Magnetic resonance imaging of the hip at 3 Tesla: clinical value in femoroacetabular impingement of the hip and current concepts

Magnetic resonance imaging (MRI) is the most promising noninvasive modality for hip joint evaluation, but it has limitations in diagnosing cartilage lesion and acetabular labrum changes, especially in early stages. This is significant due to superior outcome results of surgery intervention in hip dysplasia or femoroacetabular impingement in patients not exceeding early degeneration. This emphasizes the need for accurate and reproducible methods in evaluating cartilage structure. In this article, we discuss the impact of the most recent technological advance in MRI, namely the advantage of 3-T imaging, on diagnostic imaging of the hip. Limitations of standard imaging techniques are shown with emphasis on femoroacetabular impingement. Clinical imaging examples and biochemical techniques are presented that need to be further evaluated.

Restorative neuroscience: concepts and perspectives

There is increasing interest in the search for therapeutic options for diseases and injuries of the central nervous system (CNS), for which currently no effective treatment strategies are available. Replacement of damaged cells and restoration of function can be accomplished by transplantation of cells derived from different sources, such as human foetal tissue, genetically modified cell lines, embryonic or somatic stem cells. Preclinical and clinical trials have shown promising results in neurodegenerative disorders, like Parkinson's and Huntington's disease, but also ischaemic stroke, intracerebral haemorrhage, demyelinating disorders, epilepsy and traumatic lesions of the brain and spinal cord. Other studies have focused on finding new ways to activate and direct endogenous repair mechanisms in the CNS, eg, by exposure to specific neuronal growth factors or by inactivating inhibitory molecules. Neuroprotective drugs may offer an additional tool for improving neuronal survival in acute or chronic CNS diseases. Importantly however, a number of scientific issues need to be addressed in order to permit the introduction of these experimental techniques in the wider clinical setting.

Cartilage damage in femoroacetabular impingement (FAI): preliminary results on comparison of standard diagnostic vs delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC)

OBJECTIVES: To study the three-dimensional (3D) T1 patterns in different types of femoroacetabular impingement (FAI) by utilizing delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and subsequent 3D T1 mapping. We used standard grading of OA by Tonnis grade on standard radiographs and morphological grading of cartilage in MRI for comparative analysis. METHODS: dGEMRIC was obtained from ten asymptomatic young-adult volunteers and 26 symptomatic FAI patients. MRI included the routine hip protocol and a dual-flip angle (FA) 3D gradient echo (GRE) sequence utilizing inline T1 measurement. Cartilage was morphologically classified from the radial images based on the extent of degeneration as: no degeneration, degeneration zone measuring <0.75 cm from the rim, >0.75 cm, or total loss. T1 findings were evaluated and correlated. RESULTS: All FAI types revealed remarkably lower T1 mean values in comparison to asymptomatic volunteers in all regions of interest. Distribution of the T1 dGEMRIC values was in accordance with the specific FAI damage pattern. In cam-types (n=6) there was a significant drop (P<0.05) of T1 in the anterior to superior location. In pincer-types (n=7), there was a generalized circumferential decrease noted. High inter-observer (intra-observer) reliability was noted for T1 assessment using intra-class correlation (ICC):intra-class coefficient=0.89 (0.95). CONCLUSIONS: We conclude that a pattern of zonal T1 variation does seem to exist that is unique for different sub-groups of FAI. The FA GRE approach to perform 3D T1 mapping has a promising role for further studies of standard MRI and dGEMRIC in the hip joint.

Doxycycline for osteoarthritis of the knee or hip

BACKGROUND: Osteoarthritis is a chronic joint disease that involves degeneration of articular cartilage. Pre-clinical data suggest that doxycycline might act as a disease-modifying agent for the treatment of osteoarthritis, with the potential to slow cartilage degeneration. OBJECTIVES: To examine the effects of doxycycline compared with placebo or no intervention on pain and function in patients with osteoarthritis of the hip or knee. SEARCH STRATEGY: We searched CENTRAL ( The Cochrane Library 2008, issue 3), MEDLINE, EMBASE and CINAHL up to 28 July 2008, checked conference proceedings, reference lists, and contacted authors. SELECTION CRITERIA: We included studies if they were randomised or quasi-randomised controlled trials that compared doxycycline at any dosage and any formulation with placebo or no intervention in patients with osteoarthritis of the knee or hip. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate. We contacted investigators to obtain missing outcome information. We calculated differences in means at follow-up between experimental and control groups for continuous outcomes and risk ratios for binary outcomes. MAIN RESULTS: We found one randomised controlled trial that compared doxycycline with placebo in 431 obese women. After 30 months of treatment, clinical outcomes were similar between the two treatment groups, with a mean difference of -0.20 cm (95% confidence interval (CI) -0.77 to 0.37 cm) on a visual analogue scale from 0 to 10 cm for pain and -1.10 units (95% CI -3.86 to 1.66) for function on the WOMAC disability subscale, which ranges from 17 to 85. These differences correspond to clinically irrelevant effect sizes of -0.08 and -0.09 standard deviation units for pain and function, respectively. The difference in changes in minimum joint space narrowing was in favour of doxycycline (-0.15 mm, 95% CI -0.28 to -0.02 mm), which corresponds to a small effect size of -0.23 standard deviation units. More patients withdrew from the doxycycline group compared with placebo due to adverse events (risk ratio 1.69, 95% CI 1.03 to 2.75). AUTHORS' CONCLUSIONS: The symptomatic benefit of doxycycline is minimal to non-existent. The small benefit in terms of joint space narrowing is of questionable clinical relevance and outweighed by safety problems. Doxycycline should not be recommended for the treatment of osteoarthritis of the knee or hip.

High resolution fast T1 mapping technique for dGEMRIC

PURPOSE: To determine the feasibility of using a high resolution isotropic three-dimensional (3D) fast T1 mapping sequence for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) to assess osteoarthritis in the hip. MATERIALS AND METHODS: T1 maps of the hip were acquired using both low and high resolution techniques following the administration of 0.2 mmol/kg Gd-DTPA(2-) in 35 patients. Both T1 maps were generated from two separate spoiled GRE images. The high resolution T1 map was reconstructed in the anatomically equivalent plane as the low resolution map. T1 values from the equivalent anatomic regions containing femoral and acetabular cartilages were measured on the low and high resolution maps and compared using regression analysis. RESULTS: In vivo T1 measurements showed a statistically significant correlation between the low and high resolution acquisitions at 1.5 Tesla (R(2) = 0.958, P < 0.001). These results demonstrate the feasibility of using a fast two-angle T1 mapping (F2T1) sequence with isotropic spatial resolution (0.8 x 0.8 x 0.8 mm) for quantitative assessment of biochemical status in articular cartilage of the hip. CONCLUSION: The high resolution 3D F2T1 sequence provides accurate T1 measurements in femoral and acetabular cartilages of the hip, which enables the biochemical assessment of articular cartilage in any plane through the joint. It is a powerful tool for researchers and clinicians to acquire high resolution data in a reasonable scan time (< 30 min).

Delayed gadolinium enhanced MRI of cartilage (dGEMRIC): Molekulare MRT-Bildgebung des Hüftgelenkknorpels [Delayed gadolinium enhanced MRI of cartilage (dGEMRIC): molecular MRI of hip joint cartilage]

Factors such as instability and impingement lead to early cartilage damage and osteoarthritis of the hip joint. The surgical outcome of joint-preserving surgery about the hip joint depends on the preoperative quality of joint cartilage.For in vivo evaluation of cartilage quality, different biochemically sensitive magnetic resonance imaging (MRI) procedures have been tested, some of which have the potential of inducing a paradigm shift in the evaluation and treatment of cartilage damage and early osteoarthritis.Instead of reacting to late sequelae in a palliative way, physicians could assess cartilage damage early on, and the treatment intensity could be adequate and based on the disease stage. Furthermore, the efficiency of different therapeutic interventions could be evaluated and monitored.This article reviews the recent application of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and discusses its use for assessing cartilage quality in the hip joint. dGEMRIC is more sensitive to early cartilage changes in osteoarthritis than are radiographic measures and might be a helpful tool for assessing cartilage quality.

The association of preoperative anemia and perioperative allogeneic blood transfusion with the risk of surgical site infection

BACKGROUND: The purpose of the study was to investigate allogeneic blood transfusion (ABT) and preoperative anemia as risk factors for surgical site infection (SSI). STUDY DESIGN AND METHODS: A prospective, observational cohort of 5873 consecutive general surgical procedures at Basel University Hospital was analyzed to determine the relationship between perioperative ABT and preoperative anemia and the incidence of SSI. ABT was defined as transfusion of leukoreduced red blood cells during surgery and anemia as hemoglobin concentration of less than 120 g/L before surgery. Surgical wounds and resulting infections were assessed to Centers for Disease Control standards. RESULTS: The overall SSI rate was 4.8% (284 of 5873). In univariable logistic regression analyses, perioperative ABT (crude odds ratio [OR], 2.93; 95% confidence interval [CI], 2.1 to 4.0; p < 0.001) and preoperative anemia (crude OR, 1.32; 95% CI, 1.0 to 1.7; p = 0.037) were significantly associated with an increased odds of SSI. After adjusting for 13 characteristics of the patient and the procedure in multivariable analyses, associations were substantially reduced for ABT (OR, 1.25; 95% CI, 0.8 to 1.9; p = 0.310; OR, 1.07; 95% CI, 0.6 to 2.0; p = 0.817 for 1-2 blood units and >or=3 blood units, respectively) and anemia (OR, 0.91; 95% CI, 0.7 to 1.2; p = 0.530). Duration of surgery was the main confounding variable. CONCLUSION: Our findings point to important confounding factors and strengthen existing doubts on leukoreduced ABT during general surgery and preoperative anemia as risk factors for SSIs.

BMP-2 induces the expression of chondrocyte-specific genes in bovine synovium-derived progenitor cells cultured in three-dimensional alginate hydrogel

OBJECTIVE: According to recent reports, the synovial membrane may contain mesenchymal stem cells with the potential to differentiate into chondrocytes under appropriate conditions. In order to assess the usefulness of synovium-derived progenitor cells for the purposes of cartilage tissue engineering, we explored their requirements for the expression of chondrocyte-specific genes after expansion in vitro. DESIGN: Mesenchymal progenitor cells were isolated from the synovial membranes of bovine shoulder joints and expanded in two-dimensions on plastic surfaces. They were then seeded either as micromass cultures or as single cells within alginate gels, which were cultured in serum-free medium. Under these three-dimensional conditions, chondrogenesis is known to be supported and maintained. Cell cultures were exposed either to bone morphogenetic protein-2 (BMP-2) or to isoforms of transforming growth factor-beta (TGF-beta). The levels of mRNA for Sox9, collagen types I and II and aggrecan were determined by RT-PCR. RESULTS: When transferred to alginate gel cultures, the fibroblast-like synovial cells assumed a rounded form. BMP-2, but not isoforms of TGF-beta, stimulated, in a dose-dependent manner, the production of messenger RNAs (mRNAs) for Sox9, type II collagen and aggrecan. Under optimal conditions, the expression levels of cartilage-specific genes were comparable to those within cultured articular cartilage chondrocytes. However, in contrast to cultured articular cartilage chondrocytes, synovial cells exposed to BMP-2 continued to express the mRNA for alpha1(I) collagen. CONCLUSIONS: This study demonstrates that bovine synovium-derived mesenchymal progenitor cells can be induced to express chondrocyte-specific genes. However, the differentiation process is not complete under the chosen conditions. The stimulation conditions required for full transformation must now be delineated.

Beta1 integrin deficiency results in multiple abnormalities of the knee joint

The lack of beta1 integrins on chondrocytes leads to severe chondrodysplasia associated with high mortality rate around birth. To assess the impact of beta1 integrin-mediated cell-matrix interactions on the function of adult knee joints, we conditionally deleted the beta1 integrin gene in early limb mesenchyme using the Prx1-cre transgene. Mutant mice developed short limbed dwarfism and had joint defects due to beta1 integrin deficiency in articular regions. The articular cartilage (AC) was structurally disorganized, accompanied by accelerated terminal differentiation, altered shape, and disrupted actin cytoskeleton of the chondrocytes. Defects in chondrocyte proliferation, cytokinesis, and survival resulted in hypocellularity. However, no significant differences in cartilage erosion, in the expression of matrix-degrading proteases, or in the exposure of aggrecan and collagen II cleavage neoepitopes were observed between control and mutant AC. We found no evidence for disturbed activation of MAPKs (ERK1/2, p38, and JNK) in vivo. Furthermore, fibronectin fragment-stimulated ERK activation and MMP-13 expression were indistinguishable in control and mutant femoral head explants. The mutant synovium was hyperplastic and frequently underwent chondrogenic differentiation. beta1-null synoviocytes showed increased proliferation and phospho-focal adhesion kinase expression. Taken together, deletion of beta1 integrins in the limb bud results in multiple abnormalities of the knee joints; however, it does not accelerate AC destruction, perturb cartilage metabolism, or influence intracellular MAPK signaling pathways.

Selective iNOS-inhibition does not influence apoptosis in ruptured canine cranial cruciate ligaments

Abnormal patterns of cell death, including increased apoptosis, can influence homeostasis of ligaments and could be involved in the pathogenesis of cranial cruciate ligament (CCL) rupture. Increased nitric oxide (NO) production has been implicated as a stimulus to increased apoptosis in articular cartilage. This study investigated apoptotic cell death in ruptured canine CCL (CCL group, n = 15), in ruptured CCL of dogs treated with oral L-N6-(1-iminoethyl)-lysine (L-NIL), a selective NO-synthetase(NOS)-inhibitor, (L-NIL group, n = 15) and compared the results with normal canine CCL (control group, n = 10). Orally administered L-NIL at a dosage of 25mg/m2 of body surface area was effective in inhibiting NO production in the articular cartilage of dogs in the L-NIL group, but it did not significantly influence the increased quantity of apoptotic cells found in ruptured CCL specimens. The results of this study suggest that apoptosis of ligamentocytes in the canine CCL is not primarily influenced by increased NO production within the stifle joint.

Taxane-containing induction chemotherapy followed by definitive chemoradiotherapy. Outcome in patients with locally advanced head and neck cancer

BACKGROUND Induction chemotherapy followed by definitive chemoradiotherapy is an intensified treatment approach for locally advanced squamous cell carcinoma of the head and neck (HNSCC) that might be associated with high rates of toxicity. MATERIALS AND METHODS The data of 40 consecutive patients who underwent induction chemotherapy with docetaxel-containing regimens followed by intensity-modulated radiotherapy (IMRT) and concomitant systemic therapy for unresectable locally advanced HNSCC were retrospectively analyzed. Primary objectives were RT-related acute and late toxicity. Secondary objectives were response to induction chemotherapy, locoregional recurrence-free survival (LRRFS), overall survival (OS), and influencing factors for LRRFS and OS. RESULTS The median follow-up for surviving patients was 21 months (range, 2-53 months). Patients received a median of three cycles of induction chemotherapy followed by IMRT to 72 Gy. Three patients died during induction chemotherapy and one during chemoradiotherapy. Acute RT-related toxicity was of grade 3 and 4 in 72 and 3 % of patients, respectively, mainly dysphagia and dermatitis. Late RT-related toxicity was mainly xerostomia and bone/cartilage necrosis and was of grade 3 and 4 in 15 % of patients. One- and 2-year LRRFS and OS were 72 and 49 % and 77 and 71 %, respectively. CONCLUSION Induction chemotherapy followed by chemoradiotherapy using IMRT was associated with a high rate of severe acute and late RT-related toxicities in this selected patient cohort. Four patients were lost because of fatal complications. Induction chemotherapy did not compromise the delivery of full-dose RT; however, the use of three cycles of concomitant cisplatin was impaired.

Table-mounted ring retractor for consistent visualization in endoscopy-assisted anterior reconstruction of burst fractures of the thoracolumbar junction

The authors tested an autoclavable external ring retractor, fixed to the operation table, for the endoscopic reconstruction of anterior column injuries of the thoracolumbar junction. It served as a retractor for the diaphragm, and offered a stable support for the scope and other instruments, making an assistant superfluous. Moreover, it allowed bimanual manipulation. Of course, the two-dimensional image, provided by the scope, necessitated proper eye-hand coordination. Twenty-eight consecutive patients underwent either a monosegmental (n = 10) or a bisegmental (n = 18) anterior stabilization in the area Th11L1. Three portals were necessary, but an assistant was not needed. The overall (mean +/- SD) operating time was 196 +/- 56 min, the blood loss was 804 +/- 719 mL. Intraoperatively, one epidural bleeding and a single screw cut-out occurred. All complications were managed endoscopically. Postoperatively, evacuation of a haemothorax (n = 1) was necessary. In all patients, wounds and fractures healed uneventfully. The combination of the endoscopic technique and the retractor system was feasible, successful, safe, and time efficient. Moreover, it allowed for anterior instrumentation of thoracolumbar fractures by a single surgeon. It became the standard approach in the authors' department.

Experimentally induced cam impingement in the sheep hip

Sheep hips have a natural non-spherical femoral head similar to a cam-type deformity in human beings. By performing an intertrochanteric varus osteotomy, cam-type femoro-acetabular impingement (FAI) during flexion can be created. We tested the hypotheses that macroscopic lesions of the articular cartilage and an increased Mankin score (MS) can be reproduced by an experimentally induced cam-type FAI in this ovine in vivo model. Furthermore, we hypothesized that the MS increases with longer ambulatory periods. Sixteen sheep underwent unilateral intertrochanteric varus osteotomy of the hip with the non-operated hip as a control. Four sheep were sacrificed after 14, 22, 30, and 38-weeks postoperatively. We evaluated macroscopic chondrolabral alterations, and recorded the MS, based on histochemical staining, for each ambulatory period. A significantly higher prevalence of macroscopic chondrolabral lesions was found in the impingement zone of the operated hips. The MS was significantly higher in the acetabular/femoral cartilage of the operated hips. Furthermore, these scores increased as the length of the ambulatory period increased. Cam-type FAI can be induced in an ovine in vivo model. Localized chondrolabral degeneration of the hip, similar to that seen in humans (Tannast et al., Clin Orthop Relat Res 2008; 466: 273-280; Beck et al., J Bone Joint Surg Br 2005; 87: 1012-1018), can be reproduced. This experimental sheep model can be used to study cam-type FAI.

In vitro temperature evaluation during cement augmentation of proximal humerus plate screw tips

BACKGROUND The treatment of proximal humerus fractures in patients with poor bone quality remains a challenge in trauma surgery. Augmentation with polymethylmethacrylate (PMMA) cement is a possible method to strengthen the implant anchorage in osteoporotic bone and to avoid loss of reduction and reduce the cut-out risk. The polymerisation of PMMA during cement setting leads, however, to an exothermic reaction and the development of supraphysiological temperatures may harm the bone and cartilage. This study addresses the issue of heat development during augmentation of subchondrally placed proximal humerus plate screws with PMMA and the possible risk of bone and cartilage necrosis and apoptosis. METHODS Seven fresh frozen humeri from geriatric female donors were instrumented with the proximal humerus interlocking system (PHILOS) plate and placed in a 37°C water bath. Thereafter, four proximal perforated screws were augmented with 0.5 ml PMMA each. During augmentation, the temperatures in the subchondral bone and on the articular surface were recorded with K-type thermocouples. The measured temperatures were compared to threshold values for necrosis and apoptosis of bone and cartilage reported in the literature. RESULTS The heat development was highest around the augmented tips of the perforated screws and diminished with growing distance from the cement cloud. The highest temperature recorded in the subchondral bone reached 43.5°C and the longest exposure time above 42°C was 86s. The highest temperature measured on the articular surface amounted to 38.6°C and the longest exposure time above 38°C was 5 min and 32s. CONCLUSION The study shows that augmentation of the proximal screws of the PHILOS plate with PMMA leads to a locally limited development of supraphysiological temperatures in the cement cloud and closely around it. The critical threshold values for necrosis and apoptosis of cartilage and subchondral bone reported in the literature, however, are not reached. In order to avoid cement extravasation, special care should be taken in detecting perforations or intra-articular cracks in the humeral head.

Electrospinning Auricular Shaped Scaffolds for Tissue Engineering

Poly(ɛ)caprolactone scaffolds have been electrospun directly into an auricular shaped conductive mould. Bovine chondrocytes were harvested from articular cartilage and seeded onto 16 of the produced scaffolds, which received either an ethanol (group A) or a plasma treatment (group B) for sterilisation before seeding. The seeded scaffolds were cultured for 3 weeks in vitro and analysed with regard to total DNA and GAG content as well as the expression of AGG, COL1, COL2, MMP3 and MMP13. Rapid cell proliferation and GAG accumulation was observed until week 2. However, total DNA and GAG content decreased again in week 3. qPCR data shows a slight increase in the expression of anabolic genes and a slight decrease for the catabolic genes, with a significant difference between the groups A and B only for COL2 and MMP13.