The role of imaging in early hip OA

SummaryHip osteoarthritis (OA) is characterized by cartilage degradation, subchondral bone sclerosis and osteophyte formation. Nowadays, OA is thought to develop via different etiologies that all lead to a similar form of end stage joint degradation. One of these subtypes is related to an abnormal shaped hip joint, like acetabular dysplasia and a cam deformity. These bony abnormalities are highly predictive for development of hip OA, but they are likely to already be present from childhood. This suggests that these deformations induce OA changes in the hip, well before extensive hip degradation becomes present three to four decades later. Accurate detection and successful characterization of these early OA events might lead to better treatment options for hip OA besides nowadays available invasive joint replacement surgery. However, current diagnostic imaging techniques like radiographs or plain magnetic resonance imaging (MRI), are not sensitive enough to detect these subtle early OA changes. Nor are they able to disentangle intertwined and overlapping cascades from different OA subtypes, and neither can they predict OA progression. New and more sensitive imaging techniques might enable us to detect first OA changes on a cellular level, providing us with new opportunities for early intervention. In this respect, shape analysis using radiography, MRI, computed tomography (CT), single photon emission computed tomography (SPECT)/CT, and positron emission tomography (PET) might prove promising techniques and be more suited to detect early pathological changes in the hip joint. A broad application of these techniques might give us more understanding what can be considered physiological adaptation of the hip, or when early OA really starts. With a more clear definition of early OA, more homogenous patient populations can be selected and help with the development of new disease modifying OA interventions

Osteoarthritis: pathogenesis and therapeutic interventions for a whole joint disease

__Abstract__ Osteoarthritis (OA) is an invalidating disease characterized by progressive cartilage degradation. OA is the most prevalent arthritic disease and leading cause of disability that effects approximately 34% of the population in the United states over age 65. Also in the Netherlands, approximately 30% of persons aged 65 and older are affected in either the hip or knee joint by this severely disabling disease. Due to the obvious cartilage pathology, research has much focused on articular cartilage and chondrocyte pathobiology. Over the years more knowledge has been gained on complex biochemical and biomechanical influences of chondrocyte behavior. During the past decade, however, pathologic cellular and structural changes in subchondral and trabecular bone, ligaments, synovium, supporting musculature, fibrocartilagenous structures such as the meniscus, and intra-articular fat tissue support the idea that osteoarthritis is not just a cartilage problem. In the current dogma, OA is explained as ‘a whole joint disease’ that involves a degenerative continuum between multiple joint tissues and cell types

Citation analysis of orthopaedic literature; 18 major orthopaedic journals compared for Impact Factor and SCImago

<p>Abstract</p> <p>Background</p> <p>One of the disadvantages of the Impact Factor (IF) is self-citation. The SCImago Journal Rank (SJR) indicator excludes self-citations and considers the quality, rather than absolute numbers, of citations of a journal by other journals. The present study re-evaluated the influence of self-citation on the 2007 IF for 18 major orthopaedic journals and investigated the difference in ranking between IF and SJR.</p> <p>Methods</p> <p>The journals were analysed for self-citation both overall and divided into a general group (n = 8) and a specialized group (n = 10). Self-cited and self-citing rates, as well as citation densities and IFs corrected for self-citation (cIF), were calculated. The rankings of the 18 journals by IF and by SJR were compared and the absolute difference between these rankings (ΔR) was determined.</p> <p>Results</p> <p>Specialized journals had higher self-citing rates (p = 0.01, Δmedian = 9.50, 95%CI -19.42 to 0.42), higher self-cited rates (p = 0.0004, Δmedian = -10.50, 95%CI -15.28 to -5.72) and greater differences between IF and cIF (p = 0.003, Δmedian = 3.50, 95%CI -6.1 to 13.1). There was no significant correlation between self-citing rate and IF for both groups (general: r = 0.46, p = 0.27; specialized: r = 0.21, p = 0.56). When the difference in ranking between IF and SJR was compared between both groups, sub-specialist journals were ranked lower compared to their general counterparts (ΔR: p = 0.006, Δmedian = 2.0, 95%CI -0.39 to 4.39).</p> <p>Conclusions</p> <p>Citation analysis shows that specialized orthopaedic journals have specific self-citation tendencies. The correlation between self-cited rate and IF in our sample was large but, due to small sample size, not significant. The SJR excludes self-citations in its calculation and therefore enhances the underestimation in ranking of specialized journals.</p

Принцип коеволюції в контексті ноосферної концепції В.Вернадського

Досліджується принцип коеволюції людини та природи в контексті ноосферного вчення В.Вернадського. Аналізуються особливості світогляду суспільства ноосферної цивілізації.Исследуется принцип коэволюции человека и природы в контексте ноосферного учения В.Вернадского. Анализуются особенности мировоззрения общества ноосферной цивилизации.The principle of coevolution of person and nature is investigated in the context of noospherian doctrine of V.Vernadsky. The particularities of world view оf society of noospherian civilization are analyzed

Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression

Maturation of high-affinity B lymphocytes is precisely controlled during the germinal center reaction. This is dependent on CD4(+)CXCR5(+) follicular helper T cells (TFH) and inhibited by CD4(+)CXCR5(+)Foxp3(+) follicular regulatory T cells (TFR). Because NFAT2 was found to be highly expressed and activated in follicular T cells, we addressed its function herein. Unexpectedly, ablation of NFAT2 in T cells caused an augmented GC reaction upon immunization. Consistently, however, TFR cells were clearly reduced in the follicular T cell population due to impaired homing to B cell follicles. This was TFR-intrinsic because only in these cells NFAT2 was essential to up-regulate CXCR5. The physiological relevance for humoral (auto-)immunity was corroborated by exacerbated lupuslike disease in the presence of NFAT2-deficient TFR cells

Properties of commonly used calcium phosphate cements in trauma and orthopaedic surgery

Introduction Half of the population sustains at least one fracture during their lifetime, and the majority of these fractures heal successfully. Successful fracture healing requires the following five elements; (i) osteogenic cells (e.g., osteoblasts), (ii) osteoinductive stimuli (e.g., bone morphogenetic proteins); (iii) an osteoconductive matrix; (iv) adequate blood and nutrient supply, and (v) sufficient mechanical support. One or more elements can be compromised due to the existence of a bone defect. Bone defects are treated with bone grafts in order to avoid insufficient fracture healing. Insufficient fracture healing is encountered in 5–10% of the fractures, resulting in delayed union, malunion, or non-union

FK506 protects against articular cartilage collagenous extra-cellular matrix degradation

Objective: Osteoarthritis (OA) is a non-rheumatologic joint disease characterized by progressive degeneration of the cartilage extra-cellular matrix (ECM), enhanced subchondral bone remodeling, activation of synovial macrophages and osteophyte growth. Inhibition of calcineurin (Cn) activity through tacrolimus (FK506) in invitro monolayer chondrocytes exerts positive effects on ECM marker expression. This study therefore investigated the effects of FK506 on anabolic and catabolic markers of osteoarthritic chondrocytes in 2D and 3D invitro cultures, and its therapeutic effects in an invivo rat model of OA. Methods: Effects of high and low doses of FK506 on anabolic (QPCR/histochemistry) and catabolic (QPCR) markers were evaluated invitro on isolated (2D) and ECM-embedded chondrocytes (explants, 3D pellets). Severe cartilage damage was induced unilaterally in rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with FK506 orally and compared to twenty untreated controls. Subchondral cortical and trabecular bone changes (longitudinal microCT) and macrophage activation (SPECT/CT) were measured. Articular cartilage was analyzed exvivo using contrast enhanced microCT and histology. Results: FK506 treatment of osteoarthritic chondrocytes invitro induced anabolic (mainly collagens) and reduced catabolic ECM marker expression. In line with this, FK506 treatment clearly protected ECM integrity invivo by markedly decreasing subchondral sclerosis, less development of subchondral pores, depletion of synovial macrophage activation and lower osteophyte growth. Conclusion: FK506 protected cartilage matrix integrity invitro and invivo. Additionally, FK506 treatment invivo reduced OA-like responses in different articular joint tissues and thereby makes Cn an interesting target for therapeutic intervention of OA

The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6

Follicular T helper (Tfh) cells are key regulators of the germinal center reaction and long-term humoral immunity. Tfh cell differentiation requires the sustained expression of the transcriptional repressor Bcl6; however, its regulation in CD4(+) T cells is incompletely understood. Here, we report that the transcriptional coactivator Bob1, encoded by the Pou2af1 gene, promotes Bcl6 expression and Tfh cell development. We found that Bob1 together with the octamer transcription factors Oct1/Oct2 can directly bind to and transactivate the Bcl6 and Btla promoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 and BTLA, thereby controlling the pool size and composition of the Tfh compartment in a T cell-intrinsic manner. Our data indicate that T cell-expressed Bob1 is directly involved in Tfh cell differentiation and required for mounting normal T cell-dependent B-cell responses

Congenital Forearm Pseudarthrosis, a Systematic Review for a Treatment Algorithm on a Rare Condition

Background: A congenital forearm pseudarthrosis is a rare condition and is strongly associated with neurofibromatosis type 1. Several surgical techniques are described in the literature, but the most optimal treatment strategy remains unclear. This systematic review aims to develop a treatment algorithm that may aid i

Periarticular Bone Changes in Osteoarthritis

Osteoarthritis (OA) can be considered an organ failure with pathological aspects in cartilage, bone, ligaments, and synovium. Altogether, these tissue changes can result in pain and immobilization—a failure of the joint. It is well regarded that OA is a complex multifactorial disease with many risk factors and different etiological pathways that all lead to an apparently similar end stage. Bony changes are clearly observed in advanced OA. However, little understanding exists on the role of these changes, whether they are a consequence of cartilage damage or precede this damage and maybe play an important role in the etiological process. Even more important is the issue of pain. Radiological scores of OA do not match well with pain and mobility scores, which questions the value of these scoring systems. It seems that we do not assess the most relevant parameters. Evaluation of conventional and new radiographic parameters is still an extensive part of the OA research field. We may have overlooked certain (subtle) parameters that can be extracted from x-rays, but other imaging modalities such as MRI, CT, or SPECT might better represent OA in a clinically relevant manner