetric assay. Additionally, blood and synovial CRP, blood interleukin-6 (IL-6), and ESR were measured, and a leucocyte esterase (LE) strip test was performed. Results. Patients with PJI had higher CLP concentrations than those undergoing aseptic revision in blood (median PJI 2.14 mg/l (interquartile range (IQR) 1.37 to 3.56) vs AR-TJR 0.66 mg/l (IQR 0.3 to 0.83); p < 0.001) and synovial fluid samples (median PJI 20.46 mg/l (IQR 14.3 to 22.36) vs AR-TJR 0.7 mg/l (IQR 0.41 to 0.95); p < 0.001). With a cut-off value of 1.0 mg/l, blood CLP showed a sensitivity, specificity, positive predictive value, and negative predictive value of 93.3%, 87.5%, 89.4%, and 92.1%, respectively. For synovial fluid with a cut-off value of 1.5 mg/l, these were 95.6%, 95%, 95.5%, and 95%, respectively. Conclusion. This small study suggests that synovial and blood CLP are useful markers in chronic PJI diagnosis with similar or higher sensitivity and specificity than routinely used markers such as CRP, ESR, IL-6, and LE. CLP was not useful to differentiate patients with PJI from those with rheumatoid arthritis. Cite this article: Bone Joint J 2021;103-B(1):46–55

Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases

Aims. Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss. Methods. Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed. Results. Combined deficiency of IL-1/IL-6 markedly ameliorated TNF-mediated arthritis and bilateral sacroiliitis, but without additive benefits compared to single IL-1 deficiency. This finding confirms the important role of IL-1 and the marginal role of IL-6 in TNF-driven pathways of local joint damage, but questions the efficacy of potential combinatorial therapies of IL-1 and IL-6 in treatment of RA. In contrast, combined deficiency of IL-1/IL-6 led to an additive protective effect on TNF-driven systemic bone loss compared to single IL-1 and IL-6 deficiency. This finding clearly indicates a common contribution of both IL-1 and IL-6 in TNF-driven systemic bone loss, and points to a discrepancy of cytokine dependency in local and systemic TNF-driven mechanisms of inflammatory arthritis. Conclusion. Combinatorial treatments in RA might provide different benefits to inflammatory local arthritis and systemic comorbidities. Cite this article: Bone Joint Res 2022;11(7):484–493

Aims. Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. Methods. We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation. Results. AOPPs promoted RA-FLS migration and invasion in vitro and significantly induced the messenger RNA (mRNA) and protein expression of TNF-α, IL-6, MMP-3, and MMP-13 in dose- and time-dependent manners. Moreover, AOPPs markedly activated the phosphorylation of nuclear factor-κB (NF-κB) p65 protein, which triggered inhibitory kappa B-alpha (IκBα) degradation, NF-κB p65 protein phosphorylation, and NF-κB p65 translocation into the nucleus. Furthermore, treatment with a neutralizing antibody specific to receptor for advanced glycation end products (RAGE) significantly suppressed aggressive behaviour and inflammation, decreased TNF-α, IL-6, MMP-3, and MMP-13 expression, and blocked AOPP-induced NF-κB pathway activation. Conclusion. The results indicate that AOPPs can enhance aggressive behaviour and the inflammatory response in RA-FLSs via the RAGE–NF-κB pathway. These results present AOPPs as a new class of potentially important mediators of progressive disease in RA patients. Cite this article: Bone Joint Res 2021;10(4):259–268

Aims. This systematic review asked which patterns of complications are associated with the three reverse total shoulder arthroplasty (RTSA) prosthetic designs, as classified by Routman et al, in patients undergoing RTSA for the management of cuff tear arthropathy, massive cuff tear, osteoarthritis, and rheumatoid arthritis. The three implant design philosophies investigated were medial glenoid/medial humerus (MGMH), medial glenoid/lateral humerus (MGLH), and lateral glenoid/medial humerus (LGMH). Methods. A systematic review of the literature was performed via a search of MEDLINE and Embase. Two reviewers extracted data on complication occurrence and patient-reported outcome measures (PROMs). Meta-analysis was conducted on the reported proportion of complications, weighted by sample size, and PROMs were pooled using the reported standardized mean difference (SMD). Quality of methodology was assessed using Wylde’s non-summative four-point system. The study was registered with PROSPERO (CRD42020193041). Results. A total of 42 studies met the inclusion and exclusion criteria. Rates of scapular notching were found to be significantly higher in MGMH implants (52% (95% confidence interval (CI) 40 to 63)) compared with MGLH ((18% (95% CI 6 to 34)) and LGMH (12% (95% CI 3 to 26)). Higher rates of glenoid loosening were seen in MGMH implants (6% (95% CI 3 to 10)) than in MGLH implants (0% (95% CI 0 to 2)). However, strength of evidence for this finding was low. No significant differences were identified in any other complication, and there were no significant differences observed in PROMs between implant philosophies. Conclusion. This systematic review has found significant improvement in PROMS and low complication rates across the implant philosophies studied. Scapular notching was the only complication found definitely to have significantly higher prevalence with the MGMH implant design. Cite this article: Bone Joint J 2021;103-B(5):813–821

Aims. The aim of this study is to define a core outcome set (COS) to allow consistency in outcome reporting amongst studies investigating the management of orthopaedic treatment in children with spinal dysraphism (SD). Methods. Relevant outcomes will be identified in a four-stage process from both the literature and key stakeholders (patients, their families, and clinical professionals). Previous outcomes used in clinical studies will be identified through a systematic review of the literature, and each outcome will be assigned to one of the five core areas, defined by the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT). Additional possible outcomes will be identified through consultation with patients affected by SD and their families. Results. Outcomes identified in these stages will be included in a two-round Delphi process that will involve key stakeholders in the management of SD. A final list including the identified outcomes will then be summarized in a consensus meeting attended by representatives of the key stakeholders groups. Conclusion. The best approach to provision of orthopaedic care in patients with SD is yet to be decided. The reporting of different outcomes to define success among studies, often based on personal preferences and local culture, has made it difficult to compare the effect of treatments for this condition. The development of a COS for orthopaedic management in SD will enable meaningful reporting and facilitate comparisons in future clinical trials, thereby assisting complex decision-making in the clinical management of these children. Cite this article: Bone Jt Open 2022;3(1):54–60

Aims. This study, using a surgeon-maintained database, aimed to explore the risk factors for surgery-related complications in patients undergoing primary cervical spine surgery for degenerative diseases. Methods. We studied 5,015 patients with degenerative cervical diseases who underwent primary cervical spine surgery from 2012 to 2018. We investigated the effects of diseases, surgical procedures, and patient demographics on surgery-related complications. As subcategories, the presence of cervical kyphosis ≥ 10°, the presence of ossification of the posterior longitudinal ligament (OPLL) with a canal-occupying ratio ≥ 50%, and foraminotomy were selected. The surgery-related complications examined were postoperative upper limb palsy (ULP) with a manual muscle test (MMT) grade of 0 to 2 or a reduction of two grade or more in the MMT, neurological deficit except ULP, dural tear, dural leakage, surgical-site infection (SSI), and postoperative haematoma. Multivariate logistic regression analysis was performed. Results. The significant risk factors (p < 0.050) for ULP were OPLL (odds ratio (OR) 1.88, 95% confidence interval (CI) 1.29 to 2.75), foraminotomy (OR 5.38, 95% CI 3.28 to 8.82), old age (per ten years, OR 1.18, 95% CI 1.03 to 1.36), anterior spinal fusion (OR 2.85, 95% CI 1.53 to 5.34), and the number of operated levels (OR 1.25, 95% CI 1.11 to 1.40). OPLL was also a risk factor for neurological deficit except ULP (OR 5.84, 95% CI 2.80 to 12.8), dural tear (OR 1.94, 95% CI 1.11 to 3.39), and dural leakage (OR 3.15, 95% CI 1.48 to 6.68). Among OPLL patients, dural tear and dural leakage were frequently observed in those with a canal-occupying ratio ≥ 50%. Cervical rheumatoid arthritis (RA) was a risk factor for SSI (OR 10.1, 95% CI 2.66 to 38.4). Conclusion. The high risk of ULP, neurological deficit except ULP, dural tear, and dural leak should be acknowledged by clinicians and OPLL patients, especially in those patients with a canal-occupying ratio ≥ 50%. Foraminotomy and RA were dominant risk factors for ULP and SSI, respectively. An awareness of these risks may help surgeons to avoid surgery-related complications in these conditions. Cite this article: Bone Joint J 2021;103-B(1):157–163

Aims. We report the medium-term outcomes of a consecutive series of 118 Zenith total ankle arthroplasties (TAAs) from a single, non-designer centre. Methods. Between December 2010 and May 2016, 118 consecutive Zenith prostheses were implanted in 114 patients. Demographic, clinical, and patient-reported outcome measures (PROMs) data were collected. The endpoint of the study was failure of the implant requiring revision of one or all of the components. Kaplan-Meier survival curves were generated with 95% confidence intervals (CIs) and the rate of failure calculated for each year. Results. Eight patients (ten ankles) died during follow-up, but none required revision. Of the surviving 106 patients (108 ankles: rheumatoid arthritis (RA), n = 15; osteoarthritis (OA), n = 93), 38 were women and 68 were men, with a mean age of 68.2 years (48 to 86) at the time of surgery. Mean follow-up was 5.1 years (2.1 to 9.0). A total of ten implants failed (8.5%), thus requiring revision. The implant survival at seven years, using revision as an endpoint, was 88.2% (95% CI 100% to 72.9%). There was a mean improvement in Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ) from 85.0 to 32.8 and visual analogue scale (VAS) scores from 7.0 to 3.2, and overall satisfaction was 89%. The three commonest complications were malleolar fracture (14.4%, n = 17), wound healing (13.6%, n = 16), and superficial infection (12.7%, n = 15). The commonest reason for revision was aseptic loosening. No patients in our study were revised for deep infection. Conclusion. Our results show that Zenith survival rates are comparable with those in the literature for other implants and in the National Joint Registry (NJR). Overall patient satisfaction was high as were functional outcomes. However, the data highlight potential complications associated with this surgery. The authors believe that these figures support ankle arthroplasty as an option in the treatment of ankle arthritis. Cite this article: Bone Joint J 2021;103-B(4):696–703

The purpose of this study was to evaluate the natural history of rheumatoid disease of the shoulder over an eight-year period. Our hypothesis was that progression of the disease is associated with a decrease in function with time. A total of 22 patients (44 shoulders; 17 women, 5 men, (mean age 63)) with rheumatoid arthritis were followed for eight years. All shoulders were assessed using the Constant score, anteroposterior radiographs (Larsen score, Upward-Migration-Index (UMI)) and ultrasound (US). At final follow-up, the Short Form-36, disabilities of the arm, shoulder and hand (DASH) Score, erythrocyte sedimentation rate and use of anti-rheumatic medication were determined. The mean Constant score was 72 points (50 to 88) at baseline and 69 points (25 to 100) at final follow-up. Radiological evaluation showed progressive destruction of the peri-articular structures with time. This progression of joint and rotator cuff destruction was significantly associated with the Constant score. However, at baseline only the extent of rotator cuff disease and the UMI could predict the Constant score at final follow-up. A plain anteroposterior radiograph of the shoulder is sufficient to assess any progression of rheumatoid disease and to predict functional outcome in the long term by using the UMI as an indicator of rotator cuff degeneration. Cite this article: Bone Joint J 2014;96-B:1520–4

There are no long-term published results on the survival of a third-generation cemented total shoulder replacement. We describe a clinical and radiological study of the Aequalis total shoulder replacement for a minimum of ten years. Between September 1996 and May 1998, 39 consecutive patients underwent a primary cemented total shoulder replacement using this prosthesis. Data were collected prospectively on all patients each year, for a minimum of ten years, or until death or failure of the prosthesis. At a follow-up of at least ten years, 12 patients had died with the prosthesis intact and two had emigrated, leaving 25 available for clinical review. Of these, 13 had rheumatoid arthritis and 12 osteoarthritis. One refused radiological review leaving 24 with fresh radiographs. Survivorship at ten years was 100% for the humeral component and 92% for the glenoid component. The incidence of lucent lines was low. No humeral component was thought to be at risk and only two glenoid components. The osteoarthritic group gained a mean 65° in forward flexion and their Constant score improved by a mean 41.4 points (13 to 55). The rheumatoid group gained a mean of 24° in flexion and their Constant score improved by 29.4 points. This difference may have been due to failure of the rotator cuff in 75% of the patients with rheumatoid arthritis. Thus a third-generation total shoulder replacement gives an excellent result in patients with osteoarthritis and an intact rotator cuff. Patients with rheumatoid arthritis have a 75% risk of failure of the rotator cuff at ten years

Aims. This paper aims to review the evidence for patient-related factors associated with less favourable outcomes following hip arthroscopy. Methods. Literature reporting on preoperative patient-related risk factors and outcomes following hip arthroscopy were systematically identified from a computer-assisted literature search of Pubmed (Medline), Embase, and Cochrane Library using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and a scoping review. Results. Assessment of these texts yielded 101 final articles involving 90,315 hips for qualitative analysis. The most frequently reported risk factor related to a less favourable outcome after hip arthroscopy was older age and preoperative osteoarthritis of the hip. This was followed by female sex and patients who have low preoperative clinical scores, severe hip dysplasia, altered hip morphology (excess acetabular retroversion or excess femoral anteversion or retroversion), or a large cam deformity. Patients receiving workers’ compensation or with rheumatoid arthritis were also more likely to have a less favourable outcome after hip arthroscopy. There is evidence that obesity, smoking, drinking alcohol, and a history of mental illness may be associated with marginally less favourable outcomes after hip arthroscopy. Athletes (except for ice hockey players) enjoy a more rapid recovery after hip arthroscopy than non-athletes. Finally, patients who have a favourable response to local anaesthetic are more likely to have a favourable outcome after hip arthroscopy. Conclusion. Certain patient-related risk factors are associated with less favourable outcomes following hip arthroscopy. Understanding these risk factors will allow the appropriate surgical indications for hip arthroscopy to be further refined and help patients to comprehend their individual risk profile. Cite this article: Bone Joint J 2020;102-B(7):822–831

Aims. The aim of this study was to evaluate the differences in revision and complication rates, functional outcomes, and radiological outcomes between cemented and press-fit humeral stems in primary anatomical total shoulder arthroplasty (TSA). Materials and Methods. A comprehensive systematic review and meta-analysis was conducted searching for studies that included patients who underwent primary anatomical TSA for primary osteoarthritis or rheumatoid arthritis. Results. There was a total of 36 studies with 927 cemented humeral stems and 1555 press-fit stems. The revision rate was 5.4% (95% confidence interval (CI) 3.9 to 7.4) at a mean of 89 months for cemented stems, and 2.4% (95% CI 1.1 to 4.7) at a mean of 40 months for press-fit stems. A priori subgroup analysis to control for follow-up periods demonstrated similar revision rates: 2.3% (95% CI 1.1 to 4.7) for cemented stems versus 1.8% (95% CI 1.4 to 2.9) for press-fit stems. Exploratory meta-regression found that longer follow-up was a moderating variable for revision (p = 0.003). Conclusion. Cement fixation had similar revision rates when compared to press-fit stems at short- to midterm follow-up. Rotator cuff pathology was a prevalent complication in both groups but is likely not related to fixation type. Overall, with comparable revision rates, possible easier revision, and decreased operative time, humeral press-fit fixation may be an optimal choice for primary anatomical TSA in patients with sufficient bone stock. Cite this article: Bone Joint J 2019;101-B:1107–1114

Aims

The aim of this study is to report the implant survival and factors associated with revision of total elbow arthroplasty (TEA) using data from the Dutch national registry.

The December 2012 Research Roundup. 360. looks at: whether the rheumatoid factor is just a ‘quick test’; osteonecrosis in smokers; pasteurisation effect on bone reconstruction; venous thromboembolism risk in rheumatoids; whether stem cells reverse age-related osteopenia; the effect of running on rat knees; rapid fracture healing in rats with ultrasound; magnetic stem cells; and the safety of surgery

Aims

Despite numerous studies focusing on periprosthetic joint infections (PJIs), there are no robust data on the risk factors and timing of metachronous infections. Metachronous PJIs are PJIs that can arise in the same or other artificial joints after a period of time, in patients who have previously had PJI.