Traumatic patellar dislocation in childhood : late effects on knee function and cartilage quality

Background and aim: Acute patellar dislocation affects approximately 1:1000 healthy children 9- 15 years of age, and up to 50% are at risk for recurrent dislocations. In adults the condition is associated with long-term complications, such as osteoarthritis and impairment of knee function. However, literature describing the outcome in a pediatric population is sparse. The aim of this thesis was to evaluate the long-term effects on knee function and cartilage quality after traumatic patellar dislocation in childhood, and also to evaluate the reliability of two clinical tests of medio-lateral knee position, in healthy children. Patients and methods: In Study I, 246 healthy children were included to evaluate the Q-angle and the Single-limb mini squat test, reflecting static and dynamic medio-lateral knee position, respectively. In Study II, III and IV patients with a history of acute, unilateral, first-time traumatic patellar dislocation, 9-15 years of age at index injury, and with a follow-up time of ≥5 years were included. Recurrence rate and patient reported outcome were assessed. In Study II, n=52, the objective- and subjective knee function were evaluated in relation to type of obtained treatment. In Study III and IV the quality of the patellar cartilage was evaluated with quantitative MRI metrics, T2 mapping and delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC). In Study III 16 non-operatively treated patients with recurrent patellar dislocation, and in Study IV 17 patients surgically treated in childhood due to unilateral recurrent patellar dislocation, were evaluated. Results: In Study I the reliability for the Single-limb mini squat test was determined moderate, the Q-angle measurement was found to have fair to moderate reliability. The Q-angle varied with age and sex; however, this finding may not be clinically relevant. Study II, III and IV reveal that the patients were affected KOOS quality of life and sports and recreation, with lower scores than normal for the age. 67% reported recurrence among the non-operatively treated patients. Despite regained stability in patients operated on due to recurrences, the subjective knee function was not restored. In both the non-operatively treated patients with recurrent patellar dislocations (Study III), and the surgically stabilized patients (Study IV), very early cartilage changes were detected in the patellar cartilage of the affected knee with dGEMRIC and T2 mapping. The shortening of T1(Gd) indicate loss of glycosaminoglycans. The localization of the findings were similar in Study III and IV, although, at different tissue depths; with changes in the superficial half of the cartilage in patients with recurrent dislocations (study III), and changes in the deep half in the operated patients (study IV). In Study III shorter T2 values were detected in superficial half of the cartilage in the peripheral parts of affected patella, whereas longer T2 was observed most medially in the deep cartilage of the operated group (Study IV). Conclusion: The Single-limb mini squat test can be used to evaluate the medio-lateral knee position in a pediatric population, whereas the Q-angle only showed fair reliability. Acute traumatic patellar dislocation in childhood has a negative long-term impact on quality of life and ability to participate in physical activities. Traditional surgical methods reduced the recurrence rate, but the knee function was not restored. Recurrent patellar dislocation, and patellar stabilizing surgery, seem to have a negative effect on cartilage quality; most likely through different biological mechanisms and at different depths of the cartilage. The results from quantitative MRI of the patellar cartilage indicate changes in both GAG content and collagen structure. These new findings show that dGEMRIC, in combination with T2 mapping, are feasible methods to detect early degenerative changes in vivo in this condition

Wave functions associated with time-dependent, complex-scaled Hamiltonians evaluated on a complex time grid

We solve the time-dependent Schrödinger equation with themethod of uniform complex scaling and investigate the possibility to evaluate the solution on a complex time grid. With this approach it is possible to calculate properties that relate directly to the continuum part of the complex scaledwave function, such as the photoelectron spectrum after photoabsorption

Long-Term Follow-Up of Nonoperatively and Operatively Treated Acute Primary Patellar Dislocation in Skeletally Immature Patients

Purpose. The present study reports a long-term follow-up of acute primary patellar dislocation in patients with open physes. The purpose of the study was to evaluate knee function and recurrence rates after surgical and nonsurgical treatment of patellar dislocation. Methods. A total of 51 patients, including 29 girls and 22 boys, who were 9–14 years of age at the time of injury, were retrospectively evaluated. The minimum follow-up time was 5 years. Thigh muscle torque, range of motion, the squat test, the knee injury and osteoarthritis outcome score (KOOS), the Kujala score, and the recurrence rate were registered. Radiological predisposing factors at the time of injury were determined. Results. Quality of life and sports/recreation were the most affected subscales, according to KOOS, and a reduced Kujala score was also observed in all treatment groups. The surgically treated patients had a significantly lower recurrence rate. Those patients also exhibited reduced muscle performance, with a hamstring to quadriceps ratio (H/Q) of 1.03. The recurrence rate was not correlated with knee function. Conclusions. Patellar dislocation in children influences subjective knee function in the long term. Surgery appears to reduce the recurrence rate, but subjective knee function was not restored

Expression of fibromodulin in carotid atherosclerotic plaques is associated with diabetes and cerebrovascular events.

The small leucine-rich proteoglycans fibromodulin and lumican are functionally related extracellular matrix proteins involved in the regulation of collagen fiber formation. Fibromodulin-deficient apolipoprotein E-null mice have decreased vascular retention of lipids and reduced development of atherosclerosis suggesting that fibromodulin may influence the disease process. The aim of the present study was to investigate if fibromodulin and lumican are expressed in human carotid plaques and to determine if their expression is associated with the occurrence of preoperative symptoms and with risk for postoperative cardiovascular events

Why Achieving the Paris Agreement Requires Reduced Overall Consumption and Production

Technological solutions to the challenge of dangerous climate change are urgent and necessary but to be effective they need to be accompanied by reductions in the total level of consumption and production of goods and services. This is for three reasons. First, private consumption and its associated production are among the key drivers of greenhouse-gas (GHG) emissions, especially among highly emitting industrialized economies. There is no evidence that decoupling of the economy from GHG emissions is possible at the scale and speed needed. Second, investments in more sustainable infrastructure, including renewable energy, needed in coming decades will require extensive amounts of energy, largely from fossil sources, which will use up a significant share of the two-degree carbon budget. Third, improving the standard of living of the world’s poor will consume a major portion of the available carbon allowance. The scholarly community has a responsibility to put the issue of consumption and the associated production on the research and policy agenda

Increased aldehyde-modification of collagen type IV in symptomatic plaques - A possible cause of endothelial dysfunction.

Subendothelial LDL-adhesion and its subsequent oxidation are considered as key events in the development of atherosclerotic lesions. During oxidation of LDL, reactive aldehydes such as malondialdehyde (MDA) are formed, which modify apolipoprotein B100. However, the possibility that these reactive aldehydes could leak out of the LDL-particle and modify surrounding extracellular matrix proteins has been largely unexplored. We have investigated if aldehyde-modification of collagen type IV, one of the major basement membrane components, in plaques is associated with cardiovascular events

Plasma fibronectin deficiency impedes atherosclerosis progression and fibrous cap formation

Atherosclerotic lesions are asymmetric focal thickenings of the intima of arteries that consist of lipids, various cell types and extracellular matrix (ECM). These lesions lead to vascular occlusion representing the most common cause of death in the Western world. The main cause of vascular occlusion is rupture of atheromatous lesions followed by thrombus formation. Fibronectin (FN) is one of the earliest ECM proteins deposited at atherosclerosis-prone sites and was suggested to promote atherosclerotic lesion formation. Here, we report that atherosclerosis-prone apolipoprotein E-null mice lacking hepatocyte-derived plasma FN (pFN) fed with a pro-atherogenic diet display dramatically reduced FN depositions at atherosclerosis-prone areas, which results in significantly smaller and fewer atherosclerotic plaques. However, the atherosclerotic lesions from pFN-deficient mice lacked vascular smooth muscle cells and failed to develop a fibrous cap. Thus, our results demonstrate that while FN worsens the course of atherosclerosis by increasing the atherogenic plaque area, it promotes the formation of the protective fibrous cap, which in humans prevents plaques rupture and vascular occlusion

Proliferation and differentiation potential of chondrocytes from osteoarthritic patients

Autologous chondrocyte transplantation (ACT) has been shown, in long-term follow-up studies, to be a promising treatment for the repair of isolated cartilage lesions. The method is based on an implantation of in vitro expanded chondrocytes originating from a small cartilage biopsy harvested from a non-weight-bearing area within the joint. In patients with osteoarthritis (OA), there is a need for the resurfacing of large areas, which could potentially be made by using a scaffold in combination with culture-expanded cells. As a first step towards a cell-based therapy for OA, we therefore investigated the expansion and redifferentiation potential in vitro of chondrocytes isolated from patients undergoing total knee replacement. The results demonstrate that OA chondrocytes have a good proliferation potential and are able to redifferentiate in a three-dimensional pellet model. During the redifferentiation, the OA cells expressed increasing amounts of DNA and proteoglycans, and at day 14 the cells from all donors contained type II collagen-rich matrix. The accumulation of proteoglycans was in comparable amounts to those from ACT donors, whereas total collagen was significantly lower in all of the redifferentiated OA chondrocytes. When the OA chondrocytes were loaded into a scaffold based on hyaluronic acid, they bound to the scaffold and produced cartilage-specific matrix proteins. Thus, autologous chondrocytes are a potential source for the biological treatment of OA patients but the limited collagen synthesis of the OA chondrocytes needs to be further explained

Soluble CD40 levels in plasma are associated with cardiovascular disease and in carotid plaques with a vulnerable phenotype

Background and Purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability. Methods Soluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro-and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and sCD40L were measured in atherosclerotic plaque homogenates from 199 subjects of the Carotid Plaque Imaging Project (CPIP) cohort. Results Both plasma sCD40 and sCD40L levels were elevated in individuals with prevalent stroke, while sCD40 levels also were higher in individuals with a prior acute myocardial infarction. Plasma levels of sCD40 correlated with carotid intima-media thickness and total carotid plaque area and were associated with risk of cardiovascular events over a 3-year follow-up period. Intra-plaque levels of sCD40 and sCD40L were associated with plaque components characteristic for plaque vulnerability and extracellular matrix remodelling. Conclusions Higher plasma sCD40 and sCD40L levels are associated with prevalent CVD. Plasma sCD40 levels also correlate with the severity of carotid atherosclerosis and predict future cardiovascular events, while intra-plaque levels correlate with a vulnerable plaque phenotype. Our findings thus demonstrate that elevated levels of sCD40 and sCD40L are markers of CVD.</p