Hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in cartilage tumors.

Neoangiogenesis has been demonstrated in chondrosarcoma. Anti-angiogenic therapies are being tested in clinical trials for chondrosarcomas. Studies of the underlying mechanisms have been performed almost exclusively in cell lines. We immunostained 20 samples of chondrosarcoma and 20 samples of enchondromas with antibodies against hypoxia-inducible factor 1-alpha (HIF-1-alpha) and vascular endothelial growth factor (VEGF). The immunohistochemical staining of HIF-1-alpha and VEGF were highly correlated. Enchondromas were HIF-1-alpha and VEGF negative, whereas all chondrosarcoma exhibited HIF-1-alpha and VEGF immunostaining. HIF-1-alpha/VEGF double positive cases were almost exclusively chondrosarcomas with a high tumor grade. We suggest that HIF-1-alpha is a marker of malignancy in chondrosarcomas that correlates with tumor neo-angiogenesis. Our findings also suggest that a HIF-1-alpha/VEGF angiogenic pathway may exist in chondrosarcoma in vivo as in other malignant tumors. The inclusion of novel inhibitors to HIF-1-alpha and other factors may optimize anti-angiogenic interventions in chondrosarcoma.

Treatment outcomes for infected juxta-articular knee nonunions.

PURPOSE: This retrospective case series assessed the results of a treatment protocol for patients with infected para-articular knee nonunions. The aim was to demonstrate that knee function and quality-of-life (QoL) can be improved. CASE SERIES: Between January 2001 and December 2011, eleven patients with septic proximal tibial nonunion and seven with septic distal femoral nonunion were managed at our institution. The treatment protocol included extensive debridement, skeletal stabilization, culture-specific antibiotic administration, and soft-tissue and bone-deficit reconstruction. Knee function was evaluated with the Knee Society Score (KSS) while the Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-12 were used for QoL assessment at a mean follow-up of 37.2 (range: 12-149) months. Seventeen nonunions healed at a mean of 21.9 weeks. One patient needed above knee amputation. Knee Society function and knee scores were improved significantly, from 16.7 and 33.8, to 75.0 and 84.9 respectively (p <0.001). KOOS outcome and SF-12 physical and mental components scores confirmed the QoL improvement. CONCLUSIONS: Staged management can improve QoL and functional knee outcome. HIPPOKRATIA 2018, 22(4): 183-187.

Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes.

BACKGROUND: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study, we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in the serum as potential OA biomarkers. METHODS: Serum samples were collected from 12 primary OA patients, and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative real-time PCR (qRT-PCR) in all serum and in articular cartilage samples from OA patients (n = 12) and healthy individuals (n = 7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs. RESULTS: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to controls. Two hundred and five miRNAs (73.5%) were upregulated and 74 (26.5%) downregulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC) > 0.8 and p < 0.05. Bioinformatics analysis in the 77 miRNAs revealed that their target genes were involved in multiple signaling pathways associated with OA, among which FoxO, mTOR, Wnt, pI3K/akt, TGF-ß signaling pathways, ECM-receptor interaction, and fatty acid biosynthesis. qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. CONCLUSIONS: A serum miRNA signature was established for the first time using high density resolution miR-arrays in OA patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, in the serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression.

Articular cartilage status 2 years after arthroscopic ACL reconstruction in patients with or without concomitant meniscal surgery: evaluation with 3.0T MR imaging.

PURPOSE: To assess articular cartilage changes in the knee joint as detected on 3.0T MR imaging after 2-year follow-up in patients who underwent arthroscopic anterior cruciate ligament reconstruction (ACLR) with or without concomitant meniscal surgery. METHODS: A total of twenty-nine patients (mean age 30.3 ± 10 years), who underwent arthroscopic ACLR, received clinical and imaging follow-up at an average of 27.8 ± 4.8 months after surgery. Our patients were divided into two subgroups: eighteen patients with additional meniscal injuries at the time of arthroscopic ACLR who underwent meniscal surgery and eleven patients with intact menisci. The cartilage status of all knees at the time of arthroscopic ACLR was recorded. All patients underwent an MRI scan preoperatively and at follow-up with the same imaging protocol. Cartilage status of all knee compartments was evaluated at the time of follow-up by MR imaging and the ICRS classification. RESULTS: Deterioration of the cartilage status was found at all knee compartments of our study group, with respect to the number of cartilage defects. The cartilage of the lateral femoral condyle (LFC) was most severely affected, followed by patellar and medial femoral condyle (MFC) cartilage. A statistically significant relation was found between surgery of the medial meniscus and the development of new cartilage defects in LFC (p = 0.01) and MFC (p = 0.03) after adjusting for the site of meniscal surgery. The cartilage of LFC and the status of the medial meniscus were also found to be significantly related (p = 0.04). Partial meniscectomy was found to be associated with an increased incidence of new cartilage defects when compared to either meniscal repair or absence of meniscal surgery, although it was not statistically significant. CONCLUSION: Development of new cartilage lesions was evident after 2-year follow-up in patients with arthroscopic ACLR as detected by MR imaging. There was a multicompartmental pattern of cartilage involvement, and the lateral compartment was most severely affected. Partial meniscectomy at the time of arthroscopic ACLR could be suggested as an additional risk factor for the progression of chondral lesions. LEVEL OF EVIDENCE: Prospective comparative study, Level II.

Histological and biochemical evidence related to the collagen quality in torn rotator cuff tendons.

This study investigates the histological background of torn rotator cuff tendons, evaluates the stability of newly synthesized collagen by measuring the hydro-xyproline content and attempts to correlate these findings with the clinical outcome after reconstruction of the rotator cuff. Sixty-one patients underwent reconstruction for a -rotator cuff tear. They were evaluated preoperatively with the Constant-Murley score, MRI and ultrasound. Biopsy samples were taken from chronic rotator cuff tears and histological analysis was performed. Hydroxyprolin presence was evaluated in various -tissues. Mean follow-up was 46 months. Histological analysis revealed collagen fragmentation and thinning (90.2% of patients), myxoid degeneration (88%), hyaline degeneration (50.8%), chondroid metaplasia (44.3%), calcification (24.7%), fatty infiltration (20.4%) and vascular proliferation (62.3%). Hydroxyproline was under-represented in newly synthesized collagen in 57% of patients. In the majority of the patients with a low hydroxyproline/collagen ratio the histological findings were abnormal. None of the findings was related to the clinical outcome with a statistical significance. Histological and biochemical findings reflected the poor quality of the tendon. The good clinical outcome did not depend on the histological or biochemical findings but rather on the meticulous surgical reconstruction and physical therapy.

Non-Metastatic Pelvic Ewing's Sarcoma : oncologic outcomes and evaluation of prognostic factors.

We are reporting our experience on patients with -pelvic Ewing's Sarcoma treated in our unit. We retrospectively reviewed a series of patients with non-metastatic pelvic Ewing's sarcoma treated between 1977 and 2009. Patients were classified into three groups according to the local treatment received : Group 1. radiotherapy-chemo ; Group 2. surgery-chemo and Group 3. radiotherapy-surgery-chemo. Recurrence free and overall survival rates were calculated using the Kaplan-Meier method. Influence of various factors (age at diagnosis, gender, tumour site and size, chemotherapy response, surgical margins and type of treatment) on survival was assessed with a logistic regression model. A total of 85 patients were treated with a mean follow-up of 65.8 months and mean -tumour volume of 435ml. The 5-year survival for all patients was 40.7% decreased to 36.2% at 10 years. A significant prognostic factor identified was chemotherapy response only. There was a trend for improved survival and local control rates for patients who had chemotherapy and surgery and the results were apparent for all tumours irrespective of size but not statistically significant. Currently, the optimal management of pelvic Ewing's sarcoma is contro-versial but our study shows a trend for improved -survival for patients treated with chemotherapy and surgery.

An 11- to 15-year clinical outcome study of the Advance Medial Pivot total knee arthroplasty: pivot knee arthroplasty.

AIMS: The Advance Medial-Pivot total knee arthroplasty (TKA) was designed to reflect contemporary data regarding the kinematics of the knee. We wished to examine the long-term results obtained with this prosthesis by extending a previous evaluation. PATIENTS AND METHODS: We retrospectively evaluated prospectively collected data from 225 consecutive patients (41 men and 184 women; mean age at surgery 71 years, 52 to 84) who underwent 284 TKAs with a mean follow-up of 13.4 years (11 to 15). Implant failure, complication rate, clinical (both subjective and objective) and radiological outcome were assessed. Pre- and post-operative clinical and radiographic data were available at regular intervals for all patients. A total of ten patients (4.4%; ten TKAs) were lost to follow-up. RESULTS: Survival analysis at 15 years showed a cumulative success rate of 97.3% (95% confidence interval (CI) 96.7 to 97.9) for revision for any reason, of 96.4% (95% CI 95.2 to 97.6) for all operations, and 98.8% (95% CI 98.2 to 99.4) for aseptic loosening as an end point. Three TKAs (1.06%) were revised due to aseptic loosening, two (0.7%) due to infection, one (0.35%) due to instability and one (0.35%) due to a traumatic dislocation. All patients showed a statistically significant improvement on the Knee Society Score (p = 0.001), Western Ontario and McMaster University Osteoarthritis Index (p = 0.001), Short Form-12 (p = 0.01), and Oxford Knee Score (p = 0.01). A total of 207 patients (92%) were able to perform age appropriate activities with a mean flexion of the knee of 117° (85° to 135°) at final follow-up. CONCLUSION: This study demonstrates satisfactory functional and radiographic long-term results for this implant. Cite this article: Bone Joint J 2016;98-B:1050-5.

Daptomycin for the treatment of osteomyelitis and orthopaedic device infections: real-world clinical experience from a European registry.

Osteomyelitis is a serious infection predominantly caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Orthopaedic device-related infections are complex and require a careful combination of surgical intervention and antimicrobial therapy. Daptomycin, a cyclic lipopeptide, effectively penetrates soft tissue and bone and demonstrates rapid concentration-dependent bactericidal activity against Gram-positive pathogens. This retrospective, non-interventional study evaluated clinical outcomes in patients with osteomyelitis or orthopaedic device infections treated with daptomycin from the European Cubicin® Outcomes Registry and Experience (EU-CORE(SM)) study. Patients were treated between January 2006 and April 2012, with follow-up to 2014. Clinical outcomes were assessed as success (cured or improved), failure or non-evaluable. Of 6,075 patients enrolled, 638 (median age, 63.5 years) had primary infections of osteomyelitis or orthopaedic device infections, 224 had non-prosthetic osteomyelitis, 208 had osteomyelitis related to a permanent or temporary prosthetic device, and 206 had orthopaedic device infections. The most commonly isolated pathogen was S. aureus (214 [49.1 %]; 24.8 % were MRSA). Overall, 455 (71.3 %) patients had received previous antibiotic therapy. Patients underwent surgical interventions, including tissue (225 [35.3 %]) and bone (196 [30.7 %]) debridement, as part of their treatment. Clinical success rates were 82.7 % and 81.7 % in S. aureus and coagulase-negative staphylococcal infections. Adverse events (AEs) and serious AEs assessed as possibly related to daptomycin were observed in 6.7 % and 1.9 % of patients, respectively. Daptomycin was discontinued by 5.5 % of patients due to AEs and 10 (1.6 %) deaths were reported. In conclusion, daptomycin was effective and safe in patients with osteomyelitis or orthopaedic device infections.

RhBMP-7 for the treatment of nonunion of fractures of long bones.

We report the outcome of 84 nonunions involving long bones which were treated with rhBMP-7, in 84 patients (60 men: 24 women) with a mean age 46 years (18 to 81) between 2003 and 2011. The patients had undergone a mean of three previous operations (one to 11) for nonunion which had been present for a mean of 17 months (4 months to 20 years). The nonunions involved the lower limb in 71 patients and the remainder involved the upper limb. A total of 30 nonunions were septic. Treatment was considered successful when the nonunion healed without additional procedures. The relationship between successful union and the time to union was investigated and various factors including age and gender, the nature of the nonunion (location, size, type, chronicity, previous procedures, infection, the condition of the soft tissues) and type of index procedure (revision of fixation, type of graft, amount of rhBMP-7) were analysed. The improvement of the patients' quality of life was estimated using the Short Form (SF) 12 score. A total of 68 nonunions (80.9%) healed with no need for further procedures at a mean of 5.4 months (3 to 10) post-operatively. Multivariate logistic regression analysis of the factors affecting union suggested that only infection significantly affected the rate of union (p = 0.004).Time to union was only affected by the number of previous failed procedures (p = 0.006). An improvement of 79% and 32.2% in SF-12 physical and mental score, respectively, was noted within the first post-operative year. Rh-BMP-7 combined with bone grafts, enabled healing of the nonunion and improved quality of life in about 80% of patients. Aseptic nonunions were much more likely to unite than septic ones. The number of previous failed operations significantly delayed the time to union.

Autologous (non-vascularised) fibular grafting with recombinant bone morphogenetic protein-7 for the treatment of femoral head osteonecrosis: preliminary report.

This preliminary study evaluates a combination of bone morphogenetic protein (BMP)-7 and non-vascularised autologous fibular grafting (AFG) for the treatment of osteonecrosis of the femoral head. BMP-7/AFG combination was applied in seven pre-collapse femoral heads (five Steinberg stage II, two stage III) in six patients. Pre- and post-operative evaluation included clinical (Harris hip score (HHS), visual analogue scale (VAS) for pain) and radiological assessment (radiographs, quantitative CT) at a mean follow-up of 4 years (2 to 5.5). A marked improvement of function (mean HHS increase of 49.2) and decrease of pain level (mean VAS decrease of 5) as well as retention of the sphericity of the femoral head was noted in five hips at the latest follow-up, while signs of consolidation were apparent from the third post-operative month. One patient (two hips) required bilateral total hip replacement at one year post-operatively. In the series as a whole, quantitative-CT evaluation revealed similar densities between affected and normal bone. Heterotopic ossification was observed in four hips, without compromise of the clinical outcome. In this limited series AFG/BMP-7 combination proved a safe and effective method for the treatment of femoral head osteonecrosis, leading to early consolidation of the AFG and preventing collapse in five of seven hips, while the operative time and post-operative rehabilitation period were much shorter compared with free vascularised fibular grafts.

Acute calcific tendinitis of the longus colli muscle: case report and review of the literature.

PURPOSE: Acute calcific tendinitis of the longus colli muscle (or retropharyngeal tendinitis) is an aseptic inflammatory process characterized by acute posterior neck pain, neck stiffness and dysphagia or odynophagia. Awareness of its existence is crucial in the differential diagnosis, because many other conditions, such as retropharyngeal abscess, meningitis or disc herniation, show similar clinical features. We present a case exhibiting an uncommon symptom (torticollis) and a brief literature review to emphasize the risk of misdiagnosis. METHODS: A 36-year-old woman presented with neck stiffness and torticollis accompanied by dysphagia and prevertebral space sensitivity on the second day. RESULTS: The diagnosis was established by computed tomography (CT), the gold standard for identifying the presence of prevertebral oedema and calcific deposition associated with retropharyngeal tendinitis. Treatment with NSAIDs and low doses of corticosteroids relieved the symptoms within 48 h. CONCLUSIONS: Retropharyngeal tendinitis is an underreported entity in the literature and orthopaedists should become aware of its existence. Misdiagnosis of this important mimicker may lead to unnecessary antibiotics administration and interventions in the retropharyngeal space.

Smoking affects mRNA expression of bone morphogenetic proteins in human periosteum.

Periosteum is important for bone homoeostasis through the release of bone morphogenetic proteins (BMPs) and their effect on osteoprogenitor cells. Smoking has an adverse effect on fracture healing and bone regeneration. The aim of this study was to evaluate the effect of smoking on the expression of the BMPs of human periosteum. Real-time polymerase chain reaction was performed for BMP-2,-4,-6,-7 gene expression in periosteal samples obtained from 45 fractured bones (19 smokers, 26 non-smokers) and 60 non-fractured bones (21 smokers, 39 non-smokers). A hierarchical model of BMP gene expression (BMP-2 > BMP-6 > BMP-4 > BMP-7) was demonstrated in all samples. When smokers and non-smokers were compared, a remarkable reduction in the gene expression of BMP-2, -4 and -6 was noticed in smokers. The comparison of fracture and non-fracture groups demonstrated a higher gene expression of BMP-2, -4 and -7 in the non-fracture samples. Within the subgroups (fracture and non-fracture), BMP gene expression in smokers was either lower but without statistical significance in the majority of BMPs, or similar to that in non-smokers with regard to BMP-4 in fracture and BMP-7 in non-fracture samples. In smokers, BMP gene expression of human periosteum was reduced, demonstrating the effect of smoking at the molecular level by reduction of mRNA transcription of periosteal BMPs. Among the BMPs studied, BMP-2 gene expression was significantly higher, highlighting its role in bone homoeostasis.

Predictive role of cytokine gene polymorphisms for the development of femoral head osteonecrosis.

INTRODUCTION: Osteonecrosis (ON) is a multifactorial disease that leads to hip destruction. Lately, much focus has been at femoral head preservation with nonsurgical methods. In this study we examined the polymorphisms of IL-1α, IL-1R, IL-1RA, IL-4Rα, IL-1ß, IL-12, γIFN, TGF-ß, TNF-a, IL-2, IL-4, IL-6 and IL-10 genes for evaluation of their contribution in ON. MATERIAL AND METHODS: DNA was extracted from 112 ON patients and 438 healthy donors. Analysis of the polymorphisms was completed using the PCR-SSP method. Statistical analysis was performed using the χ ^{2} test to compare the genotype and allelic frequency distribution. RESULTS: The CT and GA genotypes of the IL-1α (-889) and TNF-a (-238) genes were found higher in the patients (51.8% and 10.8%, respectively) compared to the healthy donors (39.7% and 2.1%, respectively). In TGF-ß codon 25, the G to C polymorphism in the homozygous state was found in 1.8% of the patients and the C allele frequency was 8.9%, whereas the G allele frequency was 91.1%. Also, at the IL-10 (-1082) gene the GG genotype was 16.2% in the controls whereas in the patients was 7.2%. CONCLUSIONS: Based on the above, we showed that certain genotypes of the IL-1α, TGF-ß, IL-10 and TNF-a genes could be related in the pathogenesis of a complicated disease, such as osteonecrosis. The presence of one of the above mentioned polymorphisms or the simultaneous carriage of more than one may further increase the risk for osteonecrosis, especially in those at high risk, such as patients receiving corticosteroids.

Early results of a novel technique using multiple small tantalum pegs for the treatment of osteonecrosis of the femoral head: a case series involving 26 hips.

The introduction of a trabecular tantalum rod has been proposed for the management of early-stage osteonecrosis of the femoral head but serves as a single-point of support of the necrotic lesion. We describe a technique using two or three 4.2 mm (or later 4.7 mm) tantalum pegs for the prevention of collapse of the necrotic lesion. We prospectively studied 21 patients (26 hips) with non-traumatic osteonecrosis of the femoral head treated in this manner. Of these, 21 patients (24 hips) were available for radiological and clinical evaluation at a mean follow-up of 46 months (18 to 67). Radiological assessment showed that only eight hips deteriorated according to the Association Research Circulation Osseous classification, and four hips according to the Classification of the Japanese Investigation Committee of Health and Welfare. Functional improvement was obtained with an improvement in the mean Harris hip score from 65.2 (33.67 to 95) to 88.1 (51.72 to 100), the mean Merle D'Aubigné-Postel score from 13 (6 to 18) to 16 (11 to 18), a mean visual analogue score for pain from 5.2 (0 to 9.5) to 2.6 (0 to 7), and the mean Short-Form 36 score from 80.4 (56.8 to 107.1) to 92.4 (67.5 to 115.7). Of these 24 hips followed for a minimum of 18 months, three were considered as failures at the final follow-up, having required total hip replacement. One of the hips without full follow-up was also considered to be a failure. In more than two-thirds of the surviving hips a satisfactory clinical outcome was achieved with promising radiological findings. The estimated mean implant survival was 60 months (95% confidence interval 53.7 to 66.3).

Digital coverage with flaps from the same or neighboring digits.

OBJECTIVE: Several flaps can be dissected from the same or neighboring digits for the reconstruction of relatively large soft tissue digital defects. MATERIAL AND METHODS: In a 6-year period, 106 large soft tissue digital defects were reconstructed with the use of flaps in 101 patients. For the reconstruction of 75 fingertip defects 73 neurovascular, island or advancement flaps (42 homodigital, 18 heterodigital, 13 advancement) and 2 thenar flaps were used. The 31 defects of the proximal and middle phalanges were reconstructed with 3 intermetacarpal and 28 cross-finger flaps (17 de-epithelialized and 11 classic for dorsal and palmar defects respectively). RESULTS: All flaps survived. Subjectively, the results were rated as good or excellent in 69 of 73 distal defects reconstructed with neurovascular island or advancement flaps and in 29 of 31 proximal defects treated with cross-finger and intermetacarpal flaps. The mean DASH score was 4.1 and 3.34 for the neurovascular island/advancement flaps and the cross-finger flaps respectively. CONCLUSIONS: This study elucidates the indications and presents the advantages and disadvantages of flaps used for reconstruction of proximal and distal digital defects. Good results can be obtained with appropriate flap selection and meticulous surgical technique.

Complex regional pain syndrome type I as a consequence of trauma or surgery to upper extremity: management with intravenous regional anaesthesia, using lidocaine and methyloprednisolone.

Complex regional pain syndrome type I (CRPS-I) is a known complication after surgery or trauma to the upper extremity and is difficult to treat. A simple and easily tolerated method of treatment that includes intravenous regional anaesthetic block with lidocaine and methyloprednisolone is presented. One hundred and sixty-eight patients with CRPS-I of the upper extremity were treated in a 5-year period. At the end of treatment 88% of the patients reported minimal or no pain. After a mean follow-up of 5 years (range 28 months to 7 years) complete absence of pain was reported by 92% of patients. The symptoms of the acute phase of the syndrome were reversed. Early recognition and prompt initiation of treatment is very important for the course of the disease as symptoms can be reversible when treatment starts early. Permanent results with a functional upper extremity and very satisfactory pain relief can be anticipated.

Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium.

OBJECTIVE: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. METHODS: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. RESULTS: In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P =0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3×10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. CONCLUSION: Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies.

White Matter Lesions in Femoral Head Osteonecrosis patients: Manifestation of vascular disease or not?

BACKGROUND: Osteonecrosis has been associated with the presence of white matter lesions. The objective of this study was to investigate the association between macro- and micro- vascular disease and white matter lesions. METHODS: Sixty-four patients with femoral head osteonecrosis were assessed during a cross sectional study in our university-based hospital. A vascular 'profile' was obtained for each patient and included measurement of plasma lipids, fundoscopic examination and common carotid artery triplex ultrasonography. All patients had brain MRI to assess for presence of white matter lesions. The two groups formed, with and without white matter lesions, were compared in order to define the association between white matter lesions and vascular disease. RESULTS: Patients without white matter lesions had more frequently corticosteroid induced osteonecrosis. There was no difference in the two groups with respect to intima media thickness and ApoB/ApoA1 ratio. Only one of our patients demonstrated retinopathy. CONCLUSIONS: There is no evidence of concurrent macro- and micro- vascular pathology in young patients with white matter lesions and femoral head osteonecrosis. Cortisone appears to have a 'protective' effect against occurrence of white matter lesions.

Ultrasonographic evidence of inflammation is frequent in hands of patients with erosive osteoarthritis.

OBJECTIVE: Erosive osteoarthritis (OA) (EOA) is considered an aggressive form of primary OA that is defined radiographically by intra-articular erosions of the inter-phalangeal joints of the hand and characteristic deformities. The aim of the present study was the sonographic investigation of hand small joints in patients with EOA and comparison of the imaging findings with conventional radiography (CR). METHOD: Twenty-two patients (20 women, mean age 62.5 years) with clinical and radiographic diagnosis of EOA formed our study group. A total of 660 joints were assessed by both radiographs and ultrasound (US). US and plain films were evaluated by two different physicians on a blinded fashion. Erosions, osteophytes and deformities were evaluated by both US and plain films. Synovial thickening, effusion, and power Doppler signal indicative of abnormal vascularity were recorded in each joint during US scanning. RESULTS: Erosions were detected in 231/660 (35%) small joints by US and in 115/660 (17.4%) small joints by conventional radiographs (P<0.05). Osteophytes were detected in 360/660 (54.5%) small joints by US, and in 310/660 (47.0%) small joints by conventional radiographs (P<0.05). Thickened synovium was detected in 19 of 22 patients and increased intra-articular power Doppler signal, indicative of active inflammation, was detected in 18 of 22 patients. Thickened synovium was found in 159/660 (24.1%), effusion in 119/660 (18%) and increased power Doppler in 148/660 (22.4%) small joints. Intra-observer kappa value for agreement regarding US was 0.81 and plain films 0.86. In 31 instances extensive finger tenosynovitis was also evident. CONCLUSION: In patients with EOA, US is a reliable and a more sensitive imaging modality than CR in detecting erosions and osteophytes. US detects inflammatory changes in small hand joints in the vast majority of patients with EOA and suggests that current treatment modalities are inadequate treatment for this disease.

Use of a mini-external fixator for the treatment of hand fractures.

PURPOSE: To evaluate the outcome of hand fractures managed with mini-external fixators (MEFs) in order to assess their usefulness in different fracture types and to make recommendations regarding potential applications. METHODS: Fifty-one patients with 59 metacarpal and phalangeal fractures were treated with MEFs. Fixators were used to reduce the fracture or to achieve volar plate arthroplasty when anatomical joint reconstruction was impossible. The mean period from injury to MEF application was 4.5 days. RESULTS: The procedure was performed using regional anesthesia and fluoroscopic control, and it lasted 20 to 45 minutes. MEFs were removed in a mean period of 6 weeks, and follow-up was 18 to 55 months. Forty-nine patients with 57 fractures remained in the follow-up group. In all cases the skeleton was successfully reconstructed, whereas the clinical outcome varied according to the type of the original injury: intra-articular fractures had worse outcome than extra-articular (p=.035 for grip strength and p=.0005 for total active motion), and open fractures had worse outcome than closed (p=.06 for grip strength and p=.001 for total active motion). In all cases, patients' satisfaction was high; the Disabilities of the Arm, Shoulder, and Hand score was <7.9 and the visual analog scale score was <0.5. CONCLUSIONS: The findings of this series demonstrate the efficacy of versatile MEFs to establish union and correct alignment of hand skeleton with minimal tissue trauma while retaining a good clinical outcome even in the most complex injuries. MEFs can be considered for all hand fractures requiring surgical treatment, and especially for the intra-articular and comminuted fractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.