Risk for re-revision and type of antibiotic-loaded bone cement in hip or knee arthroplasty revisions: report of the Dutch Arthroplasty Register.

BACKGROUND AND PURPOSE: High-dose dual antibiotic-loaded bone cement (ALBC) may reduce the risk of revision after total hip and knee replacements. The aim of our study therefore was to determine the risk of re-revision following first time aseptic hip or knee revision using single versus dual ALBC. PATIENTS AND METHODS: Patients from the Dutch Arthroplasty Register treated from 2007 to 2018 with first time cemented aseptic hip (n = 2,529) or knee revisions (n = 7,124) were incorporated into 2 datasets. The primary endpoint of this observational cohort study was subsequent all-cause re-revision. Multivariable Cox proportional hazard and competing risk was analyzed for both groups. RESULTS: There was no difference in re-revision rate (any reason) with single versus dual ALBC (hazard ratio 1.06, 95% confidence interval [CI] 0.83-1.35 for hip and 0.93, CI 0.80-1.07 for knee revisions). The 10-year crude cumulative re-revision rate also showed no differences for single versus dual ALBC use. The crude cumulative 7-year THA re-revision and 9-year TKA re-revision rates did not show any difference in implant survival for common cement types used. CONCLUSION: We could not confirm the potential benefit of using dual ALBC compared with single ALBC for aseptic hip and knee revisions.

Wound drainage after arthroplasty and prediction of acute prosthetic joint infection: prospective data from a multicentre cohort study using a telemonitoring app.

Background: Differentiation between uncomplicated and complicated postoperative wound drainage after arthroplasty is crucial to prevent unnecessary reoperation. Prospective data about the duration and amount of postoperative wound drainage in patients with and without prosthetic joint infection (PJI) are currently absent. Methods: A multicentre cohort study was conducted to assess the duration and amount of wound drainage in patients after arthroplasty. During 30 postoperative days after arthroplasty, patients recorded their wound status in a previously developed wound care app and graded the amount of wound drainage on a 5-point scale. Data about PJI in the follow-up period were extracted from the patient files. Results: Of the 1019 included patients, 16 patients (1.6 %) developed a PJI. Minor wound drainage decreased from the first to the fourth postoperative week from 50 % to 3 %. Both moderate to severe wound drainage in the third week and newly developed wound drainage in the second week after a week without drainage were strongly associated with PJI (odds ratio (OR) 103.23, 95 % confidence interval (CI) 26.08 to 408.57, OR 80.71, 95 % CI 9.12 to 714.52, respectively). The positive predictive value (PPV) for PJI was 83 % for moderate to heavy wound drainage in the third week. Conclusion: Moderate to heavy wound drainage and persistent wound drainage were strongly associated with PJI. The PPV of wound drainage for PJI was high for moderate to heavy drainage in the third week but was low for drainage in the first week. Therefore, additional parameters are needed to guide the decision to reoperate on patients for suspected acute PJI.

Association between Baseline Osteoarthritic Features on MR Imaging and Clinical Outcome after Genicular Artery Embolization for Knee Osteoarthritis.

PURPOSE: To explore the association between baseline osteoarthritis (OA)-related magnetic resonance (MR) imaging features and pain reduction after genicular artery embolization (GAE) in patients with mild-to-moderate symptomatic knee OA resistant to conservative therapy. MATERIALS AND METHODS: This was a retrospective analysis of patients with mild-to-moderate symptomatic knee OA treated with GAE using imipenem-cilastatin sodium. The clinical outcome was scored at baseline and 6 months after treatment using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). MR images were scored using the MR imaging osteoarthritis knee score. Linear regression was used to evaluate associations of before-treatment MR imaging scores with WOMACpain and WOMACtotal reduction after 6 months. RESULTS: Fifty-four patients (22.2% male; median age, 69.4 years; median WOMACpain at baseline, 12) were evaluated. Of all OA features scored, a higher cartilage full-thickness defect score showed the strongest association with less reduction of both WOMACpain (B,-0.63 [95% confidence interval (CI), -0.91 to -0.34]; P < .001) and WOMACtotal scores (B, -1.77 [95% CI, -2.87 to -0.67]; P < .001) following treatment. The presence of grade 2-3 effusion synovitis (B, -2.99 [95% CI, -5.39 to -0.60]) bone marrow lesions (B, -0.52 [95% CI, -0.86 to -0.19]), osteophytes (B, -0.21 [95% CI, -0.36 to -0.06]), and cartilage defect surface area score (B, -0.25 [95% CI -0.42 to -0.08]) all showed a significant association with less WOMACpain reduction (all P < .05). CONCLUSIONS: In patients with mild-to-moderate symptomatic knee OA treated with GAE, the presence and severity of full-thickness cartilage defects, effusion synovitis, bone marrow lesions, osteophytes, and cartilage surface area scores at baseline are associated with less favorable clinical outcomes at 6 months.

Routine Fracture Fixation for a Periprosthetic Hip Fracture Below Birmingham Hip Resurfacing: A Case Report.

CASE: We present a case of a 56-year-old man who sustained a basal cervical periprosthetic fracture around a well-fixed metal-on-metal hip resurfacing arthroplasty (MoMHRA). Although several fixation methods have been described, there seems to be no consensus about the optimal fixation method for fractures around MoMHRAs. This fracture could be regarded as a Vancouver type-B1 or -C periprosthetic fracture, so we successfully treated our patient in a standard way with a dynamic hip screw (DHS) and one cannulated hip screw. CONCLUSION: We describe DHS fixation as a successful treatment option for periprosthetic hip fractures around well-fixed MoMHRA.

Quantitative subchondral bone perfusion imaging in knee osteoarthritis using dynamic contrast enhanced MRI.

OBJECTIVE: Subchondral bone changes, characterized by increased bone turnover and vascularity, are believed to stimulate progression and pain in knee osteoarthritis (OA). The objective of this study was to evaluate the bone perfusion in knee OA using quantitative dynamic contrast enhanced MRI (DCE-MRI). DESIGN: Unicompartmental knee OA patients were included and underwent 3 Tesla DCE-MRI and T2-weighted MRI. Quantitative DCE-MRI analysis of Ktrans and Kep, representing perfusion parameters, was performed to evaluate differences between the most and least affected knee compartment. First, DCE-MRI parameter differences between epimetaphyseal and subchondral bone in both femur and tibia were assessed. Second, DCE-MRI parameters in subchondral bone marrow lesions (BMLs) were compared to surrounding subchondral bone without BMLs. RESULTS: Twenty-three patients were analyzed. Median Ktrans and Kep in epimetaphyseal bone were significantly higher (p < 0.05) in the most affected (Ktrans: 0.014; Kep: 0.054 min-1) compared to least affected (Ktrans: 0.010; Kep: 0.016 min-1) compartment. For subchondral bone, DCE-MRI parameters were significantly higher (p < 0.05) in the most affected (Ktrans: 0.019; Kep: 0.091 min-1) compared to least affected (Ktrans: 0.014; Kep: 0.058 min-1) compartment as well. Subchondral BMLs detected on fat-saturated T2-weighted images were present in all patients. Median Ktrans (0.091 vs 0.000 min-1) and Kep (0.258 vs 0.000 min-1) were significantly higher within subchondral BMLs compared to surrounding subchondral bone without BMLs (p < 0.001). CONCLUSIONS: Increased perfusion parameters in epimetaphyseal bone, subchondral bone and BMLs are observed in unicompartmental knee OA. BMLs likely account for most of the effect of the higher bone perfusion in knee OA.

The effectiveness of high molecular weight hyaluronic acid for knee osteoarthritis in patients in the working age: a randomised controlled trial.

BACKGROUND: High molecular weight (HMW) hyaluronic acid (HA) is a treatment option for knee osteoarthritis (OA). The efficacy of HMW-HA in knee OA is investigated extensively, but the effectiveness in patients in the working age is unknown. Nevertheless, the number knee OA patients in the working age is increasing. Surgical treatment options are less eligible in these patients and productivity losses are high. In this study the effectiveness of intra-articular HMW-HA added to regular non-surgical usual care in everyday clinical practice (UC) compared to UC over 52 weeks in symptomatic knee OA patients in the working age was investigated. METHODS: In this open labelled randomized controlled trial, subjects aged between 18 and 65 years with symptomatic knee OA (Kellgren and Lawrence I-III) were enrolled and randomized to UC + 3 weekly injections with HMW-HA (intervention) or UC only (control). The primary outcome was the between group difference in responders to therapy according to OMERACT-OARSI criteria after 52 weeks. These criteria include the domains pain, knee related function and patient's global assessment (PGA). Function was evaluated with the KOOS questionnaire. Pain was assessed with the Numeric Rating Scale. Secondary outcome comprised the between group difference on the individual responder domains, as analysed with a random effects model. Odds Ratios (OR) were calculated by logistic regression analysis. Sensitivity analyses were performed. RESULTS: In total, 156 subjects were included (intervention group 77, control group 79). Subjects in the intervention group (HMW-HA + UC) were more often responder compared to the controls (UC). Depending on whether pain during rest or pain during activity was included in the responder domains, 57.1% versus 34.2% (p = 0.006) and 54.5% versus 34.2% (p = 0.015) was responder to therapy respectively. The results of the secondary outcome analyses show that scores on individual responder domains over all follow-up moments were statistically significant in favour of the intervention group in the domains pain during rest (δ 0.8, 95%CI 0.2; 1.4, p = 0.010), knee related function (δ - 6.8, 95%CI -11.9; - 1.7, p = 0.010) and PGA (δ - 0.7, 95%CI -0.9; - 0.4, p < 0.0001). CONCLUSIONS: Intra-articular HMW-HA added to usual care is effective for knee OA in patients in the working age. TRIAL REGISTRATION: www.trialregister.nl , NTR1651, registered 2009-3-3.

Quality of life and health status after Girdlestone resection arthroplasty in patients with an infected total hip prosthesis.

Introduction: The Girdlestone resection arthroplasty (GRA) is a salvage procedure for a recurrent or persistent prosthetic joint infection of the hip. This procedure negatively impacts the functional outcome and presumably also diminishes health status (HS) and quality of life (QOL). However, studies investigating the QOL after GRA are lacking. This cross-sectional study compares patients with a Girdlestone situation after an infected total hip prosthesis with a normative population with regard to HS and QOL. Methods: Patients with a permanent GRA were suitable to be enrolled in the study. Subjects completed the World Health Organization Quality of life (WHOQOL-BREF) and the EuroQol 5 dimension 3 level version (EQ-5D-3L). Scores were compared with data from the normal population, from patients with a lower limb amputations and data from patients with a myocardial infarction. Results: Sixty-three patients who underwent GRA between January 2000 and March 2017 completed the questionnaire. The median time between the GRA and competing the questionnaire was 48 months (4 -436). All WHOQOL-BREF domain scores were significantly lower in GRA patients compared to the normative data (p<0.001), patients with myocardial infarction or lower limb amputation. EQ-5D-3L results showed that HS was significantly impaired in GRA patients when compared to normative data (p<0.001) and also impaired when compared to data from lower limb amputations and myocardial infarctions. Conclusion: HS and QOL scores in patients with a permanent Girdlestone situation after an infected hip prosthesis are significantly lower than Dutch normative scores. Patients with a permanent Girdlestone situation scored even lower on HS than patients with a lower limb amputation or a myocardial infarction.

Bone Marrow-Harvesting Technique Influences Functional Heterogeneity of Mesenchymal Stem/Stromal Cells and Cartilage Regeneration.

BACKGROUND: Connective tissue progenitors (CTPs) from native bone marrow (BM) or their culture-expanded progeny, often referred to as mesenchymal stem/stromal cells, represents a promising strategy for treatment of cartilage injuries. But the cartilage regeneration capacity of these cells remains unpredictable because of cell heterogeneity. HYPOTHESIS: The harvest technique of BM may highly influence stem cell heterogeneity and, thus, cartilage formation because these cells have distinct spatial localization within BM from the same bone. STUDY DESIGN: Controlled laboratory study. METHODS: CTPs obtained from the femur of patients undergoing total hip replacement by 2 harvest techniques-BM aspiration and BM collection-after bone rasping were immunophenotyped by flow cytometry and evaluated for chondrogenic ability. The spatial localization of different CTP subsets in BM was verified by immunohistochemistry. RESULTS: Cells from the BM after rasping were significantly more chondrogenic than the donor-matched aspirate, whereas no notable difference in their osteogenic or adipogenic potential was observed. The authors then assessed whether distinct immunophenotypically defined CTP subsets were responsible for the different chondrogenic capacity. Cells directly isolated from BM after rasping contained a higher percentage (mean, 7.2-fold) of CD45-CD271+CD56+ CTPs as compared with BM aspirates. The presence of this subset in the harvested BM strongly correlated with chondrogenic ability, showing that CD271+CD56+ cells are enriched in chondroprogenitors. Furthermore, evaluation of these CTP subsets in BM revealed that CD271+CD56+ cells were localized in the bone-lining regions whereas CD271+CD56- cells were found in the perivascular regions. Since the iliac crest remains a frequent site of BM harvest for musculoskeletal regeneration, the authors also compared the spatial distribution of these subsets in trabeculae of femoral head and iliac crest and found CD271+CD56+ bone-lining cells in both tissues. CONCLUSION: Chondrogenically distinct CTP subsets have distinct spatial localization in BM; hence, the harvest technique of BM determines the efficiency of cartilage formation. CLINICAL RELEVANCE: The harvest technique of BM may be of major importance in determining the clinical success of BM mesenchymal stem/stromal cells in cartilage repair.

Pre-Treatment of Human Mesenchymal Stem Cells With Inflammatory Factors or Hypoxia Does Not Influence Migration to Osteoarthritic Cartilage and Synovium.

BACKGROUND: Mesenchymal stem cells (MSCs) are promising candidates as a cell-based therapy for osteoarthritis (OA), although current results are modest. Pre-treatment of MSCs before application might improve their therapeutic efficacy. HYPOTHESIS: Pre-treatment of MSCs with inflammatory factors or hypoxia will improve their migration and adhesion capacities toward OA-affected tissues. STUDY DESIGN: Controlled laboratory study. METHODS: We used real-time polymerase chain reaction to determine the effects of different fetal calf serum (FCS) batches, platelet lysate (PL), hypoxia, inflammatory factors, factors secreted by OA tissues, and OA synovial fluid (SF) on the expression of 12 genes encoding chemokine or adhesion receptors. Migration of MSCs toward factors secreted by OA tissues was studied in vitro, and attachment of injected MSCs was evaluated in vivo in healthy and OA knees of male Wistar rats. RESULTS: Different FCS batches, PL, or hypoxia did not influence the expression of the migration and adhesion receptor genes. Exposure to inflammatory factors altered the expression of CCR1, CCR4, CD44, PDGFRα, and PDGFRß. MSCs migrated toward factors secreted by OA tissues in vitro. Neither pre-treatment with inflammatory factors nor the presence of OA influenced MSC migration in vitro or adhesion in vivo. CONCLUSION: Factors secreted by OA tissues increase MSC migration in vitro. In vivo, no difference in MSC adhesion was found between OA and healthy knees. Pre-treatment with inflammatory factors influenced the expression of migration and adhesion receptors of MSCs but not their migration in vitro or adhesion in vivo. CLINICAL RELEVANCE: To improve the therapeutic capacity of intra-articular injection of MSCs, they need to remain intra-articular for a longer period of time. Pre-treatment of MSCs with hypoxia or inflammatory factors did not increase the migration or adhesion capacity of MSCs and will therefore not likely prolong their intra-articular longevity. Alternative approaches to prolong the intra-articular presence of MSCs should be developed to increase the therapeutic effect of MSCs in OA.

High fat diet accelerates cartilage repair in DBA/1 mice.

Obesity is a well-known risk factor for osteoarthritis, but it is unknown what it does on cartilage repair. Here we investigated whether a high fat diet (HFD) influences cartilage repair in a mouse model of cartilage repair. We fed DBA/1 mice control or HFD (60% energy from fat). After 2 weeks, a full thickness cartilage defect was made in the trochlear groove. Mice were sacrificed, 1, 8, and 24 weeks after operation. Cartilage repair was evaluated on histology. Serum glucose, insulin and amyloid A were measured 24 h before operation and at endpoints. Immunohistochemical staining was performed on synovium and adipose tissue to evaluate macrophage infiltration and phenotype. One week after operation, mice on HFD had defect filling with fibroblast-like cells and more cartilage repair as indicated by a lower Pineda score. After 8 weeks, mice on a HFD still had a lower Pineda score. After 24 weeks, no mice had complete cartilage repair and we did not detect a significant difference in cartilage repair between diets. Bodyweight was increased by HFD, whereas serum glucose, amyloid A and insulin were not influenced. Macrophage infiltration and phenotype in adipose tissue and synovium were not influenced by HFD. In contrast to common wisdom, HFD accelerated intrinsic cartilage repair in DBA/1 mice on the short term. Resistance to HFD induced inflammatory and metabolic changes could be associated with accelerated cartilage repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1258-1264, 2017.

Is T1ρ Mapping an Alternative to Delayed Gadolinium-enhanced MR Imaging of Cartilage in the Assessment of Sulphated Glycosaminoglycan Content in Human Osteoarthritic Knees? An in Vivo Validation Study.

PURPOSE: To determine if T1ρ mapping can be used as an alternative to delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in the quantification of cartilage biochemical composition in vivo in human knees with osteoarthritis. MATERIALS AND METHODS: This study was approved by the institutional review board. Written informed consent was obtained from all participants. Twelve patients with knee osteoarthritis underwent dGEMRIC and T1ρ mapping at 3.0 T before undergoing total knee replacement. Outcomes of dGEMRIC and T1ρ mapping were calculated in six cartilage regions of interest. Femoral and tibial cartilages were harvested during total knee replacement. Cartilage sulphated glycosaminoglycan (sGAG) and collagen content were assessed with dimethylmethylene blue and hydroxyproline assays, respectively. A four-dimensional multivariate mixed-effects model was used to simultaneously assess the correlation between outcomes of dGEMRIC and T1ρ mapping and the sGAG and collagen content of the articular cartilage. RESULTS: T1 relaxation times at dGEMRIC showed strong correlation with cartilage sGAG content (r = 0.73; 95% credibility interval [CI] = 0.60, 0.83) and weak correlation with cartilage collagen content (r = 0.40; 95% CI: 0.18, 0.58). T1ρ relaxation times did not correlate with cartilage sGAG content (r = 0.04; 95% CI: -0.21, 0.28) or collagen content (r = -0.05; 95% CI = -0.31, 0.20). CONCLUSION: dGEMRIC can help accurately measure cartilage sGAG content in vivo in patients with knee osteoarthritis, whereas T1ρ mapping does not appear suitable for this purpose. Although the technique is not completely sGAG specific and requires a contrast agent, dGEMRIC is a validated and robust method for quantifying cartilage sGAG content in human osteoarthritis subjects in clinical research.

Delayed gadolinium-enhanced MRI of the meniscus (dGEMRIM) in patients with knee osteoarthritis: relation with meniscal degeneration on conventional MRI, reproducibility, and correlation with dGEMRIC.

OBJECTIVES: To assess (1) whether normal and degenerated menisci exhibit different T1GD on delayed gadolinium-enhanced MRI of the meniscus (dGEMRIM), (2) the reproducibility of dGEMRIM and (3) the correlation between meniscus and cartilage T1GD in knee osteoarthritis (OA) patients. METHODS: In 17 OA patients who underwent dGEMRIM twice within 7 days, meniscus and cartilage T1GD was calculated. Meniscus pathology was evaluated on conventional MRI. T1GD in normal and degenerated menisci were compared using a Student's t-test. Reproducibility was assessed using ICCs. Pearson's correlation was calculated between meniscus and cartilage T1GD. RESULTS: A trend towards lower T1GD in degenerated menisci (mean: 402 ms; 95% CI: 359-444 ms) compared to normal menisci (mean: 448 ms; 95% CI: 423-473 ms) was observed (p = 0.05). Meniscus T1GD ICCs were 0.85-0.90. The correlation between meniscus and cartilage T1GD was moderate in the lateral (r = 0.52-0.75) and strong in the medial compartment (r = 0.78-0.94). CONCLUSIONS: Our results show that degenerated menisci have a clear trend towards lower T1GD compared to normal menisci. Since these results are highly reproducible, meniscus degeneration may be assessed within one delayed gadolinium-enhanced MRI simultaneously with cartilage. The strong correlation between meniscus and cartilage T1GD suggests concomitant degeneration in both tissues in OA, but also suggests that dGEMRIC may not be regarded entirely as sulphated glycosaminoglycan specific. KEY POINTS: dGEMRIM T1 GD can possibly be used to assess meniscal degeneration; dGEMRIM yields highly reproducible meniscal T1 GD in early stage osteoarthritic patients; Concomitant degeneration of cartilage and meniscus tissue occurs in early stage osteoarthritis; dGEMRIC cannot be regarded as entirely sulphated glycosaminoglycan specific.

Is anesthetic hip joint injection useful in diagnosing hip osteoarthritis? A meta-analysis of case series.

To assess the diagnostic value of intra-articular anesthetic hip injection in patients with hip pain atypical for osteoarthritis (OA), literature was searched. Included were studies assessing the diagnostic value of anesthetic hip injections in differentiating between pain caused by OA or another source. Pooled estimates of sensitivity and specificity with 95% confidence intervals (CI) were calculated. Of the 1387 potentially eligible articles, nine case series with high risk of bias could be included. The pooled sensitivity was 0.97 (95% CI 0.87, 0.99). Specificity was 0.91 (95% CI 0.83, 0.95). For clinical practice, no recommendation can be made regarding the use of hip injections for diagnosing hip OA. High quality, accurately reported studies are needed to provide better evidence on the diagnostic role of hip injection.

Associations between weather conditions and clinical symptoms in patients with hip osteoarthritis: a 2-year cohort study.

The goal of this study was to assess whether there is an association between ambient weather conditions and patients' clinical symptoms in patients with hip osteoarthritis (OA). The design was a cohort study with a 2-year follow-up and 3-monthly measurements and prospectively collected data on weather variables. The study population consisted of 222 primary care patients with hip OA. Weather variables included temperature, wind speed, total amount of sun hours, precipitation, barometric pressure, and relative humidity. The primary outcomes were severity of hip pain and hip disability as measured with the Western Ontario and McMasters University Osteoarthritis Index (WOMAC) pain and function subscales. Associations between hip pain and hip disability and the weather variables were assessed using crude and multivariate adjusted linear mixed-model analysis for repeated measurements. On the day of questionnaire completion, mean relative humidity was associated with WOMAC pain (estimate 0.1; 95% confidence interval=0.0-0.2; P=.02). Relative humidity contributed < or = 1% to the explained within-patient variance and between-patient variance of the WOMAC pain score. Mean barometric pressure was associated with WOMAC function (estimate 0.1; 95% confidence interval=0.0-0.1; P=.02). Barometric pressure contributed < or = 1% to the explained within-patient variance and between-patient variance of the WOMAC function score. The other weather variables were not associated with the WOMAC pain or function score. Our results support the general opinion of OA patients that barometric pressure and relative humidity influence perceived OA symptoms. However, the contribution of these weather variables (< or = 1%) to the severity of OA symptoms is not considered to be clinically relevant.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) shows no change in cartilage structural composition after viscosupplementation in patients with early-stage knee osteoarthritis.

INTRODUCTION: Viscosupplementation with hyaluronic acid (HA) of osteoarthritic (OA) knee joints has a well-established positive effect on clinical symptoms. This effect, however, is only temporary and the working mechanism of HA injections is not clear. It was suggested that HA might have disease modifying properties because of its beneficial effect on cartilage sulphated glycosaminoglycan (sGAG) content. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a highly reproducible, non-invasive surrogate measure for sGAG content and hence composition of cartilage. The aim of this study was to assess whether improvement in cartilage structural composition is detected using dGEMRIC 14 weeks after 3 weekly injections with HA in patients with early-stage knee OA. METHODS: In 20 early-stage knee OA patients (KLG I-II), 3D dGEMRIC at 3T was acquired before and 14 weeks after 3 weekly injections with HA. To evaluate patient symptoms, the knee injury and osteoarthritis outcome score (KOOS) and a numeric rating scale (NRS) for pain were recorded. To evaluate cartilage composition, six cartilage regions in the knee were analyzed on dGEMRIC. Outcomes of dGEMRIC, KOOS and NRS before and after HA were compared using paired t-testing. Since we performed multiple t-tests, we applied a Bonferroni-Holm correction to determine statistical significance for these analyses. RESULTS: All KOOS subscales ('pain', 'symptoms', 'daily activities', 'sports' and 'quality of life') and the NRS pain improved significantly 14 weeks after Viscosupplementation with HA. Outcomes of dGEMRIC did not change significantly after HA compared to baseline in any of the cartilage regions analyzed in the knee. CONCLUSIONS: Our results confirm previous findings reported in the literature, showing persisting improvement in symptomatic outcome measures in early-stage knee OA patients 14 weeks after Viscosupplementation. Outcomes of dGEMRIC, however, did not change after Viscosupplementation, indicating no change in cartilage structural composition as an explanation for the improvement of clinical symptoms.

Disk degeneration of the upper lumbar disks is associated with hip pain.

PURPOSE: A possible cause of hip pain is the presence of radiating pain from the higher lumbar spine. Identification of factors associated with hip pain arising from the lumbar spine would aid the physician. The first step in identifying possible factors is to look at the association between hip pain and osteoarthritis of the lumbar spine. METHODS: In an open population based study of people 55 years and older (Rotterdam study), 2,819 lumbar radiographs were scored for the presence and severity of individual radiographic features of disk degeneration. Hip osteoarthritis was scored on anteroposterior pelvic radiographs, and questionnaires including self-reported hip pain were taken. Logistic regression adjusted for possible confounders was used to determine the association between self-reported hip pain and the individual radiographic features of lumbar disk degeneration. RESULTS: The presence of dis space narrowing grade ≥1 at level L1/L2 was significantly associated with hip pain in the last month (men OR = 2.0; 95 % CI 1.1-3.8 and women OR = 1.7; 95 % CI 1.1-2.5). The presence of disk space narrowing grade ≥1 at level L2/L3 was only significantly associated with hip pain in women. The strength of the associations increased for self-reported chronic hip pain, especially in men (L1/L2 OR = 2.5; 95 % CI 1.3-5.0). The presence of disk space narrowing at the lower levels (L3/L4/L5/S1) was not significantly associated with hip pain. CONCLUSION: Our data provide evidence for an association between hip pain and disk space narrowing at disk level L1/L2 and L2/L3. In case of uncertainty of the cause of hip pain, evaluation of lumbar radiographs may help to identify those hip pain patients who might have pain arising from the lumbar spine.

Effect of Arthritic Synovial Fluids on the Expression of Immunomodulatory Factors by Mesenchymal Stem Cells: An Explorative in vitro Study.

BACKGROUND: In diseased joints, the catabolic environment results in progressive joint damage. Mesenchymal stem cells (MSCs) can have immunomodulatory effects by secreting anti-inflammatory factors. To exert these effects, MSCs need to be triggered by pro-inflammatory cytokines. To explore the potential of MSCs as a treatment for diseased joints, we studied the effect of synovial fluid (SF) from donors with different joint diseases and donors without joint pathology on the immunomodulatory capacities of human MSCs in vitro. We hypothesized that SF of diseased joints influences the immunomodulatory effects of MSCs. MATERIALS AND METHODS: MSCs were cultured in medium with SF of six osteoarthritis (OA) or six rheumatoid arthritis (RA) donors and three donors without joint pathology were used as control. Gene expressions of IL-6, HGF, TNFa, TGFb1, and indoleamine 2,3-dioxygenase (IDO) were analyzed. l-kynurenine concentration in conditioned medium (CM) by MSCs with SF was determined as a measure of IDO activity by MSCs. Furthermore, the effect of CM with SF on proliferation of activated lymphocytes was analyzed. RESULTS: Addition of SF significantly up-regulated the mRNA expression of IL-6 and IDO in MSCs. SF(OA) induced significantly higher expression of IDO than SF(control), although no difference in IDO activity of the MSCs could be shown with a l-kynurenine assay. Medium conditioned by MSCs with SF(OA or RA) suppressed activated lymphocyte proliferation in vitro more than medium conditioned by MSCs without SF or with SF(control). DISCUSSION: SF can influence the expression of genes involved in immunomodulation by MSCs and the effect on lymphocyte proliferation. We found indications for disease-specific differences between SFs but the variation between donors, even within one disease group was high. These data warrant further research to examine the potential application of MSC therapy in arthritic joints.

Survival of short hip stems with a "modern", trochanter-sparing design - a systematic literature review.

Modern total hip arthroplasty delivers excellent and reproducible results. New implant developments include a wide range of implants with a bone and tissue sparing design, including short femoral stems. This review was performed to provide an overview on the currently published survival results of short stems to allow comparison with the results of traditional hip stems. A literature search was performed to identify publications on short stems with a "modern" trochanter sparing design including implant survival information. Information was collected on the study population, follow-up time, implants used, implant survival and functional scores. The revision rate per 100 observed component years was calculated and compared to data presented in national arthroplasty registries. The methodological quality was assessed by employing a score specific to survival assessment of hip stems. In the course of 16 individual searches in EMBASE and Medline, 460 potentially eligible articles were identified. After thorough screening, 14 articles were deemed applicable. The variability in quality of the publications was high. No association between survival outcome and publication quality was apparent. The total revision rate over all studies was found to be 0.38 per 100 component years with endpoint "stem revision for any reason". The survival rate of these stems is encouraging and appears to be comparable with that of more traditional uncemented stems. However, only few mid-term and long-term studies are available. Reports with longer follow-up are needed to draw further conclusions.

Phenotypic spectrum of the SMAD3-related aneurysms-osteoarthritis syndrome.

BACKGROUND: Aneurysms-osteoarthritis syndrome (AOS) is a new autosomal dominant syndromic form of thoracic aortic aneurysms and dissections characterised by the presence of arterial aneurysms and tortuosity, mild craniofacial, skeletal and cutaneous anomalies, and early-onset osteoarthritis. AOS is caused by mutations in the SMAD3 gene. METHODS: A cohort of 393 patients with aneurysms without mutation in FBN1, TGFBR1 and TGFBR2 was screened for mutations in SMAD3. The patients originated from The Netherlands, Belgium, Switzerland and USA. The clinical phenotype in a total of 45 patients from eight different AOS families with eight different SMAD3 mutations is described. In all patients with a SMAD3 mutation, clinical records were reviewed and extensive genetic, cardiovascular and orthopaedic examinations were performed. RESULTS: Five novel SMAD3 mutations (one nonsense, two missense and two frame-shift mutations) were identified in five new AOS families. A follow-up description of the three families with a SMAD3 mutation previously described by the authors was included. In the majority of patients, early-onset joint abnormalities, including osteoarthritis and osteochondritis dissecans, were the initial symptom for which medical advice was sought. Cardiovascular abnormalities were present in almost 90% of patients, and involved mainly aortic aneurysms and dissections. Aneurysms and tortuosity were found in the aorta and other arteries throughout the body, including intracranial arteries. Of the patients who first presented with joint abnormalities, 20% died suddenly from aortic dissection. The presence of mild craniofacial abnormalities including hypertelorism and abnormal uvula may aid the recognition of this syndrome. CONCLUSION: The authors provide further insight into the phenotype of AOS with SMAD3 mutations, and present recommendations for a clinical work-up.