Emerging evidence indicates that a dynamic interplay between the immune system and adipocytes contributes to the disturbed homeostasis in adipose tissue of obese subjects. Recently, we observed ...IL‐6‐secretion by CD4+ T cells from the stromal vascular fraction (SVF) of the infrapatellar fat pad (IFP) of knee osteoarthritis patients directly ex vivo. Here we show that human IL‐6+CD4+ T cells from SVF display a more activated phenotype than the IL‐6− T cells, as evidenced by the expression of the activation marker CD69. Analysis of cytokines secretion, as well as expression of chemokine receptors and transcription factors associated with different Th subsets (Treg, Th1, Th2, Th17 and Tfh) revealed that IL‐6‐secreting CD4+ T cells cannot be assigned to a conventional Th subset. TCRβ gene analysis revealed that IL‐6+ and IL‐6−CD4+ T cells appear clonally unrelated to each other, suggesting a different specificity of these cells. In line with these observations, adipocytes are capable of enhancing IL‐6 production by CD4+ T cells. Thus, IL‐6+CD4+ T cells are TCRαβ T cells expressing an activated phenotype potentially resulting from an interplay with adipocytes that could be involved in the inflammatory processes in the OA joint.
T cells are present in adipose tissue. Characterization of CD4+ T cells in several adipose tissues led to the identification of a population of cells that secretes IL‐6 directly ex vivo, is in an activated state and interacts with adipocytes. These cells could contribute to adipose tissue inflammation.
Previous studies have shown accumulation and an enhanced proinflammatory profile of macrophages in adipose tissue of obese mice, indicating the presence of an interaction between adipocytes and ...macrophages in this tissue. However, the consequences of this interaction in humans are yet incompletely understood. In this study, we explored the modulating effects of adipocytes on the phenotype of macrophages in humans and studied the possible molecular pathways involved. Adipocyte-conditioned media (ACM) treatment of macrophages for 48 h strongly reduced the LPS-induced IL-12p40 secretion by macrophages, whereas the production of TNF-α and other cytokines remained largely unaffected. This effect was independent of the source of adipocytes. Interestingly, the level of inhibition correlated directly with body mass index (BMI) of the adipocyte donor. Because adipocytes release many different cytokines, adipokines, and lipids, we have separated the protein and lipid fractions of ACM, to obtain insight into the molecular nature of the soluble mediators underlying the observed effect. These experiments revealed that the inhibitory effect resided predominantly in the lipid fraction. Further studies revealed that PGE2 and linoleic and oleic acid were potent inhibitors of IL-12p40 secretion. Interestingly, concentrations of these ACM-derived lipids increased with increase in BMI of the adipocyte donor, suggesting that they could mediate the BMI-dependent effects of ACM. To our knowledge, these results provide first evidence that obesity-related changes in adipose tissue macrophage phenotype could be mediated by adipocyte-derived lipids in humans. Intriguingly, these changes appear to be different from those in murine obesity.
Abstract Background To describe the prevalence of self-reported knee joint instability in patients with pre-surgery knee osteoarthritis (OA) and to explore the associations between self-reported knee ...joint instability and radiological features. Methods A cross-sectional study including patients scheduled for primary Total Knee Arthroplasty (TKA). Self-reported knee instability was examined by questionnaire. Radiological features consisted of osteophyte formation and joint space narrowing (JSN), both scored on a 0 to three scale. Scores > 1 are defined as substantial JSN or osteophyte formation. Regression analyses were provided to identify associations of radiological features with self-reported knee joint instability. Results Two hundred and sixty-five patients (mean age 69 years and 170 females) were included. Knee instability was reported by 192 patients (72%). Substantial osteophyte formation was present in 78 patients (41%) reporting and 33 patients (46%) not reporting knee joint instability. Substantial JSN was present in 137 (71%) and 53 patients (73%), respectively. Self-reported knee instability was not associated with JSN (relative to score 0, odds ratios (95% CI) of score 1, 2 and 3 were 0.87 (0.30–2.54), 0.98 (0.38–2.52), 0.68 (0.25–1.86), respectively) or osteophyte formation (relative to score 0, odds ratios (95% CI) of score 1, 2 and 3 were 0.77 (0.36–1.64), 0.69 (0.23–1.45), 0.89 (0.16–4.93), respectively). Stratified analysis for pain, age and BMI showed no associations between self-reported knee joint instability and radiological features. Conclusion Self-reported knee joint instability is not associated with JSN or osteophyte formation.
Highlights • Possible to cut human interface tissue with a waterjet. • The required waterjet pressure to cut samples was between 10 and 12 MPa for the 0.2 mm nozzle and between 5 and 10 MPa for the ...0.6 mm nozzle. • Cutting bone or bone cement requires about 3 times higher waterjet pressure (30–50 MPa, depending on used nozzle diameter). • Waterjet cutting is considered to be a safe technique to be used for minimally invasive interface tissue removal.
To evaluate the effect of ACL deficiency on the in vivo changes in end-to-end distances and to determine appropriate graft fixation angles for commonly used tunnel positions in contemporary ACL ...reconstruction techniques.
Twenty-one patients with unilateral ACL-deficient and intact contralateral knees were included. Each knee was studied using a combined magnetic resonance and dual fluoroscopic imaging technique while the patients performed a dynamic step-up motion (~50° of flexion to extension). The end-to-end distances of the centers of the anatomic anteromedial (AM), posterolateral (PL) and single-bundle ACL reconstruction (SB-anatomic) tunnel positions were simulated and analyzed. Comparisons were made between the elongation patterns between the intact and ACL-deficient knees. Additionally, a maximum graft length change of 6% was used to calculate the deepest flexion fixation angle.
ACL-deficient knees had significantly longer graft lengths when compared with the intact knees for all studied tunnel positions (p < 0.01). The end-to-end distances for the AM, PL and SB-anatomic grafts were significantly longer between 0-30° of flexion when compared with the intact knee by p < 0.05 for all. Six percent length change occurred with fixation of the AM bundle at 30° of flexion, PL bundle at 10° and the SB-anatomic graft at 20°.
ACL-deficient knees had significantly longer in vivo end-to-end distances between 0°-30° of flexion for grafts at the AM, PL and SB-anatomic tunnel positions when compared with the intact knees. Graft fixation angles of <30° for the AM, <10° for the PL, and <20° for the SB-anatomic grafts may prevent permanent graft stretch.
The objective of this study was to identify risk factors for knee osteoarthritis (OA) development in a young to middle-aged population with sub-acute knee complaints. This, in order to define high ...risk patients who may benefit from early preventive or future disease modifying therapies. Knee OA development visible on radiographs and MR in 319 patients (mean age 41.5 years) 10 years after sub-acute knee complaints and subjective knee function (KOOS score) was studied. Associations between OA development and age, gender, activity level, BMI, meniscal or anterior cruciate ligament (ACL) lesions, OA in first-degree relatives and radiographic hand OA were determined using multivariable logistic regression analysis. OA on radiographs and MR in the TFC is associated with increased age (OR: 1.10, 95 % 1.04–1.16 and OR: 1.07, 95 % 1.02–1.13). TFC OA on radiographs only is associated with ACL and/or meniscal lesions (OR: 5.01, 95 % 2.14–11.73), presence of hand OA (OR: 4.69, 95 % 1.35–16.32) and higher Tegner activity scores at baseline before the complaints (OR: 1.20, 95 % 1.01–1.43). The presence of OA in the TFC diagnosed only on MRI is associated with a family history of OA (OR: 2.44, 95 % 1.18–5.06) and a higher BMI (OR: 1.13, 95 % 1.04–1.23). OA in the PFC diagnosed on both radiographs and MR is associated with an increased age (OR: 1.06, 95 % 1.02–1.12 and OR: 1.05, 95 % 1.00–1.09). PFC OA diagnosed on radiographs only is associated with a higher BMI (OR: 1.12, 95 % 1.02–1.22). The presence of OA in the PFC diagnosed on MR only is associated with the presence of hand OA (OR: 3.39, 95 % 1.10–10.50). Compared to normal reference values, the study population had significantly lower KOOS scores in the different subscales. These results show that knee OA development in young to middle aged patients with a history of sub-acute knee complaints is associated with the presence of known risk factors for knee OA. OA is already visible on radiographs and MRI after 10 years. These high risk patients may benefit from adequate OA management early in life.
To determine whether referral to MRI by the general practitioner (GP) is non-inferior to usual care (no access to MRI by GPs) in patients with traumatic knee complaints regarding knee-related daily ...function.
This was a multicentre, non-inferiority randomised controlled trial with 1-year follow-up. GPs invited eligible patients during or after their consultation. Eligible patients (18-45 years) consulted a GP with knee complaints due to a trauma during the previous 6 months. Patients allocated to the MRI group received an MRI at (median) 7 (IQR 1-33) days after the baseline questionnaire. Patients in the usual care group received information on the course of knee complaints, and a referral to a physiotherapist or orthopaedic surgeon when indicated. The primary outcome measure was knee-related daily function measured with the Lysholm scale (0 to 100; 100=excellent function) over 1 year, with a non-inferiority margin of 6 points.
A total of 356 patients were included and randomised to MRI (n=179) or usual care (n=177) from November 2012 to December 2015. MRI was non-inferior to usual care concerning knee-related daily function during 1-year follow-up, for the intention-to-treat (overall adjusted estimate: 0.33; 95% CI -1.73 to 2.39) and per-protocol (overall adjusted estimate: 0.06; 95% CI -2.08 to 2.19) analysis. There were no differences between both groups in the amount of patients visiting other healthcare providers.
MRI in general practice in patients with traumatic knee complaints was non-inferior to usual care regarding knee-related daily function during 1-year follow-up.
NTR3689.
Aseptic loosening is a major cause of failure for unicondylar knee arthroplasty (UKA). In total knee arthroplasty (TKA), early migration as measured with radiostereometric analysis (RSA) is a strong ...predictor of late revision for aseptic loosening of the tibial component. Migration in the first two years provides information on the fixation of an implant. However, the migration pattern of UKAs has not been systematically determined, and it is unclear if the migration pattern of UKAs is similar to that of TKAs. Therefore, the present meta-analysis aims to evaluate the migration patterns of tibial components of UKAs.
All RSA studies reporting on migration at two or more postoperative time-points following UKA were included. Pubmed, Web of Science, Cochrane, and Embase were searched up to April 2021. The risk of bias was assessed using the methodological score of the Assessment of Quality in Lower Limb Arthroplasty tool. All phases of the review were performed by two reviewers independently. A random-effects model was applied to pool the migration data.
The literature search yielded 3,187 hits, of which ten studies were included, comprising 13 study groups and 381 UKAs. The majority of the early migration occurred in the first 6 months postoperatively followed by a period of very little migration, similar to what is reported for TKAs. The pooled mean migration expressed as the maximum total point motion of all UKAs at 3 months, 6 months, 1 year, and 2 years was 0.43 mm (95% CI 0.38–0.48), 0.54 mm (95% CI 0.40–0.67), 0.59 mm (95% CI 0.52–0.66), and 0.61 mm (95% CI 0.55–0.68), respectively. Migration at one year and two years was higher than migration of TKAs as reported in previous studies. All-polyethylene UKAs migrated more at one year (0.69 mm; 95% CI 0.58–0.80) than metal-backed UKAs (0.52 mm; 95% CI 0.46–0.58).
The migration pattern of UKAs is comparable with that of TKAs in the first two years as both types of implants show initial migration in the first few months and very little migration thereafter. However, UKAs had higher migration at 1-year and 2-year follow-up.
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