Effect of articular cartilage proteoglycan depletion on high frequency ultrasound backscatter

AbstractObjective To study the effect of variations of articular cartilage proteoglycans (PG) on high-frequency ultrasound backscatter.Design The study was performed on patellar cartilages of immature and mature rats (N=36). The variation of PG content was induced by enzyme digestion. Control and treated cartilages were explored in vitro using a 55MHz scanning acoustic microscopy, then assessed by histology for the fibrillar collagen organization analysis. The variations of proteoglycan and collagen content were evaluated. Thickness measurements performed on both B-scan images and histologic sections were compared. Ultrasonic radio-frequency signals reflected by the cartilage surface and backscattered from its internal matrix were processed to estimate the integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB).Results Although hyaluronidase treatment of immature and mature cartilages removed approximately 50% of the proteoglycans, the echogenicity level of ultrasound images of degraded cartilages was similar to that of controls. IRC and AIB parameters did not significantly vary. Histologic sections of degraded cartilage displayed no change in collagen fiber organization. The thickness mean values measured by ultrasound in PG-depleted groups were significantly higher than in controls, whereas no significant difference in thickness was detected by histological measurement. The increase in cartilage thickness may potentially be explained by a decrease of speed of sound in PG-depleted cartilages that is more likely subsequent to an increase of water content.ConclusionCurrent results indicate that PG depletion has no significant effect on high frequency ultrasound backscattered from rat patellar cartilage. Ultrasound may provide information about variations of PG content via speed of sound measurement. Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved

Magnetic resonance imaging in osteoarthritis: which method best reflects synovial membrane inflammation? Correlations with clinical, macroscopic and microscopic features

SummaryObjectives: To study synovial membrane (SM) inflammation near the patella with different magnetic resonance imaging (MRI) approaches performed using a T1-injected sequence in knee osteoarthritis (OA), and to compare MRI results with macroscopic, microscopic and clinical findings.MethodsFifteen patients fulfilling American College of Rheumatology (ACR) criteria for knee OA and requiring joint lavage completed a functional index (Lequesne's functional index) and a pain visual analog scale (VAS). SM inflammation near the patella was assessed on axial fat saturation post-injected T1 MRI images using three different methods: (1) semi-quantitative score=MRI synovitis score; (2) synovial membrane volume (SMV) analysis; (3) SMV with low (SMVL) (<0.3%/s−1), intermediate (SMVI) (0.3%/s−1 to 1%/s−1) and high (SMVH) (≥1%/s−1) speed of enhancement. Chondral lesions and SM inflammation were macroscopically graded and SM biopsies performed for microscopic scoring.ResultsAll MRI approaches exhibited excellent intra- and inter-observer reproducibility. MRI synovitis score correlated well with macroscopic (r=0.61, P=0.003) and total microscopic scores (r=0.55, P=0.03). Correlations between SMV and macroscopic (r=0.60, P=0.02) and microscopic congestion (r=0.63, P=0.01) were good. SMVH was correlated only with microscopic congestion (r=0.79, P=0.01). Low SMV was associated with neither macroscopic nor microscopic scores. However, it did correlate well with pain-VAS score (r=0.61, P=0.03) and moderately with a functional index (r=0.46, P=0.10).ConclusionThe three MRI approaches used here provided highly reproducible information on SM inflammation near the patella in knee OA. Compared to SMV, MRI synovitis score seems sufficient to assess synovial inflammation but high SMV is an appropriate indicator of vascular congestion, and low SMV reflects pain in knee OA

The reliability of musculoskeletal ultrasound in the detection of cartilage abnormalities at the metacarpo-phalangeal joints

SummaryObjectiveTo assess the reliability of ultrasound (US) in detecting cartilage abnormalities at the metacarpo-phalangeal (MCP) joints in people with cartilage pathology.MethodsNine expert ultrasonographers initially achieved consensus on definitions and scanning protocols. They then examined the second to fifth MCP joints of the dominant hand of eight people with hand osteoarthritis (OA). US examinations were conducted in two rounds, with independent blinded evaluations of cartilage lesions. Global cartilage abnormalities were assessed by applying a dichotomous (presence/absence) score; in addition, the following lesions were evaluated using the same scoring system: loss of anechoic structure and/or thinning of the cartilage layer, and irregularities and/or loss of sharpness of at least one cartilage margin. Reliability was assessed using kappa (k) coefficients.ResultsThirty-two joints were examined. Intra-observer k values ranged from 0.52 to 1 for global cartilage abnormalities; k values ranged from 0.54 to 0.94 for loss of anechoic structure and/or thinning of cartilage layer and from 0.59 to 1 for irregularities and/or loss of sharpness of at least one cartilage margin. Values of k for inter-observer reliability were 0.80 for global cartilage abnormalities, 0.62 for loss of anechoic structure and/or thinning of cartilage layer, and 0.39 for irregularities and/or loss of sharpness of at least one cartilage margin.ConclusionUS is a reliable imaging modality for the detection of cartilage abnormalities in patients with cartilage pathology in the MCP joints. The analysis of specific cartilage measures showed more variable results that may be improved by modifying definitions and further standardization of US techniques

The reliability of musculoskeletal ultrasound in the detection of cartilage abnormalities at the metacarpo-phalangeal joints

Objective: To assess the reliability of ultrasound (US) in detecting cartilage abnormalities at the metacarpo-phalangeal (MCP) joints in people with cartilage pathology. Methods: Nine expert ultrasonographers initially achieved consensus on definitions and scanning protocols. They then examined the second to fifth MCP joints of the dominant hand of eight people with hand osteoarthritis (OA). US examinations were conducted in two rounds, with independent blinded evaluations of cartilage lesions. Global cartilage abnormalities were assessed by applying a dichotomous (presence/absence) score; in addition, the following lesions were evaluated using the same scoring system: loss of anechoic structure and/or thinning of the cartilage layer, and irregularities and/or loss of sharpness of at least one cartilage margin. Reliability was assessed using kappa (k) coefficients. Results: Thirty-two joints were examined. Intra-observer k values ranged from 0.52 to 1 for global cartilage abnormalities; k values ranged from 0.54 to 0.94 for loss of anechoic structure and/or thinning of cartilage layer and from 0.59 to 1 for irregularities and/or loss of sharpness of at least one cartilage margin. Values of k for inter-observer reliability were 0.80 for global cartilage abnormalities, 0.62 for loss of anechoic structure and/or thinning of cartilage layer, and 0.39 for irregularities and/or loss of sharpness of at least one cartilage margin. Conclusion: US is a reliable imaging modality for the detection of cartilage abnormalities in patients with cartilage pathology in the MCP joints. The analysis of specific cartilage measures showed more variable results that may be improved by modifying definitions and further standardization of US techniques. © 2012 Osteoarthritis Research Society International

Fungal colonization in Cystic Fibrosis (CF): Epidemiology and antifungal resistance in a French cohort of CF patients – Focused on Aspergillus fumigatus colonization

Introduction: Cystic fibrosis (CF) is the major genetic inherited disease in the European Caucasian population, with an average of 1 in 3000 living births in France. Prognostic depend essentially on the lung impairments. While considerable attention therefore has been paid over recent decades to prevent and treat bacterial respiratory infections, we observed emergence of fungi colonization in CF respiratory tract. In particular, Aspergillus fumigatus represents the most common causative agent colonizing the airways of CF patients; it can be responsible for Allergic Bronchopulmonary Aspergillosis (ABPA). Since oral corticosteroids and itraconazole represent the mainstay of ABPA treatment, long-term therapy may increase the risk of acquired resistance to azoles that is mainly associated with amino acid substitutions in the CYP51A gene of A. fumigatus. Objective: First, we managed to have exhaustive epidemiological data on species of filamentous fungi able to colonize the airway tract of 300 CF patients followed-up in our national prospective study ("MucoFong" study – PHRC1902). Second, CF patients being chronically exposed to azole (especially to itraconazole), our study aimed to evaluate the prevalence of azole resistance in isolates prospectively collected from CF patients followed-up in seven French hospitals involved in our national prospective study. Third, we focused on the most prevalent species: Aspergillus fumigatus, studying the azole resistance at molecular level. To our knowledge, it is the first multicenter study focused on azole resistance of A. fumigatus in CF. Methods: A total of 243 sputa were analyzed using the same protocol in each centre. The MICs of antifungal drugs were evaluated for each isolate using the E-test ® strips. Focusing on A. fumigatus, a total of 87 isolates was collected in 85 patients. These isolates were characterized at the molecular level by targeting ITS, ß-tubulin and MAT-A/α genes. The CYP51A gene as well as its promoter was sequenced; a 3D Cyp51A protein homology model was built. Results and discussion: 300 patients were enrolled in this study. At inclusion time, most of them were adults colonized with A. fumigatus (about 35% of the patients). Scedosporium was isolated in 5%, and Exophiala in about 2%. Regarding antifungal susceptibility, isolates of Scedosporium and Exophiala exhibited antifungal resistance comparable with published data. Regarding A. fumigatus, a majority of isolates (88.1%) were found sensitive to itraconazole (MIC≤ 2μg/ml), and 2 new mutations were identified and localized within 3-dimensional Cyp51A protein model. To obtain insight into azole resistance of A. fumigatus, the results are analyzed taking into account clinical data, itraconazole exposition, and the potential correlation between the identified CYP5IA mutations and azole resistance is discussed based on the Cyp51A protein homology model

Associations of lumbar scoliosis with presentation of suspected early axial spondyloarthritis

Objective: Scoliosis may impact the mechanical loading and cause secondary changes of the sacroiliac joints and lumbar spine. Our goal was to look how lumbar scoliosis modify the clinical and imaging-study in patients with recent-onset inflammatory back pain (IBP) suggesting axial spondyloarthritis (axSpA).Methods: Baseline weight-bearing lumbar-spine radiographs obtained in the DESIR cohort of patients aged 18-50 years and having IBP for at least 3 months but less than 3 years suggesting axSpA were studied. After training on scoliosis detection based on Cobb's angle>10 degrees plus Nash-Moe grade >= 1, readers blinded to patient data measured spine lumbar scoliosis, sacral horizontal angle, lumbosacral angle and lumbar lordosis on the radiograph of the lumbar and scored sacroiliitis on the radiograph of the pelvis. Baseline MRIs T1 and STIR of the lumbar spine and sacroiliac joints were evaluated for respectively degenerative changes and signs of axSpA.Results: Of the 360 patients (50.8% females) 88.7% had lumbar pain and 69.3% met ASAS criteria for axSpA. Mean Cobb's angle was 3.2 degrees +/- 5.0 degrees and 28 (7.7%) patients had lumbar scoliosis. No statistical differences were observed for radiographic sacroiliitis, MRI sacroiliitis, modified Stoke Ankylosing Spondylitis Spinal Score, Pfirmmann score, high-intensity zone, protrusion, extrusion, MODIC score between patients with and without scoliosis. In both groups, degenerative changes by MRI were rare and predominated at L4-L5 and L5-S1.Conclusion: In patients with early IBP suggesting axSpA, lumbar scoliosis was not associated with inflammatory or degenerative changes. (C) 2019 Elsevier Inc. All rights reserved.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Ultrasound in the evaluation of enthesitis: status and perspectives

Introduction: An increasing number of studies have applied ultrasound to the evaluation of entheses in spondyloarthritis patients. However, no clear agreement exists on the definition of enthesitis, on the number and choice of entheses to examine and on ultrasound technique, which may all affect the results of the examination. The objectives of this study were to first determine the level of homogeneity in the ultrasound definitions for the principal lesions of enthesitis in the published literature and second, to evaluate the metric properties of ultrasound for detecting enthesitis according to the OMERACT filter. Methods: Search was performed in PUBMED and EMBASE. Both grey-scale and Doppler definitions of enthesitis, including describing features of enthesitis, were collected and metrological qualities of studies were assessed. Results: After selection, 48 articles were analyzed. The definition of ultrasound enthesitis and elementary features varied among authors. Grey-scale enthesitis was characterized by increasing thickness (94% of studies), hypoechogenicity (83%), enthesophytes (69%), erosions (67%), calcifications (52%), associated bursitis (46%) and cortical irregularities (29%). Only 46% of studies reported the use of Doppler. High discrepancies were observed on frequency, type of probe and Doppler mode used. Face and content validity were the most frequently evaluated criteria (43%) followed by reliability (29%) and responsiveness (19%). Conclusions: Ultrasound has evidence to support face, content validity and reliability for the evaluation of enthesitis, though there is a lack of well-reported methodology in most of the studies. Consensus on elementary lesions and standardization of exam is needed to determine the ultrasound definition of enthesitis in grey-scale and in Doppler for future applications.15 page(s

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures