The anterior transmuscular intrapelvic approach for the treatment of acetabular fractures-a new anterior surgical strategy.

The anterior ilioinguinal and the posterior Kocher-Langenbeck approach have long been the standard surgical approaches to the acetabulum. The last decade has witnessed the development of so-called intrapelvic approaches for anterior pathologies because they provide better exposure of the quadrilateral plate. Currently, the modified Stoppa approach and the pararectus approach are frequently used by surgeons for the treatment of acetabular fractures. We investigated an even more direct access to the entire anterior column and the quadrilateral plate via the abdominal wall muscles, between the incisions for the ilioinguinal and the pararectus approach.After intensive study of anatomic specimens, a cadaver dissection was performed prior to clinical application. The approach was then used in 20 patients who were assessed retrospectively.Postoperative CT scans showed that, according to the Matta scoring system, the quality of fracture reduction was "anatomical" (≤ 1 mm) in 12 (60%), "imperfect" (2-3 mm) in four (20%), and "poor" (> 3 mm) in four (20%) patients. Numerous minor complications were observed; the majority of these had resolved at the time of discharge.In conclusion, the anterior transmuscular intrapelvic approach (ATI) is a safe and effective alternative to the ilioinguinal and pararectal approaches, and may be regarded as an evolutionary advancement of traditional procedures.

Quality of life, infection control, and complication rates using a novel custom-made articulating hip spacer during two-stage revision for periprosthetic joint infection.

INTRODUCTION: Two-stage revision remains the gold standard treatment for most chronically infected and complex total hip arthroplasty infections. To improve patient outcome and reduce complication rates, we have developed a novel custom-made articulating hip spacer technique and present our short-term results. MATERIALS AND METHODS: Between November 2017 and November 2019, 27 patients (mean age 70 years) underwent two-stage revision for periprosthetic joint infection of the hip using the articulating spacer design described here. We retrospectively analyzed spacer-related complications as well as rates for complication, infection control, and implant survivorship after final reimplantation. Furthermore, we prospectively collected patient-reported health-related quality of life (HRQoL) scores prior to spacer implantation, with the spacer and after reimplantation of the new prosthesis. RESULTS: An additional round of spacer exchange was performed in two patients (8.3%), persistent wound discharge was the reason in both cases. We had one (4.2%) spacer-related mechanical complication, a dislocation that was treated with closed reduction. After reimplantation, infection control was achieved in 96% with an implant survivorship of 92% after a mean follow-up time of 19 (range 7-32, SD 7.2) months. While the scores for VR-12 MCS, VAS hip pain and patient-reported overall satisfaction significantly improved after first stage surgery, the scores for WOMAC, UCLA and VR-12 PCS significantly improved after second stage surgery. CONCLUSIONS: Our two-stage approach for periprosthetic joint infection shows high infection eradication and implant survivorship rates at short-term follow-up. Spacer-related complication rates were low, and we achieved high patient satisfaction rates and low pain levels already during the spacer period. To further simplify comparison between different spacer designs, we propose a new hip spacer classification system.

What Is the Long-term (27- to 32-year) Survivorship of an Uncemented Tapered Titanium Femoral Component and Survival in Patients Younger Than 50 Years?

BACKGROUND: Uncemented femoral components in primary THA are in widespread use, especially in patients younger than 50 years, but few studies have evaluated their survival into the late third and early fourth decade. QUESTIONS/PURPOSES: We evaluated (1) survivorship using femoral revision for any reason as the endpoint, (2) survivorship using femoral revision for aseptic loosening as the endpoint, (3) survival in patients younger than 50 years, (4) cumulative incidence of stem revision for periprosthetic femoral fracture and (5) the overall risk of revision (change of any part of the implanted components) at a minimum of 27 years of follow-up with an uncemented tapered titanium stem still in clinical use today. METHODS: We reviewed the clinical and radiographic results of 326 THAs performed in 326 patients (for 28 patients with bilateral THA, only the first hip was included in the analysis to ensure independent observations) using an uncemented grit-blasted, tapered collarless titanium alloy (TiAl6Nb7) stem between January 1985 and December 1989. In that same timeframe, we performed 1038 primary THAs. During that time, we used cementless stems in patients without severe femoral canal deformity and adequate bone stock for uncemented femoral fixation as determined by using the indication criteria described by the developer. In all, 34% (354 of 1038) were cementless; all cementless stems implanted during that time were the stem being studied here. No others were used. The mean (range) age at the time of surgery was 56 years (13-81 years). Sixty-seven patients were younger than 50 years at the time of primary THA. A competing risk survivorship analysis was used to estimate long-term survival. The minimum follow-up was 27 years (mean 28 years; range 27-32 years); at that time, 169 patients had died, and four patients were lost to follow-up. RESULTS: Survivorship at 28 years with revision of the femoral component for any reason as the endpoint was 87% (95% CI 83 to 90). Survivorship for femoral revision for aseptic loosening as the endpoint was 94% at 28 years (95% CI 90 to 96). Survival in patients younger than 50 years at the time of primary THA was 89% (95% CI 78 to 95) and 95% (95% CI 86 to 98) at 28 years for the endpoints of all stem revisions and aseptic stem loosening, respectively. The overall cumulative incidence of stem revision for periprosthetic femoral fracture was 4% (95% CI 2 to 7) at 28 years. The overall THA survival rate at 28 years with revision for any reason as the endpoint was 57% (95% CI 51 to 62). CONCLUSIONS: Uncemented femoral fixation of a tapered collarless titanium alloy stem was reliable into the early fourth decade, especially in patients younger than 50 years. Late stem failures in the third and early fourth decade were mainly because of periprosthetic femoral fracture, while aseptic loosening occurred in undersized stems during the early second decade. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Minimally invasive Oxford unicompartmental knee arthroplasty ensures excellent functional outcome and high survivorship in the long term.

PURPOSE: Whether unicompartimental or total knee arthroplasty is superior for treatment of anteromedial knee osteoarthritis, is still uncertain. Therefore, the purpose of this study was to evaluate clinical and radiological outcome as well as long-term survivorship of medial Oxford unicompartmental knee arthroplasty (OUKA) at an independent center with a minimum follow-up of 10 years. METHODS: This single-center retrospective cohort study reports the 10-15 years follow-up results of 113 consecutive patients (126 knees) after medial OUKA. Survivorship analysis was performed with several different endpoints and clinical outcome was measured using the Oxford Knee Score (OKS), American Knee Society Score (AKSS-O), range of motion (ROM), Tegner activity score and UCLA score. Radiological analysis was performed with focus on progression of arthritis in the lateral compartment. RESULTS: A total of 16 patients (16 knees) underwent revision surgery resulting in a survival rate of 92.4% at 10 years and 88.6% at 15 years with the endpoint device-related revisions. The main reason for revision surgery was progression of arthritis in five patients (31.3%) followed by persistency of pain in three patients (18.7%). Clinical outcome was good to excellent with an OKS of 39.9 at 11 years, an AKSS-O of 89.3 and a mean range of motion of 122°. The radiological analysis revealed a significant progression of degenerative changes in the lateral compartment, however without any impact on the functional outcome. CONCLUSION: Oxford UKA of the medial compartment ensures good long-term survivorship with an excellent functional outcome. Therefore, the results of this study support the continued use of OUKA in patients with anteromedial osteoarthritis. LEVEL OF EVIDENCE: Retrospective cohort study, Level III.

Cumulative Long-Term Incidence of Postoperative Periprosthetic Femoral Fractures Using an Uncemented Tapered Titanium Hip Stem: 26- to 32-Year Results.

BACKGROUND: Although falling is becoming a major problem in the elderly, little is known about the long-term incidence of postoperative periprosthetic femoral fractures (PFF) after total hip arthroplasty (THA) using uncemented stems with a minimum follow-up of 26 years postoperatively. METHODS: In a consecutive series, the cumulative incidence of PFF after uncemented THA using a straight, collarless, tapered titanium stem was retrospectively reviewed in 354 hips (326 patients). After a mean follow-up of 28 (26-32) years postoperatively, 179 hips had died and 5 hips had been lost to follow-up. Kaplan-Meier survival analysis was used to estimate cumulative percentage probability of PFF. RESULTS: At final follow-up, a total of 27 fractures in 27 patients had occurred. In 15 hips, the stem had to be revised, and in 10 the fracture was treated by open reduction and internal fixation. Two patients declined further surgery. The cumulative percentage probability of PFF was 1.6% (95% confidence interval, 0.7 to 3.8) at 10 years and 13.2% (95% confidence interval, 8.5 to 20.2) at 29 years after primary THA. There was no association between the occurrence of fracture and gender, age at primary THA, cup revision, or canal fill index. CONCLUSION: Our findings indicate that PFF is the major mode of failure in the long term after uncemented THA using a tapered titanium stem. More research is needed to evaluate the reasons and risk factors for PFF after THA, thus providing better prophylaxis for those at risk and to compare the long-term incidence using different fixation methods and implants. LEVEL OF EVIDENCE: IV.

Periprosthetic Bone Mineral Density Around Uncemented Titanium Stems in the Second and Third Decade After Total Hip Arthroplasty: A DXA Study After 12, 17 and 21 Years.

Implant failure and periprosthetic fractures because of periprosthetic bone loss are a major concern in total hip arthroplasty (THA). Hardly any clinical data exist on the long-term evolution of bone mineral density (BMD) around uncemented femoral implants. The question to address is whether relevant bone loss continues into third decade around well-fixed uncemented femoral implants. BMD around stable uncemented straight titanium femoral implants was assessed in a longitudinal cohort study. We included 142 hips of 128 patients and measured the development of the periprosthetic BMD using dual-energy X-ray absorptiometry. The baseline measurement was 12 years (t1) after the implantation of an uncemented femoral stem. Follow-up-measurements were performed at 17 (t2) and at 21 years (t3) after primary THA. The regions of interest (ROI) were selected conforming to Gruen et al. We acquired complete data including three consecutive measurements (t1, t2, t3) for 42 patients (49 hips). Performing radiographic evaluation at t1, t2 and t3, we found a regular bone-implant interface present in all cases. Significant decrease in BMD could be shown in ROI 1 (p = 0.0001; - 7.8%), 4 (p = 0.024; - 2.4%), 6 (p = 0.001; - 5.5%) and 7 (p < 0.0001; - 11.7%) between t1 and t3 and in ROI 1 (p = 0.002; - 3.7%), 2 (p = 0.046; - 3.6%), 4 (p = 0.002; - 2.7%) and 7 (p < 0.0001; - 8.0%) between t2 and t3. There were significant differences in overall bone density (netavg) between t1 and t3 (p = 0.001; - 3.6%) and between t2 and t3 (p = 0.020; - 2.1%). The data indicate clinically relevant changes of BMD especially in the proximal Gruen zones in the long-term after uncemented THA. Loss of periprosthetic BMD might be a risk factor for periprosthetic fractures.

Long-term follow-up after anterior cruciate ligament reconstruction using a press-fit quadriceps tendon-patellar bone autograft.

BACKGROUND: The use of a quadriceps tendon-patellar bone (QTPB) autograft provides an alternative procedure in primary reconstruction of the anterior cruciate ligament (ACL). Using the press-fit technique for femoral fixation and knotting over a bone bridge as well as additional spongiosa filling for tibial fixation can completely eliminate the need for fixation implants. The objective of this study was to evaluate the long-term clinical, functional and radiological results of this operating method. METHODS: Sixty-nine patients (27 female-42 male) were included in this study. Fifty-seven patients (83%) received a comprehensive follow-up review after an average period of 7.5 years (range: 7-8.7). All other patients were surveyed by telephone. Six patients (9%) suffered a re-rupture of the ACL graft caused by a new related trauma and were therefore excluded from the statistical analysis. RESULTS: Of all patients, 98% were satisfied with the operation. Normal or almost normal results were recorded in the subjective IKDC scores form by 88% of the patients. The Lysholm score demonstrated very good and good results in 83% of the patients. Only 1 patient reported minor complaints in the donor area. Seven (12%) patients developed Cyclops syndrome with limited knee extension. This complication was treated arthroscopically within the first year postoperatively. Their results on follow-up were not worse than the results of the patients without Cyclops syndrome. Regarding the 57 patients who received a comprehensive evaluation, the stability test with the KT-1000 Arthrometer yielded a difference of less than 3 mm in the contralateral comparison for 89% of the operated knees. The pivot-shift test was normal in 79% and almost normal in 21%. In the Single-leg Triple Hop Test, patients achieved an average of 98% of the hopping distance attained with the contralateral leg. The radiological examination revealed a slight deterioration in the Kellgren-Lawrence Score in 2 patients. CONCLUSION: The ACL reconstruction using the QTPB autograft performed with the press-fit technique leads to good results in comparison with published results of established procedures for primary ACL surgery using other autografts. Further investigations should involve comparative studies with the objective of providing evidence-based, individually adapted therapy for ACL rupture.

Long-Term Results of Acetabular Reconstruction Using Ganz Acetabular Rings.

BACKGROUND: Our study examines the long-term results of acetabular reconstruction using the Ganz acetabular reinforcement ring (GRR) in total hip arthroplasty. METHODS: Between 1998 and 2001, 135 hips (119 revision and 16 primary arthroplasties) were consecutively implanted with a GRR at our hospital. The average age was 65 years (range, 26-90). Clinical and radiographic evaluations were carried out. Long-term survivorship was estimated using a competing risks analysis, and multivariate survivorship using Cox regression model was used to identify risk factors for implant failure. RESULTS: At a mean follow-up of 16 years (range, 15-18), 3 patients were lost to follow-up and 19 had implant failure: 4 aseptic loosenings without re-revision, 4 septic, and 11 aseptic re-revisions. Survival was estimated at 86% after 16 years (95% confidence interval [CI], 78.5%-90.9%) using radiographic loosening or revision for any reason as the end point. Using aseptic loosening as the end point, the survival was estimated at 91.2% after 16 years (95% CI, 84.5%-95.0%). Multivariate analysis revealed that age at surgery was a significant risk factor for failure of the GRR. With acetabular revision or loosening as the end point, patients ≤60 years had 71.6% (95% CI, 53%-82.8%) and older patients had 92.2% (95% CI, 84%-96.2%) probability of implant survival after a mean 16-year follow-up. The median Harris Hip Scores and Western Ontario and McMaster Universities Osteoarthritis Index scores were 77 and 64.5, respectively, and mean Numerical Pain Rating Scale score was 1.6 at final follow-up. CONCLUSION: Our long-term study showed acceptable survival and functional results using the GRR in older patients, while young patients had less favorable survival.

Activated human B cells induce inflammatory fibroblasts with cartilage-destructive properties and become functionally suppressed in return.

BACKGROUND: Cross-talk between synovial fibroblasts (SF) and immune cells is suggested to play a crucial role in inflammation and chronification of rheumatoid arthritis (RA). The contribution of B cells in this process is poorly defined. METHODS: Here, primary B cells from healthy donors were polyclonally activated and cocultured with SF of non-synovitic origin from patients with osteoarthritis. RESULTS: In B-SF cocultures the concentrations of interleukin 6 (IL-6) and IL-8 increased manifold compared with single cultures even under physical separation and remained stable for several days after B-cell removal. Intracellular staining confirmed SF as key producers of IL-6 and IL-8, and B cells as main producers of tumour necrosis factor alpha (TNFα) and IL-1ß. Blocking experiments with a combination of anti-TNFα-antibodies and rIL-1RA significantly reduced SF cytokine production by up to 90%, suggesting that B-cell-derived TNFα and IL-1ß were crucial mediators of SF activation. Interestingly, B-cell cytokine production, CD25 expression and proliferation decreased in cocultures by at least 50%, demonstrating a negative regulatory loop towards the activated B cells. Inhibition of activin receptor-like kinase 5, a crucial component of the tumour growth factor ß (TGFß) signalling pathway, partly restored B-cell proliferation, suggesting a contribution of SF-derived TGFß in B-cell suppression. Besides cytokines, B-cell-activated SF also upregulated secretion of matrix metalloproteases such as MMP-3, thereby acquiring potential tissue destructive properties. This was confirmed by their invasion into human cartilage in the severe combined immunodeficiency mouse fibroblast invasion model in vivo. CONCLUSIONS: Interaction with activated B cells leads to conversion of non-arthritic SF into SF with a proinflammatory and aggressive RA-like phenotype, thereby suggesting a new, so far unrecognised role for B cells in RA pathogenesis.

Fluorescence activated enrichment of CD146+ cells during expansion of human bone-marrow derived mesenchymal stromal cells augments proliferation and GAG/DNA content in chondrogenic media.

BACKGROUND: While numerous subpopulations of BM-MSCs have been identified, the relevance of these findings regarding the functional properties remains mostly unclear. With regards to attempts of enhancing differentiation results by preselecting certain MSC subtypes, we have evaluated the efficiency of CD146 purification during expansion, and evaluated whether these measures enhanced MSC differentiation results. METHODS: Human MSCs were derived from bone marrow of six donors and cultured in two different culture media. After P1, MSCs were purified by either magnetic or fluorescence sorting for CD146, with unsorted cells as controls. Growth characteristics and typical MSC surface markers were assessed from P0 to P3. After P3, chondrogenic, osteogenic and adipogenic differentiation potential were assessed. RESULTS: Despite a high variability of CD146 expression among the donors, fluorescence sorting significantly increased the number of CD146+ cells compared to control MSCs, while magnetic sorting led to a lesser enrichment. Osteogenic and adipogenic differentiation potential was not affected by the sorting process. However, FACS-sorted cells showed significantly increased GAG/DNA content after chondrogenic differentiation compared to control MSCs. CONCLUSION: FACS sorting of CD146+ cells was more efficient than magnetic sorting. The underlying mechanism of increased GAG/DNA content after enrichment during expansion remains unclear, but may be linked to increased proliferation rates in these cells.

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

PURPOSE: Biological 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. METHODS: Four moderately conforming fixed-bearing implants were subjected to physiological loadings and motions for 5×10(6) 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. RESULTS: A polyethylene wear rate of 7.28 ± 0.27 mg/10(6) cycles was determined and the cumulative mass of released metals measured 1.63 ± 0.28 mg for cobalt, 0.47 ± 0.06 mg for chromium, 0.42 ± 0.06 mg for molybdenum and 1.28 ± 0.14 mg for titanium. CONCLUSION: For 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 12 % 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.

Different culture media affect growth characteristics, surface marker distribution and chondrogenic differentiation of human bone marrow-derived mesenchymal stromal cells.

BACKGROUND: Bone marrow-derived mesenchymal stromal cells (BM-MSCs) play an important role in modern tissue engineering, while distinct variations of culture media compositions and supplements have been reported. Because MSCs are heterogeneous regarding their regenerative potential and their surface markers, these parameters were compared in four widely used culture media compositions. METHODS: MSCs were isolated from bone marrow and expanded in four established cell culture media. MSC yield/1000 MNCs, passage time and growth index were observed. In P4, typical MSC surface markers were analysed by fluorescence cytometry. Additionally, chondrogenic, adipogenic and osteogenic differentiation potential were evaluated. RESULTS: Growth index and P0 cell yield varied importantly between the media. The different expansion media had a significant influence on the expression of CD10, CD90, CD105, CD140b CD146 and STRO-1. While no significant differences were observed regarding osteogenic and adipogenic differentiation, chondrogenic differentiation was superior in medium A as reflected by GAG/DNA content. CONCLUSIONS: The choice of expansion medium can have a significant influence on growth, differentiation potential and surface marker expression of mesenchymal stromal cells, which is of fundamental importance for tissue engineering procedures.

The Impact of 45S5-Bioactive Glass on Synovial Cells in Knee Osteoarthritis-An In Vitro Study.

Synovial inflammation in osteoarthritis (OA) is characterized by the release of cartilage-degrading enzymes and inflammatory cytokines. 45S5-bioactive glass (45S5-BG) can modulate inflammation processes; however, its influence on OA-associated inflammation has hardly been investigated. In this study, the effects of 45S5-BG on the release of cartilage-degrading metalloproteinases and cytokines from synovial membrane cells (SM) isolated from patients with knee OA was assessed in vitro. SM were cultivated as SM monocultures in the presence or absence of 45S5-BG. On day 1 (d1) and d7 (d7), the concentrations of Matrix Metalloproteinases (MMPs) and cytokines were assessed. In 45S5-BG-treated SM cultures, MMP9 concentration was significantly reduced at d1 and d7, whilst MMP13 was significantly increased at d7. Concentrations of interleukin (IL)-1B and C-C motif chemokine ligand 2 (CCL2) in 45S5-BG-treated SM cultures were significantly increased at both time points, as were interferon gamma (IFNG) and IL-6 at d7. Our data show an effect of 45S5-BG on SM activity, which was not clearly protective, anti-inflammatory, or pro-inflammatory. The influence of 45S5-BG on MMP release was more suggestive of a cartilage protective effect, but 45S5-BG also increased the release of pro-inflammatory cytokines. Further studies are needed to analyze the effect of BGs on OA inflammation, including the anti-inflammatory modification of BG compositions.

First-generation autologous chondrocyte implantation in patients with cartilage defects of the knee: 7 to 14 years' clinical and magnetic resonance imaging follow-up evaluation.

PURPOSE: The purpose of this study was to evaluate the overall long-term improvement of autologous chondrocyte implantation (ACI) treatment in terms of patient satisfaction, clinical assessment, and magnetic resonance imaging (MRI) evaluation. Furthermore, we aimed to assess the impact of independent variables on clinical outcomes and patient satisfaction. METHODS: We evaluated 23 patients (mean age, 30.5 ± 8.2 years) with full-thickness chondral lesions of the distal femur who underwent first-generation ACI with periosteum between 1997 and 2004. The Lysholm score, Tegner activity score, subjective International Knee Documentation Committee score, numeric rating scale score, and Short Form 36 score were used for clinical assessment preoperatively, at 1 year postoperatively, and at 7 to 14 years (mean, 9.9 years) after surgery. MRI was performed to evaluate the cartilage preoperatively and at final follow-up, by use of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. RESULTS: ACI resulted in a substantial improvement in all clinical outcome parameters, even as much as 14 years after implantation, although a small deterioration was noticed between intermediate and final evaluations in some outcome parameters. Of the patients, 73.1% stated that they would undergo the operation again. Younger patients with a shorter duration of preoperative symptoms and smaller defect sizes benefited most. MRI findings confirmed complete defect filling in 52.3% of the patients at final follow-up. CONCLUSIONS: Our long-term results confirm that first-generation ACI is an effective treatment for large full-thickness chondral and osteochondral lesions of the knee joint. Younger patients with a shorter duration of preoperative symptoms and smaller defect size benefited most in our study. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Efficacy of multidisciplinary treatment for patients with chronic low back pain: a prospective clinical study in 395 patients.

BACKGROUND: The effectiveness of multidisciplinary treatment programs varies throughout the literature, and it remains controversial how therapy outcome is affected by patients' individual parameters and which treatment settings work best. OBJECTIVES: We set out to examine the impact of patient variables on the effectiveness of a 3-week multidisciplinary treatment program in patients with chronic low back pain. By presenting effect sizes, we aimed to enable the comparison of our findings with other studies across disciplines. METHODS: Data on 395 patients were prospectively collected at study entry, at the end of the program (T1) and after 6 months' follow-up (T2). Relevant therapy outcomes were analyzed by presenting effect sizes with Cohen's d. Group comparisons were performed for sociodemographic and clinical features to determine the impact on therapy outcome. RESULTS: Medium effect sizes (d = -0.6 to -0.7) were shown for visual analog scale (VAS) after treatment and at T2, indicating clinically relevant pain relief. Significant changes in pain-related disability were observed immediately at T1 with a strong treatment effect (d = 0.8). Functional capacity was improved with low to medium effect sizes (0.4-0.5). Quality-of-life subscales (36-item Short Form Health Survey) improved significantly at T1 for physical function, vitality, and mental health (d = 0.5-0.8). Center for Epidemiological Studies - Depression Scale scores improved significantly with strong effect sizes of d = 0.7. Sociodemographic parameters displayed a significant impact on effect sizes for visual analog scale at T2, with females (d = -0.9), age group 30 to 39 years (d = -1), and patients with low physical job exposure (d = -0.9) benefiting most. An increase in number of pain locations (-0.7) and severity of accompanying pain (-0.7) in other body areas significantly impaired therapy outcome and effect sizes of VAS. CONCLUSIONS: Thus, multidisciplinary treatment ameliorates pain, functional restoration, and quality of life with medium to high effect sizes even for patients with a long history of chronic back pain. Effect sizes are higher than for monodisciplinary treatments and treatment effects remained stable at 6-month follow-up in a longitudinal uncontrolled study design. Thus, we believe that multidisciplinary treatment is vital for the treatment of patients with chronic low back pain. The impact of sociodemographic and pain-related parameters needs to be taken into account when including patients in an appropriate treatment program. We emphasize the presentation of effect sizes as a vital treatment evaluation to enable cross-sectional comparison of therapy outcomes.

CD8+ T Cells in OA Knee Joints Are Differentiated into Subsets Depending on OA Stage and Compartment.

Osteoarthritis (OA) is no longer considered a purely degenerative disease. OA is defined as a disease of the entire joint, in which inflammation occurs in various joint tissues. The overall aim of this study was to analyze the presence and polarization of CD8+ T cell subsets in OA knee joints, in relation to the OA stage and compartment (synovial fluid (SF), synovial membrane (SM,) peripheral blood (PB)). A quantitative flow analysis of CD8+ T cell subsets to compare the SF, SM, PB, was performed in patients with different stages of OA (early, unicondylar and bicondylar OA). Samples of the SF, SM and PB were harvested from a total of 55 patients at the time of surgery. Early OA was confirmed by independent surgeons intraoperatively. Uni- and bicondylar OA was confirmed and graded by two plane radiographs. Samples were analyzed by flow cytometry for surface markers, and cytokines by intracellular staining (ICS). CD8+ T cells were shown to be differentiated into pro-inflammatory IFN-γ producing Tc1 and IL-17A producing Tc17, as well as anti-inflammatory IL-4 producing Tc2. All CD8+ T cell subsets (Tc1, Tc17, and Tc2) were detected in both the SM and SF. The percentage of CD8+ T cell subsets of the total CD8+ T cell population was dependent on the OA stage and compartment. Compared with the peripheral blood (PB), the proportion of CD8+IFN-γ+ Tc1 and CD8+IL-17A+ Tc17 was significantly increased in OA SF. This was confirmed in our data for both early OA and end-stage OA. In the SM samples of end-stage OA patients, the proportion of CD8+IL-17A+ Tc17 was significantly increased compared to the PB. Comparing SF and SM samples of end-stage OA patients, the proportion of CD8+IFN-γ+ Tc1 was significantly increased in SF, whereas there were no differences concerning CD8+IL-4+ Tc2 and CD8+IL-17A+ Tc17. End-stage OA samples showed a significant increase of CD8+IL-4+ Tc2 in the SM for both unicondylar and bicondylar OA compared to early OA. CD8+ T cells infiltrating the SM and SF in OA knees are differentiated into IFN-γ-, IL-17A-, and IL-4-producing CD8+ T cell subsets (Tc1, Tc17, Tc2). This differentiation depends on the OA stage and OA compartment. Further investigation of CD8+ T cell subsets and their interaction with other inflammatory cells such as CD4+ T cells and macrophages may help to identify novel therapeutic anti-inflammatory strategies for containing OA progression.

Infiltration Profile of Regulatory T Cells in Osteoarthritis-Related Pain and Disability.

Emerging evidence indicates that regulatory T cells (Treg) intervene in the inflammatory processes that drive osteoarthritis (OA). However, whether polarized Tregs affect clinical features of the disease in the short- or long-term, and if so, what their role in OA-related pain and functional disability really is, remains elusive. Thus, the aim of the current study was to characterize the infiltration profile of Tregs in systemic (peripheral blood) and joint-derived (synovial fluid and synovial membrane) samples from patients with knee OA in relation to OA-induced symptoms. To this end, Treg infiltration (CD4+CD25+/high CD127low/-) was analyzed in matched samples of peripheral blood (PB), synovial fluid (SF) and synovial membrane (SM) from a total of 47 patients undergoing elective knee arthroplasty using flow cytometry. At the same time, knee pain and function were assessed and correlated with Treg proportions in different compartments (PB, SF, SM). Interestingly, matched-pair analysis revealed significantly higher Treg proportions in joint-derived samples than in PB, which was mainly attributed to the high Treg frequency in SF. Moreover, we found significant associations between infiltrating Tregs and OA-related symptoms which indicate that lower Treg proportions-especially in the SM-are related to increased pain and functional disability in knee OA. In conclusion, this study highlights the importance of local cellular inflammatory processes in OA pathology. Intra-articular Treg infiltration might play an important role not only in OA pathogenesis but also in the development of OA-related symptoms.

Mid- and long-term clinical results of surgical therapy in unicameral bone cysts.

BACKGROUND: Unicameral (or simple) bone cysts (UBC) are benign tumours most often located in long bones of children and adolescents. Pathological fractures are common, and due to high recurrence rates, these lesions remain a challenge to treat. Numerous surgical procedures have been proposed, but there is no general consensus of the ideal treatment. The aim of this investigation therefore was to study the long-term outcome after surgical treatment in UBC. METHODS: A retrospective analysis of 46 patients surgically treated for UBC was performed for short and mid-term outcome. Clinical and radiological outcome parameters were studied according to a modified Neer classification system. Long-term clinical information was retrieved via a questionnaire at a minimum follow-up of 10 years after surgery. RESULTS: Forty-six patients (17 female, 29 male) with a mean age of 10.0 ± 4.8 years and with histopathologically confirmed diagnosis of UBC were included. Pathological fractures were observed in 21 cases (46%). All patients underwent surgery for UBC (35 patients underwent curettage and bone grafting as a primary therapy, 4 curettage alone, 3 received corticoid instillation and 4 decompression by cannulated screws). Overall recurrence rate after the first surgical treatment was 39% (18/46), second (17.4% of all patients) and third recurrence (4.3%) were frequently observed and were addressed by revision surgery. Recurrence was significantly higher in young and in male patients as well as in active cysts. After a mean of 52 months, 40 out of 46 cysts were considered healed. Prognosis was significantly better when recurrence was observed later than 30 months after therapy. After a mean follow-up of 15.5 ± 6.2 years, 40 patients acknowledged clinically excellent results, while five reported mild and casual pain. Only one patient reported a mild limitation of range of motion. CONCLUSIONS: Our results suggest satisfactory overall long-term outcome for the surgical treatment of UBC, although short-and mid-term observation show a considerable rate of recurrence independent of the surgical technique.

Monocytes, Macrophages, and Their Potential Niches in Synovial Joints - Therapeutic Targets in Post-Traumatic Osteoarthritis?

Synovial joints are complex structures that enable normal locomotion. Following injury, they undergo a series of changes, including a prevalent inflammatory response. This increases the risk for development of osteoarthritis (OA), the most common joint disorder. In healthy joints, macrophages are the predominant immune cells. They regulate bone turnover, constantly scavenge debris from the joint cavity and, together with synovial fibroblasts, form a protective barrier. Macrophages thus work in concert with the non-hematopoietic stroma. In turn, the stroma provides a scaffold as well as molecular signals for macrophage survival and functional imprinting: "a macrophage niche". These intricate cellular interactions are susceptible to perturbations like those induced by joint injury. With this review, we explore how the concepts of local tissue niches apply to synovial joints. We introduce the joint micro-anatomy and cellular players, and discuss their potential interactions in healthy joints, with an emphasis on molecular cues underlying their crosstalk and relevance to joint functionality. We then consider how these interactions are perturbed by joint injury and how they may contribute to OA pathogenesis. We conclude by discussing how understanding these changes might help identify novel therapeutic avenues with the potential of restoring joint function and reducing post-traumatic OA risk.

Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis.

BACKGROUND: Investigating the pathophysiological mechanisms of early osteoarthritis (OA) is of utmost interest since this stage holds the strongest promise for therapeutic interventions. The aims of this study were to analyze if synovial inflammation is already present in early OA and to characterize the involved cell populations, by investigating synovial fluid (SF) and synovial membrane (SM) of early OA patients for the presence and polarization status of CD4 T cells. METHODS: A quantitative analysis of CD4+ T cell infiltration in SF and SM compared to peripheral blood (PB) was performed in patients with early stages of OA. We further investigated intracellular staining (ICS), surface marker, and chemokine receptor expression profiles of CD4+ T cells in SF, SM, and PB, as well as cytokine expression in native SF and PB. Matched samples of SF, SM, and PB were harvested from 40 patients with early OA at the time of surgery. Early OA was confirmed by independent surgeons intraoperatively. Samples were analyzed by flow cytometry for surface markers and cytokines, which are preferentially expressed by distinct T cell subsets (Th1, Th2, Th17, regulatory T cells). Furthermore, we analyzed native SF and PB supernatants using MACSPlex for multiple cytokine expression profiles. RESULTS: SF and SM showed a distinct infiltration of CD4+ T lymphocytes, with significantly increased expression of chemokine receptors CXCR3/CCR5, cytokine IFN-γ (preferentially expressed by Th1 cells), and CD161 (preferentially expressed by IL-17 producing Th17 cells) compared to PB. Furthermore, the percentage of CD4+ T cells polarized to Treg was significantly increased in SM compared to SF and PB. No significant differences were observed for CCR3 and CCR4 (preferentially expressed by Th2 cells), although IL-4 values were significantly higher in SM and SF compared to PB. Cytokine analysis showed comparable results between PB and SF, with only IL-6 being significantly increased in SF. CONCLUSIONS: Early OA joints show already significant inflammation through CD4+ T cell infiltration, with predominant Th1 cell polarization. Inflammation seems to be driven by direct proinflammatory cell interaction. Cytokine signaling seems to be negligible at the site of inflammation in early OA, with only IL-6 being significantly increased in SF compared to PB.