Babak Moradi

Efficacy of different types of aerobic exercise in fibromyalgia syndrome: a systematic review and meta-analysis of randomised controlled trials

IntroductionThe efficacy and the optimal type and volume of aerobic exercise (AE) in fibromyalgia syndrome (FMS) are not established. We therefore assessed the efficacy of different types and volumes of AE in FMS.MethodsThe Cochrane Library, EMBASE, MEDLINE, PsychInfo and SPORTDISCUS (through April 2009) and the reference sections of original studies and systematic reviews on AE in FMS were systematically reviewed. Randomised controlled trials (RCTs) of AE compared with controls (treatment as usual, attention placebo, active therapy) and head-to-head comparisons of different types of AE were included. Two authors independently extracted articles using predefined data fields, including study quality indicators.ResultsTwenty-eight RCTs comparing AE with controls and seven RCTs comparing different types of AE with a total of 2,494 patients were reviewed. Effects were summarised using standardised mean differences (95% confidence intervals) by random effect models. AE reduced pain (-0.31 (-0.46, -0.17); P < 0.001), fatigue (-0.22 (-0.38, -0.05); P = 0.009), depressed mood (-0.32 (-0.53, -0.12); P = 0.002) and limitations of health-related quality of life (HRQOL) (-0.40 (-0.60, -0.20); P < 0.001), and improved physical fitness (0.65 (0.38, 0.95); P < 0.001), post treatment. Pain was significantly reduced post treatment by land-based and water-based AE, exercises with slight to moderate intensity and frequency of two or three times per week. Positive effects on depressed mood, HRQOL and physical fitness could be maintained at follow-up. Continuing exercise was associated with positive outcomes at follow-up. Risks of bias analyses did not change the robustness of the results. Few studies reported a detailed exercise protocol, thus limiting subgroup analyses of different types of exercise.ConclusionsAn aerobic exercise programme for FMS patients should consist of land-based or water-based exercises with slight to moderate intensity two or three times per week for at least 4 weeks. The patient should be motivated to continue exercise after participating in an exercise programme.

Wear analysis of unicondylar mobile bearing and fixed bearing knee systems: a knee simulator study.

Unicondylar knee arthroplasty is an attractive alternative to total knee arthroplasty for selected patients with osteoarthritis. Mobile bearing knee designs have been developed to improve knee kinematics, lower contact stresses and reduced wear of ultra-high molecular weight polyethylene compared with fixed bearing designs. This study compared in vitro wear behavior of fixed and mobile unicondylar bearing designs. Analysis was performed using a force-controlled AMTI knee simulator according to ISO 14243-1:2002(E). The wear volume of the implants was determined gravimetrically. Optical surface characterization and an estimation of wear particle size and morphology were performed. Implant kinematic data for both designs were determined. The wear rates averaged 10.7 ± 0.59 mg per 10(6) cycles for the medial and 5.38 ± 0.63 mg per 10(6) cycles for the lateral components of the mobile bearings, compared with 7.51 ± 0.29 mg per 10(6) cycles and 3.04 ± 0.35 mg per 10(6) cycles for the fixed bearings. The mobile bearings therefore exhibited higher wear rates (P<0.01) compared with the fixed bearings. The tibial polyethylene inserts of the mobile bearings showed pronounced backside wear at the inferior surface. The kinematics of both designs was similar. However, anterior-posterior translation was lower in the mobile bearings. The wear particles were mainly elongated and small in size for both designs (P=0.462). This study shows that wear may play an important role in unicondylar mobile bearing knee designs. Advantages of unicondylar mobile designs compared with fixed bearing designs, which have been proposed in terms of wear behavior and improved kinematics, could not be confirmed.

Activation of Matrix Metalloproteinases 2, 9, and 13 by Activated Protein C in Human Osteoarthritic Cartilage Chondrocytes

Levels of activated protein C (APC) are elevated in the synovial fluid of patients with osteoarthritis (OA), and increased APC levels are correlated with the levels of active matrix metalloproteinase 2 (MMP‐2). This study sought to investigate whether APC is a relevant protein for activation of MMPs in the degradation of human OA cartilage, and to elucidate its mechanisms of action.

Depletion of Protease-Activated Receptor 2 but Not Protease-Activated Receptor 1 May Confer Protection Against Osteoarthritis in Mice Through Extracartilaginous Mechanisms

To explore the involvement of protease‐activated receptor 1 (PAR‐1) and PAR‐2 in the pathologic processes of osteoarthritis (OA) and to identify the cells/tissues primarily affected by ablation of PAR‐1 or PAR‐2 in mice.

Unicompartmental and bicompartmental knee osteoarthritis show different patterns of mononuclear cell infiltration and cytokine release in the affected joints

It is still controversial which cell types are responsible for synovial inflammation in osteoarthritic (OA) joints. The aim of this study was to quantify the mononuclear cell populations and their cytokines in patients with different knee OA subtypes. Synovial membrane (SM), synovial fluid (SF) and peripheral blood (PB) were harvested from patients with unicompartmental (UC) and bicompartmental (BC) knee OA. Frequencies of mononuclear cells were assessed by flow cytometry in PB and SM. Naive SF samples were analysed for a broad variety of cytokines by multiplex analysis. SM of both groups displayed a distinct mononuclear cell infiltration, with CD14+ macrophages being the major cell population, followed by CD4+ T cells and only small numbers of CD8+ T, CD19+ B and CD16+CD56+ natural killer (NK) cells. Between the two groups, SM of BC OA showed significantly higher amounts of mononuclear cells (135·7u2009±u2009180 versus 805u2009±u2009675 cells/mg, Pu2009=u20090·0009) and higher CD4+ T cell presence (3·4u2009±u20094·6 versus 9·1u2009±u20097·5%, Pu2009=u20090·0267). SF of BC OA displayed significantly higher concentrations for a number of proinflammatory cytokines [CXCL1, eotaxin, interferon (IFN)‐γ, interleukin (IL)‐7, IL‐8, IL‐9, IL‐12]. UC and BC OA show significant differences in their synovial inflammatory pattern. Whereas in UC OA CD14+ macrophages are the predominant cell population, BC OA has a higher inflammatory profile and seems to be driven by CD14+ macrophages and CD4+ T cells. Inclusion of clinical information into the analysis of cellular and molecular results is pivotal in understanding the pathophysiology of OA.

Wear in total knee arthroplasty—just a question of polyethylene?: Metal ion release in total knee arthroplasty

PurposeBiological reactions against wear particles are a common cause for revision in total knee arthroplasty. To date, wear has mainly been attributed to polyethylene. However, the implants have large metallic surfaces that also could potentially lead to metal wear products (metal ions and debris). The aim of this study was to determine the local release of cobalt, chromium, molybdenum and titanium in total knee arthroplasty during a standard knee wear test.MethodsFour moderately conforming fixed-bearing implants were subjected to physiological loadings and motions for 5×106 walking cycles in a knee wear simulator. Polyethylene wear was determined gravimetrically and the release of metallic wear products was measured using high resolution-inductively coupled plasma-mass spectrometry.ResultsA polyethylene wear rate of 7.28u2009±u20090.27xa0mg/106xa0cycles was determined and the cumulative mass of released metals measured 1.63u2009±u20090.28xa0mg for cobalt, 0.47u2009±u20090.06xa0mg for chromium, 0.42u2009±u20090.06xa0mg for molybdenum and 1.28u2009±u20090.14xa0mg for titanium.ConclusionFor other metallic implants such as metal-on-metal total hip arthroplasty, the metal wear products can interact with the immune system, potentially leading to immunotoxic effects. In this study about 12xa0% by weight of the wear products were metallic, and these particles and ions may become clinically relevant for patients sensitive to these materials in particular. Non-metallic materials (e.g. ceramics or suitable coatings) may be considered for an alternative treatment for those patients.

The impact of pain spread on the outcome of multidisciplinary therapy in patients with chronic musculoskeletal pain – A prospective clinical study in 389 patients

Background: Musculoskeletal pain represents a continuous process ranging from single‐site to multiple‐site pain, with an increase in pain sites accompanied by an increasing risk of chronification and the development of further comorbidities. Within this context, the impact of pain spread on therapy outcome is still unknown.

The impact of pathological fractures on therapy outcome in patients with primary malignant bone tumours

The primary objective of this study was to investigate the implications of pathological fractures on therapy outcome in patients with primary malignant bone tumours and to determine whether limb salvage can be safely performed. A retrospective analysis of 447 patients with primary malignant bone tumours, treated between 1985 and 2005, was performed. Multivariate Cox regression analysis was used to investigate the influence of pathological fractures and further independent variables on survival rate. In 52 of the 447 patients, the primary malignant bone tumour was complicated by a pathological fracture. These fractures were more common in malignant fibrous histiocytoma (MFH) of the bone and in the tumour stages IIa/b and III. Ablative surgery was performed in ten patients and limb salvage surgery in 42 patients. The mortality risk for patients with pathological fractures was significantly increased by a factor of 1.82 (pu2009=u20090.015), and overall duration of survival was significantly lower in the fracture group, with a median of 6.2xa0years (pu2009<u20090.00001). In univariate and multivariate analysis, fracture, higher tumour stages and resection margins remained a significant predictor of worse survival. Overall survival, rate of local recurrence and distant metastases were not affected by the type of surgical treatment selected; there was no difference between the patients who underwent limb salvage and those who underwent an amputation. Pathological fracture in patients with primary malignant bone tumours is a predictor of worse survival and significantly increases mortality risk. Reconstructive surgery did not influence the survival rate, showing that limb salvage therapy is safe when adequate resection margins are achieved.

The value of physical performance tests for predicting therapy outcome in patients with subacute low back pain: a prospective cohort study

Considering the enormous costs of intensive multidisciplinary treatment, predictive tests for therapy outcome are needed to evaluate patients’ performance potential and increase cost effectiveness. Somatic parameters are commonly used to evaluate health status and serve as an additional means of forecasting the prognosis, yet little is known of their validity. In this study, we investigated the prognostic value of somatic parameters regarding the outcome of multidisciplinary treatment in patients with subacute low back pain. The study was designed as a prospective cohort study of 162 patients. Somatic parameters were assessed with three physical performance tests (Villiger test, Oesch test, Biering–Sørensen test) before treatment (T0), after 3xa0weeks’ inpatient therapy (T1) and at 6-month follow-up (T2). Psychometric characteristics of subjective pain perception (VAS), a pain disability index (PDI) and a physical capability index (FFbH-R) were recorded. Correlation coefficients between the physical performance test scores and psychometric characteristics were calculated. To predict therapy outcome, discriminant analyses were performed. A control group (nxa0=xa030) was evaluated at similar time points without receiving any therapy. Our results demonstrate good discrimination between patients and controls by means of the investigated performance tests and exhibit a significant negative correlation with the psychometric data. Lower outcome values at study entry correlated with higher pain intensity and disability after multidisciplinary treatment. However, the statistical magnitude of correlation was relatively low and further discriminant analysis did not reveal any predictive value. Consequently the physical performance tests do not have a prognostic value regarding therapy outcome.

The influence of bone marrow- and synovium-derived mesenchymal stromal cells from osteoarthritis patients on regulatory T cells in co-culture.

There is increasing evidence that inflammation in the synovium plays a major role in the progression of osteoarthritis (OA). However, the immunogenic properties of mesenchymal stromal cells (MSCs), which are considered to regulate immunity in various diseases, remain largely unknown in OA. The purpose of this study was to determine the influence of MSCs from OA patients on regulatory T cells (Tregs) in an allogeneic co‐culture model. Bone marrow (BM) and synovial membrane (SM) were harvested from hip joints of OA patients and co‐cultured with lymphocytes enriched in CD4+CD25+CD127– regulatory T cells (Treg+LC) from healthy donors. Treg proportions and MSC markers were assessed by flow cytometry. Cytokine levels were assessed after 2 and 5 days of co‐cultivation. Additionally, Treg+LC cultures were analysed in the presence of interleukin (IL)‐6 and MSC‐supernatant complemented medium. B‐MSCs and S‐MSCs were able to retain the Treg proportion compared to lymphocyte monocultures. T cell–MSC co‐cultures showed a significant increase of IL‐6 compared to MSC cultures. S‐MSCs produced higher amounts of IL‐6 compared to B‐MSCs, both in single and T cell co‐cultures. The effect of retaining the Treg percentage could be reproduced partially by IL‐6 addition to the medium, but could only be observed fully when using MSC culture supernatants. Our data demonstrate that retaining the Treg phenotype in MSC–T cell co‐cultures can be mediated by MSC derived from OA patients. IL‐6 plays an important role in mediating these processes. To our knowledge, this study is the first describing the interaction of MSCs from OA patients and Tregs in an allogeneic co‐culture model.