No description available.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Bakgrund: Excentrisk träning (ECC) har varit det dominerande träningssättet vid patellar tendinopati (PT) under de senaste 15 åren. Det skulle vara av värde för kliniker att veta vilken effekt ECC har på kort sikt efter en träningsperiod. Syfte: Systematiskt granska enskilda artiklar och bedöma tillförlitligheten i det sammanvägda resultatet gällande effekten på funktion och smärta samt förmåga att delta i sport eller fysiska aktiviteter som excentrisk träning har efter en träningsperiod på 12 veckor hos idrottande personer med PT. Design: Systematisk granskning av randomiserade kontrollerade studier. Metod: Sökningar utfördes i PubMed, CINAHL, PEDro och Cochrane library. Sju studier inkluderades och granskades med PEDro Scale. GRADEstud användes för att bedöma tillförlitligheten i resultatet. Resultat: Inkluderade studiers kvalitet varierade mellan acceptabel och hög kvalitet, enligt PEDro Scale. Det var inga skillnader mellan ECC och kontrollbehandlingar. Vid sammanvägningen av studiernas respektive resultat ansågs tillförlitligheten enligt GRADEstud vara måttligt hög (+++) p.g.a. hög samstämmighet, men bristande precision. Slutsats: ECC är inte mer effektivt än andra undersökta kontrollbehandlingar, därav kan denna studie inte säkerställa att förbättringar som sker efter 12 veckor beror på ECC. / Background: Eccentric exercise (ECC) has been the dominant treatment option for patellar tendinopathy (PT) in the last 15 years. It would be of value to clinicians to know about the short-term effect ECC has after a training period. Objective: Systematically review individual articles and assess the certainty in the weighted result regarding the effect on function, pain, and the ability to participate in sport and physical activities that eccentric training has after a 12week period of training on athletes with PT. Design: Systematic review of randomized controlled trials.                                           Method: Searches were conducted in PubMed, CINAHL, PEDro and Cochrane Library. Seven studies were included and reviewed with the PEDro Scale. GRADE-stud was used to assess the certainty in the result.  Results: Included studies quality varied between acceptable and high quality, according to the PEDro Scale. There were no differences between ECC and control treatments. When weighing the respective results of the studies, the certainty was considered moderately high (+++) according to GRADEstud, due to high coherence in all included studies, but a lack of precision. Conclusion: ECC is not more effective than other control therapies studied. Therefore, this study cannot ensure that improvements that occur after 12 weeks are due to ECC.

Diss. (sammanfattning) Göteborg : Univ. , 2006. / Härtill 5 uppsatser.

Patellar tendinopathy (PT) is a knee injury resulting in pain localized to the patellar tendon. One main factor that causes PT is repetitive overloading of the tendon. Because of this mechanism, PT is commonly seen in "jumping sports" like basketball. This injury can severely impact a player's performance, and in order for a timely return to preinjury activity levels early diagnosis and treatment is important. The standard for the diagnosis of PT is a clinical examination, including a patient history and a physical assessment. Because PT has similar symptoms to injuries of other knee structures like the bursae, fat pad, and patellofemoral joint, imaging is regularly performed to aid in determining the correct diagnosis. One common imaging modality for the patellar tendon is gray-scale ultrasonography (GS-US). However, the accurate detection of PT in GS-US images is grader dependent and requires a high level of expertise. Machine learning (ML) models, which can accurately and objectively perform image classification tasks, could be used as a reliable automated tool to aid clinicians in assessing PT in GS-US images. ML models, like support vector machines (SVMs) and convolutional neural networks (CNNs), use features learned from labelled images, to predict the class of an unlabelled image. SVMs work by creating an optimal hyperplane between classes of labelled data points, and then classifies an unlabelled datapoint depending on which side of the hyperplane it falls. CNNs work by learning the set of features and recognizing what pattern of features describes each class. The objective of this study was to develop a SVM model and a CNN model to classify GS-US images of the patellar tendon as either normal or diseased (PT present), with an accuracy around 83%, the accuracy that experienced clinicians achieved when diagnosing PT in GS-US images that were already clinically diagnosed as either diseased or normal. We will also compare different test designs for each model to determine which achieved the highest accuracy. GS-US images of the patellar tendon were obtained from male and female Virginia Tech collegiate basketball athletes. Each image was labelled by an experienced clinician as either diseased or normal. These images were split into training and testing sets. The SVM and the CNN models were created using Python. For the SVM model, features were extracted from the training set using speeded up robust features (SURF). These features were then used to train the SVM model by calculating the optimal weights for the hyperplane. For the CNN model, the features were learned by layers within the CNN as were the optimal weights for classification. Both of these models were then used to predict the class of the images within the testing set, and the accuracy, sensitivity and precision of the models were calculated. For each model we looked at different test designs. The balanced designs had the same amount of diseased and normal images. The designs with Long images had only images taken in the longitudinal orientation, unlike Long+Trans, which had both longitudinal and transverse images. The designs with Full images contained the patellar tendon and surrounding tissue, whereas the ROI images removed the surrounding tissue. The best designs for the SVM model were the Unbalanced Long designs for both the Full and ROI images. Both designs had an accuracy of 77.5%. The best design for the CNN model was the Balanced Long+Trans Full design, with an accuracy of 80.3%. Both of the models had more difficulty classifying normal images than diseased images. This may be because the diseased images had a well defined feature pattern, while the normal images did not. Overall, the CNN features and classifier achieved a higher accuracy than the SURF features and SVM classifier. The CNN model is only slightly below 83%, the accuracy of an experienced clinician. These are promising results, and as the data set size increases and the models are fine tuned, the accuracy of the model will only continue to increase. / Master of Science / Patellar tendinopathy (PT) is a common knee injury. This injury is frequently seen in sports like basketball, where athletes are regularly jumping and landing, and ultimately applying a lot of force onto the patellar tendon. This injury can severely impact a player's performance, and in order for a timely return to preinjury activity levels early diagnosis and treatment is important. Currently, diagnosis of PT involves a patient history and a physical assessment, and is commonly supplemented by ultrasound imaging. However, clinicians need to have a high level of expertise in order to accurately assess these images for PT. In order to aid in this assessment, a tool like Machine learning (ML) models could be used. ML is becoming more and more prevalent in our every day lives. These models are everywhere, from the facial recognition tool on your phone to the list of recommended items on your Amazon account. ML models can use features learned from labelled images, to predict the class of an unlabeled image. The objective of this study was to develop ML models to classify ultrasound images of the patellar tendon as either normal or diseased (PT present).

Achilles tendinopathy is a prevalent, highly debilitating condition. It is believed to result from repetitive overuse, which creates micro-damage tendon, and initiates a catabolic cell response. The aetiology of tendinopathy remains poorly understood, therefore appropriate treatment remains unclear. Current data support the use of shock wave therapy and eccentric exercise as some of the more effective treatment options for tendinopathy. Studies have shown that these treatments generate perturbations within tendon at a frequency of approximately 8-12Hz. Consequently, it is hypothesised that 10Hz loading initiates increased anabolic tenocyte behaviour promoting tendon repair. The primary aim of this thesis is to investigate the effects of 10Hz perturbations on tenocyte metabolism, comparing tenocyte gene expression in response to a 10Hz and 1Hz loading profile. A variety of in vitro models for mechanically stimulating cells were explored, comparing tissue explants with isolated cells on a 2D or within a 3D collagen gel. The mechanical environment of each model was investigated, in addition to cell viability and gene stabilisation following strain, as needed for future cell studies. 3D collagen gels arose as the most suitable model. Human tenocytes from healthy semitendinosus and tendinopathic Achilles tendons were seeded into 3D collagen gels and subjected to cyclic strain at 10Hz and 1Hz to establish cell response. Tenocyte gene expression was characterised using qRT-PCR. Healthy tenocytes showed increased expression of all analysed genes in response to loading. Furthermore, the increase was significantly larger in the 10Hz loading group. Tendinopathic tenocytes showed a more varied response, possibly indicative of an early healing response. Nevertheless, the response to 10Hz loading was consistently greater than seen with 1Hz loading. Analysis of the signalling pathways involved suggested that the IL1 signalling pathway may be involved in the strain response reported. This study has demonstrated for the first time that loading at a frequency of 10Hz may enhance metabolic response in healthy tenocytes.

Chronic painful tendinopathy is a common cause for elite- and recreational athletes to stop or decrease the level of their sports activity. Recent research on innervation patterns, histopathology and possible pain mechanisms in tendons has led to an increased knowledge about the chronic painful tendon. Ultrasound (US) and colourDoppler (CD) examination showing localized high blood flow, inside and outside regions with structural tendon abnormalities, has been shown to be of importance for tendon pain. Immuno-histochemical analyses of biopsies have shown sensory and sympathetic nerves in close relation to the high blood flow outside the tendon. These findings have led to new ideas about development of new treatment methods for chronic painful tendinopathy. In study I, we evaluated the already in use, US-guided sclerosing polidocanol injection treatment of midportion Achilles tendinopathy, using two different concentrations of the substance. This study aimed to find out if there was a faster return to pain-free activity by using the concentration 10 mg/ml compared to the formerly used 5 mg/ml. There were no significant differences in the clinical results between the groups. In study II - Technical note, we aimed to develop a new one-stage surgical treatment method for patellar tendinopathy. This method was based on research concerning the innervation patterns and US and CD findings in patellar tendinopathy/ “jumper’s knee”. Technically we added ultrasound guidance to knee arthroscopy to identify and visualize the region of interest during a surgical shaving procedure. In study III, we tested the newly invented US and CD-guided arthroscopic shaving technique in a pilot study. The short-term clinical results were promising and the majority of the patients returned to pain-free activity after a short rehabilitation period. In study IV, we compared the US and CD-guided artrhroscopic shaving method with the already in use sclerosing polidocanol injection treatment in a randomized study. At short-term follow-up, the patients treated with US and CD-guided arthroscopic shaving had significantly less pain during rest and activity, were significantly more satisfied with the treatment, and had a faster return to sports, compared to the patients in the sclerosing injection group. There were no complications. In study V, at longer-term followup (endpoint 46 months) there was a significant decrease in pain during activity in both groups. There were no remaining significant differences in the pain levels during activity between the groups. The tendon structure had improved significantly in both groups. There was a significant decrease in the antero-posterior thickness of the proximal patellar tendon in patients treated with US and CD-guided arthroscopic shaving, but not in the sclerosing injection group. The CD flow had diminished significantly in both groups, and there was a correlation between low CD flow and high patient satisfaction in both groups, The CD flow decreased faster in the surgical group than in the injection group. In conclusion, this newly invented US and CD-guided arthroscopic shaving treatment, focusing on treatment outside the tendon, has shown good clinical results with pain relief and a fast return to sports activity, in patients with patellar tendinopathy.

Diss. (sammanfattning) Umeå : Umeå universitet, 2007. / Härtill 7 uppsatser.

<p>Introduction: Diabetes mellitus is a major risk factor for tendon pain, injury, and pathology. Surprisingly, tendon problems persist in diabetic patients with superior blood glucose control (HbA1c<6.5), suggesting that alternative mechanisms contribute to this problem. Advanced glycation end products (AGEs) have been implicated in several diabetes-related complications, but their role in diabetic tendon pathology has not fully been explored. To expand our understanding of AGE-mediated tendon pathology, the following five studies were completed.</p><p>Study 1: Streptozotocin-induced diabetes alters transcription of multiple genes necessary for extracellular matrix remodeling in rat patellar tendon. RNA was isolated from the patellar tendon of non-diabetic (control, n=9), 1-week diabetic (acute, n=8), 10-weeks diabetic (chronic, n=7), and insulin treated 10-weeks diabetic (insulin, n=8) rats. Determination of mRNA transcripts was completed using droplet digital PCR (ddPCR). Our findings indicated that STZ-induced diabetes results in rapid and large changes in the expression of several genes that are key to extracellular matrix (ECM) remodeling, maintenance, and maturation.</p><p>Study 2: Advanced glycation end products suppress mitochondrial function and proliferative capacity of Achilles tendon-derived fibroblasts. Using an <i>in vitro</i> cell culture system, rat Achilles tendon fibroblasts were treated with glycolaldehyde-derived AGEs (0, 50, 100, and 200μg/ml) for 48 hours in normal glucose (5.5mM) and high glucose (25mM) conditions. Our findings demonstrate that tendon fibroblasts treated with AGEs display reduced ATP production, electron transport efficiency, and proliferative capacity. These impairments were coupled with alterations in mitochondrial DNA content and expression of genes associated with ECM remodeling, mitochondrial energy metabolism, and apoptosis.</p><p>Study 3: Descriptive transcriptome analysis of tendon derived fibroblasts following <i>in vitro</i> exposure to advanced glycation end products. Rat Achilles tendon fibroblasts were treated with glycolaldehyde-derived AGEs (200μg/ml) for 48 hours in normal glucose (5.5mM) conditions. Total RNA was isolated and the PolyA⁺library was sequenced. We demonstrate that tendon fibroblasts treated with 200μg/ml of AGEs differentially express 2,159 gene targets compared to fibroblasts treated with an equal amount of bovine serum albumin (BSA)-Control. Our findings suggest that AGEs disrupt the tendon fibroblast transcriptome on a large scale and that these pathways may contribute to the development and progression of diabetic tendinopathy.</p><p>Study 4: Evaluation of tendon healing in a mouse model of elevated serum advanced glycation end products following tendon injury. Mice received daily BSA-Control or AGE-BSA injections (200μg/ml) for two weeks prior to creation of a tendon injury in the central third of both patellar tendons. Animals assigned to an exercise group began a moderate treadmill protocol (13 meters/min, five days/week, five weeks) one week following injury and all animals continued to receive injections until termination. We demonstrated that based on our injection dose and schedule, that serum AGEs are significantly elevated to ~200μg/ml, levels that are typically seen in type II diabetic patients. Additionally, a main effect for AGEs was observed in genes related to cell proliferation (Mybl2), mitochondrial function (Bcs1l), and growth factors (Fgf2). However, moderate treadmill exercise did not alter gene markers, such as Ctgf and Fgf2, which are makers of a tendon healing response. Our findings suggest that AGEs modulate tendon gene expression following patellar tendon injury, with no effect of moderate treadmill exercise.</p><p>Study 5: Serum levels of advanced glycation end products and their relationship to patellar tendon properties in diabetes. Subjects (n=32) from a full spectrum of diabetes status, including no history of diabetes were recruited for a cross-sectional study. A fasted blood sample was collected and magnetic resonance imaging (MRI) of the knee was completed. Both current HbA1c and previous diagnosis was used to stratify collected data. Additionally, a full correlation matrix of all measured variables was created to establish relationships that could be used to predict tendon pathology in diabetes. Our findings demonstrate that diabetes is associated with smaller patellar tendon dimensions, which is in disagreement with the literature. Further, we show that changes to body weight normalized (BWN) tendon cross-sectional area (CSA) occur independent of circulating N^ε-(carboxymethyl)lysine (CML) levels. These new data suggest that alternative mechanisms contributing to tendon pathology in diabetes deserve attention.</p>

Achilles tendinopathy is a debilitating condition affecting the entire spectrum of society and a condition that increases the risk of tendon rupture. Effective therapies remain elusive, as anti-inflammatory drugs and surgical interventions show poor long-term outcomes. Eccentric loading of the Achilles muscle-tendon unit is an effective physical therapy for treatment of symptomatic human tendinopathy. Post-injury analgesia is often achieved with non-steroidal anti-inflammatory drugs such as ibuprofen; however, there is increasing evidence that NSAID usage may interfere with the healing process. The deposition of aggrecan/hyaluronan (HA)-rich matrix within the tendon body and surrounding peritenon impede tendon healing and result in compromised biomechanical properties. Herein, we present work investigating chemical, biological, and mechanical loading approaches to treating Achilles tendinopathy in a murine model. Our previously established TGF-ß1-induced murine model of Achilles tendinopathy was used to investigate the cellular mechanism by which ibuprofen (chemical) therapy might lead to a worsening of tendon pathology, potentially by interfering with the native inflammation phase of tendon healing. We conclude that the use of ibuprofen for pain relief during inflammatory phases of tendinopathy has detrimental effects on the turnover of a pro-inflammatory HA matrix produced ain response to soft-tissue injury, thus preventing the switch to cellular responses associated with functional matrix remodeling and eventual healing. We examined the therapeutic potential of a recombinant human hyaluronidase, rHuPH20 (biologic, FDA approved for reducing HA accumulation in tumors) in a novel Achilles tendinopathy and retrocalcaneal bursitis injury model. The potential of rHuPH20 to effectively clear the pro-inflammatory, HA-rich matrix within the retrocalcaneal bursa (RCB) and tendon strongly supports the future refinement of injectable glycosidase preparations as potential treatments to protect or regenerate tendon tissue by reducing inflammation and scarring in the presence of bursitis or other inducers of damage such as mechanical overuse. Finally, we developed a novel mouse model of hind limb muscle loading (mechanical) designed to achieve a tissue-targeted therapeutic exercise. When applied to a murine Achilles tendinopathy model, muscle loading led to a significant improvement in Achilles tendon biomechanical outcome measures, with a decrease in cross-sectional area and an increase in material properties, compared to untreated animals. Our model facilitates the future investigation of mechanisms whereby rehabilitative muscle loading promotes healing of Achilles tendon injuries. Overall, these findings enhance our understanding of the mechanisms of injury and treatment in Achilles tendinopathy injuries. / Doctor of Philosophy / Achilles tendinopathy is a chronic, overuse condition affecting the entire spectrum of society and a condition that increases the risk of tendon rupture. Therapies are limited, as anti-inflammatory drugs and surgical interventions show poor long-term outcomes. Drugs such as ibuprofen are commonly prescribed at the onset of injury to treat pain. Eccentric loading of the Achilles muscle-tendon unit is an effective physical therapy for treatment of human tendinopathy; however, the reasons driving the healing are not well understood. Characteristics of the disease include pain, increased tendon size, and disorganization of tendon fiber structure. Here, we present work investigating chemical, biological, and mechanical loading approaches to treating Achilles tendinopathy in a mouse model. Our mouse model of Achilles tendinopathy was used to investigate how ibuprofen (chemical) therapy might lead to a worsening of tendon by potentially interfering with the inflammation phase of tendon healing. We conclude that the use of ibuprofen for pain relief during inflammatory phases of tendinopathy has negative effects on the turnover of matrix produced in response to injury, affecting the transition to the next phase in the tendon healing response. We examined the potential of a recombinant human hyaluronidase, rHuPH20 (biologic, FDA approved for reducing HA accumulation in tumors) in a novel Achilles tendinopathy and retrocalcaneal bursitis injury model. The potential of rHuPH20 to effectively clear the proinflammatory, HA-rich matrix within the retrocalcaneal bursa (RCB) and tendon strongly supports the future refinement of injectable treatments as a potential to protect or regenerate tendon tissue by reducing inflammation and scarring in the presence of bursitis or other inducers of damage such as mechanical overuse. Finally, we developed a mouse model of hind limb muscle loading (mechanical) based on physical therapy exercises. This model led to an improvement in biomechanical measures compared to untreated animals. The model allows for investigation of the underlying mechanisms in which physical therapy promotes healing of Achilles tendon injuries. Overall, these findings enhance our understanding of the mechanisms of injury and treatment in Achilles tendinopathy injuries.