Healthy Tendon Research Articles

TRP-CHANNELS IN TENDONS: FIRST INSIGHTS, NOVEL QUESTIONS

Tendinopathy is a disease associated with pain and tendon degeneration, leading to a decreased range of motion and an increased risk of tendon rupture. The etiology of this frequent disease is still unknown. In other musculoskeletal tissues like cartilage and intervertebral discs, transient receptor potential channels (TRP- channels) were shown to play a major role in the progression of degeneration. Due to their responsiveness to a wide range of stimuli like temperature, pH, osmolarity and mechanical load, they are potentially relevant factors in tendon degeneration as well. We therefore hypothesize that TRP- channels are expressed in tendon cells and respond to degeneration inducing stimuli.By immunohistochemistry, qRT-PCR and western blot analyses, we found three TRP channel members, belonging to the vanilloid (TRPV), and ankyrin (TRPA) subfamily, respectively, to be expressed in healthy human tendon tissue as well as in rodent tendon, with expression being located to cells within the dense tendon proper, as well as to endotenon resident cells. In vitro-inflammatory and ex vivo-mechanical stimulation led to a significant upregulation of TRPA1 expression in tendon cells, which correlates well with the fact that TRPA1 is considered as mechanosensitive channel being sensitized by inflammatory mediators.This is the first description of TRP- channels in human and rodent tendon. As these channels are pharmacologically targetable by both agonists and antagonists, they may represent a promising target for novel treatments of tendinopathy.

PLATELET-DERIVED EXTRACELLULAR VESICLES PROMOTE STEM CELL TENOGENIC COMMITMENT IN A BIOENGINEERED TENDON 3D MODEL

Worldwide, tendon disorders are one of the main causes of disability that decrease the quality of life of individuals and represent a substantial economic burden on society. Currently, the main therapies used for tendon injuries are not able to restore tendon functionality, and due to tendons' hypovascular and hypocellular nature, they present a reduced healing capacity, which also limits the success of the available therapies. In order to discover new therapies, extracellular vesicles (EVs), key players in cell-cell communication, have been widely explored for tissue engineering and regenerative medicine applications. Thus, the aim of this study is to assess the role of EVs derived from platelets in stem cell tenogenic commitment using a bioengineered tendon in vitro model for potential use as tendon therapeutic agents. Biomimetic platelet-derived EVs were produced by freeze-thaw cycles of platelets and isolation at different centrifugation speed. To recreate the architecture of tendons, a 3D system consisting of electrospun anisotropic nanofiber scaffolds coated with collagen encapsulating human adipose stem cells (hASCs) and different types of platelet-derived EVs, were produced. Then, the influence of the tendon-mimetic constructs and the distinct EVs populations in the hASCs tenogenic differentiation were assessed over culture time. We observed that the hASCs on the nanofibrous tendon scaffolds, show high cytoskeleton anisotropic organization that is characteristic of tenocytes. Moreover, acting as biological cues, platelet-derived EVs boosted hASCs tenogenic commitment, supported by the increased gene expression of tendon-related markers (SCX and TNMD). Additionally, EVs enhanced the deposition of tendon like extracellular matrix (ECM), as evidenced by the increased gene expression of ECM-related markers such as COL1, COL3, DCN, TNC, and MMP-3, which are fundamental for ECM synthesis and degradation balance. Moreover, EVs induced lower collagen matrix contraction on hASCs, which has been related with lower myofibroblast differentiation. Overall, the results revealed that EVs are capable of modulating stem cells' behavior boosting their tenogenic commitment, through the increased expression of healthy tendon cell markers, potentiating ECM deposition and decreasing cell contractility. Therefore, platelet EVs are a promising biochemical tool, worthy to be further explored, as paracrine signaling that might potentiate tendon repair and regeneration.

TENDON HEALTH AND DISEASE: EXPLORING THE INTERFASCICULAR NICHE

Tendon injury is debilitating and recalcitrant. With limited knowledge of disease aitiology we have are lacking in effective treatments for this prevalent musculoskeletal complaint.This presentation will outline our findings over the past few years in which we have demonstrated the importance of the interfascicular matrix (IFM) niche in maintaining healthy tendon function and driving disease progression1,2. It will also continue to describe our progress in developing both in vivo and in vitro models to interrogate disease progression.We have developed and validated a rat Achilles tendon overload model, in order to explore the impact of loading on IFM and fascicle structure, and the resulting cell response. Data highlights that structural disruption and inflammatory response both initiate in the IFM region, and can be seen in the absence of demonstrable changes to animal gait, indicating a sub-injury response in the tendon which we hypothesis may drive increased matrix turnover and repair3.We are now looking to interrogate the pathways driving this inflammatory behaviour in an organ-chip model, exploring the interplay between IFM cells and cells within fascicles. We have demonstrated phenotypic distinction of cells from the two niche environments, localized the progenitor phenotype to the IFM region and demonstrated significant mechanosensitivity in the IFM cell population4. We are currently building appropriate niche environments to maintain cell phenotype in our in vitro models, to explore the metabolic changes associated with disease progression.Acknowledgements: This body of work has received funding from: BBSRC (BB/K008412 /1); Versus Arthritis (project grant 20262); Horserace Betting Levy Board (T5); Dunhill Medical Charity (project grant RPGF1802\23); MRC (MR/T015462/1).

The Delayed Presentation of Achilles Tendon Ruptures Is Associated With Marked Alterations in the Gene Expression of COL1A1, MMPs, TIMPs, and IL-6

Background: Both acute and chronic Achilles tendon ruptures are affected by alterations in the extracellular matrix during the healing process of the tendon. Yet, these alterations in gene expression patterns are not well characterized. Purpose: To characterize temporal and spatial differences in gene expression patterns after an Achilles tendon rupture and to evaluate if cells from chronic Achilles tendon ruptures have the same ability to form new tendon tissue (tendon constructs) as healthy tendon cells. Study Design: Controlled laboratory study. Methods: A total of 35 patients with surgically treated Achilles tendon ruptures were included in the study and divided into 3 groups: acute (<4 weeks), short-term chronic (1-6 months), and long-term chronic (>6 months). Biopsy specimens were collected during surgical repair and were used to analyze the gene expression within the different groups and to compare mRNA levels in the proximal and distal tendon ends. A complementary in vitro experiment was performed to evaluate if cells from chronic Achilles tendon ruptures can form tendon constructs. Results: The mRNA levels for COL1A1 and COL3A1 were significantly higher in the short-term chronic group compared with the acute group (P < .05). Both MMP-1 and MMP-13 had the highest mRNA levels in the acute group (P < .01) compared with the long-term chronic group, while MMP-2 had the highest mRNA level in the short-term chronic group. Significant differences between the proximal and distal tendon ends were only detected for the monocyte and macrophage marker CD163 (P < .05), which was more expressed proximally. Cells extracted from chronic Achilles tendon ruptures displayed a similar ability and effectiveness to form tendon constructs as healthy tendon cells. Conclusion: A high collagenase gene activity after an Achilles tendon rupture indicated possible rapid matrix degradation in the acute phase. Chronic ruptures appeared to initiate the healing process even before treatment, indicated by the higher expression of collagen in the short-term chronic group. Cells from chronic Achilles tendon ruptures also displayed an ability to form new tendon tissue in vitro. Clinical Relevance: The study shows a rapid increase in collagenase gene expression, which could lead to matrix degradation that continues for months after an Achilles tendon rupture.

Measuring Ultrasonographic Thickness of the Achilles Tendon Insertion Is Less Reliable Than the Midportion in Healthy Tendons and Patients With Tendinopathy.

Ultrasound is the preferred imaging method in the diagnostic process of Achilles tendinopathy (AT). Ultrasound tissue characterization (UTC) is a frequently used, standardized and valid method to assess tendon geometry in AT patients. It is unknown whether UTC is reliable for measuring Achilles tendon thickness. The aim of the study was to assess intra- and inter-rater reliability of Achilles tendon thickness measurements using UTC in both asymptomatic individuals and patients with AT, and to evaluate if the reliability of thickness measurements differs between the midportion and insertional area. Exactly 50 patients with AT and 50 asymptomatic individuals were included. Using the conventional US and standardized UTC procedure maximum thickness was measured in the midportion and insertion region. To determine inter- and intra-rater reliabilities, the intraclass correlation coefficient (ICC) was used. The ICC values for inter- and intra-rater reliability were classified as "excellent," for the AT group (0.93 [95% CI: 0.88-0.96] and 0.95 [0.92-0.97]) and asymptomatic participants (0.91 [0.87-0.94] and 0.94 [0.92-0.96]). The reliability of measuring tendon thickness in the midportion region was "excellent," with both inter-rater (0.97 [0.95-0.98]) and intra-rater (0.98 [0.96-0.99]) ICC values indicating high levels of agreement. In the insertional region, ICC values for inter-rater (0.79 [0.69-0.87]) and intra-rater (0.89 [0.84-0.93]) reliability were "moderate to good." We showed excellent reliability for measuring the US thickness of the midportion and good reliability of measuring the insertional region in patients with AT. Significantly lower ICCs were observed for the reliability of thickness measurements in the insertional region when compared with the midportion.

An automated method for tendon image segmentation on ultrasound using grey-level co-occurrence matrix features and hidden Gaussian Markov random fields

Background:Despite knowledge of qualitative changes that occur on ultrasound in tendinopathy, there is currently no objective and reliable means to quantify the severity or prognosis of tendinopathy on ultrasound. Objective:The primary objective of this study is to produce a quantitative and automated means of inferring potential structural changes in tendinopathy by developing and implementing an algorithm which performs a texture based segmentation of tendon ultrasound (US) images. Method:A model-based segmentation approach is used which combines Gaussian mixture models, Markov random field theory and grey-level co-occurrence (GLCM) features. The algorithm is trained and tested on 49 longitudinal B-mode ultrasound images of the Achilles tendons which are labelled as tendinopathic (24) or healthy (25). Hyperparameters are tuned, using a training set of 25 images, to optimise a decision tree based classification of the images from texture class proportions. We segment and classify the remaining test images using the decision tree. Results:Our approach successfully detects a difference in the texture profiles of tendinopathic and healthy tendons, with 22/24 of the test images accurately classified based on a simple texture proportion cut-off threshold. Results for the tendinopathic images are also collated to gain insight into the topology of structural changes that occur with tendinopathy. It is evident that distinct textures, which are predominantly present in tendinopathic tendons, appear most commonly near the transverse boundary of the tendon, though there was a large variability among diseased tendons. Conclusion:The GLCM based segmentation of tendons under ultrasound resulted in distinct segmentations between healthy and tendinopathic tendons and provides a potential tool to objectively quantify damage in tendinopathy.

Management of Patellar Tendinopathy

Patellar tendinopathy is a common pathology typically seen in athletes involved in repetitive explosive jumping and running activities. Also known as jumpers’ knee, it is commonly seen in high-level basketball players. Typically, athletes continue to play with symptoms, which can be aggravated and progress to partial patellar tendon tears. When partial patellar tendon tears occur, prolonged recovery and decreased performance is commonly seen. The pathology and treatment can be frustrating for both the athlete and medical provider. Patellar tendinopathy typically does not involve inflammation but rather microinjury to the tendon fibers, which leads to mucoid degeneration, necrosis, and loss of transitional fibrocartilage. When partial tendon tears do occur, the typical location is posteromedially adjacent to the patella. Treatment involves a stepwise approach starting with nonoperative means, including activity modification, nonsteroidal anti-inflammatories, and physical therapy focused on eccentrics. Extracorporeal shock wave treatments and injections with platelet-rich plasma or bone marrow aspirate concentrate should be considered, with evolving literature to support their use. Ultrasound percutaneous tendon scrapping with a needle supplemented with the aforementioned injections is an emerging treatment option that the authors have found to be helpful, although further studies are required. Surgical intervention is considered after failure of nonoperative treatments, and typically occurs in tears greater than 50% of the tendon thickness and in tendons with increased thickness (>8.8 mm). Open or arthroscopic debridement can be considered, with no studies showing superior outcomes with either technique; however, no high-quality comparison studies exist. The authors prefer an open technique where, much like a bone–patellar tendon–bone harvest, the unhealthy proximal tendon and bone are excised with then closure of the healthy tendon with absorbable sutures. Suture anchor repair may also be used when necessary. In a recent systematic review, surgical management of patellar tendinopathy has been shown to result in improved patient-reported outcomes with return to sport at high levels.1 Treatment for the difficult and sometimes frustrating pathology of patellar tendinopathy continues to evolve, with biologic and less-invasive ultrasound-based treatments showing promise, and surgical intervention providing reliable outcomes.

Murine Hind Limb Explant Model for Studying the Mechanobiology of Achilles Tendon Impingement.

Tendon impingement upon bone generates a multiaxial mechanical strain environment with markedly elevated transverse compressive strain, which elicits a localized fibrocartilage phenotype characterized by accumulation of glycosaminoglycan (GAG)-rich matrix and remodeling of the collagen network. While fibrocartilage is a normal feature in impinged regions of healthy tendons, excess GAG deposition and disorganization of the collagen network are hallmark features of tendinopathy. Accordingly, impingement is clinically recognized as an important extrinsic factor in the initiation and progression of tendinopathy. Nevertheless, the mechanobiology underlying tendon impingement remains understudied. Prior efforts to elucidate the cellular response to tendon impingement have applied uniaxial compression to cells and excised tendon explants in vitro. However, isolated cells lack a three-dimensional extracellular environment crucial to mechanoresponse, and both in vitro and excised explant studies fail to recapitulate the multiaxial strain environment generated by tendon impingement in vivo, which depends on anatomical features of the impinged region. Moreover, in vivo models of tendon impingement lack control over the mechanical strain environment. To overcome these limitations, we present a novel murine hind limb explant model suitable for studying the mechanobiology of Achilles tendon impingement. This model maintains the Achilles tendon in situ to preserve local anatomy and reproduces the multiaxial strain environment generated by impingement of the Achilles tendon insertion upon the calcaneus during passively applied ankle dorsiflexion while retaining cells within their native environment. We describe a tissue culture protocol integral to this model and present data establishing sustained explant viability over 7 days. The representative results demonstrate enhanced histological GAG staining and decreased collagen fiber alignment secondary to impingement, suggesting elevated fibrocartilage formation. This model can easily be adapted to investigate different mechanical loading regimens and allows for the manipulation of molecular pathways of interest to identify mechanisms mediating phenotypic change in the Achilles tendon in response to impingement.

Spatial gene expression in the adult rat patellar tendon

Tendons are dense connective tissues with relatively few cells which makes studying the molecular profile of the tissue challenging. There is not a consensus on the spatial location of various cell types within a tendon, nor the accompanying transcriptional profile. In the present study, we used two male rat patellar tendon samples for sequencing-based spatial transcriptomics to determine the gene expression profile. We integrated our data with a mouse Achilles single cell dataset to predict the cell type composition of the patellar tendon as a function of location within the tissue. The spatial location of the predicated cell types suggested that there were two populations of tendon fibroblasts, one located in the tendon midsubstance, while the other localized with red blood cells, pericytes, and immune cells to the tendon peripheral connective tissue. Of the highest expressed spatially variable genes, there were multiple genes with known function in tendon: Col1a1, Col1a2, Dcn, Fmod, Sparc, and Comp. Further, a novel spatially regulated gene (AABR07000398.1) with no known function was identified. The spatial gene expression of tendon associated genes (Scx, Thbs4, Tnmd, Can, Bgn, Lum, Adamts2, Lox, Ppib, Col2a1, Col3a1, Col6a2) was also visualized. Both patellar tendon samples had similar expression patterns for all these genes. This dataset provides new spatial insights into gene expression in a healthy tendon.

ITRAQ-based proteomics reveals potential markers and treatment pathways for acute Achilles tendon rupture

BackgroundDue to its limited blood supply and irregular mechanical loading, the Achilles tendon is the most frequently ruptured tendon. Despite the rising incidence of acute Achilles tendon rupture (AATR), the optimal treatment remains controversial. Missed diagnoses and delayed treatments lead to poor outcomes and limited treatment options. This study aimed to identify potential biomarkers for diagnosing and developing therapies for AATR.MethodsWe employed the coupled isobaric tag for relative and absolute quantitation-liquid chromatography–electrospray ionization-tandem mass spectrometry approach to investigate protein expression in tissues from AATR patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify differentially expressed proteins (DEPs) between AATR patients and healthy individuals. A protein–protein interaction (PPI) network of DEPs was constructed using the Search Tool for the Retrieval of Interacting Genes. The screened hub genes were selectively verified by immunohistochemical staining.ResultsWe identified 410 DEPs between AATR patients and controls. The DEPs were significantly enriched in GO terms such as the extracellular region, extracellular region part, and defense response, as well as KEGG pathways, including complement and coagulation cascades, focal adhesion, and regulation of actin cytoskeleton. The main hub nodes in the PPI network comprised fibronectin 1 (FN1), major histocompatibility complex, class I, B (HLA-B), filamin A (FLNA), heat shock 27-kDa protein 1 (HSPB1), heat shock protein family A member 5 (HSPA5), apolipoprotein A4 (APOA4), and myosin IC (MYO1C). Although APOA4 and collagens I, II, and III were detectable in healthy tendons, immunohistochemical staining confirmed higher expression of these proteins in the acutely ruptured Achilles tendon.ConclusionsOur findings lay a foundation for further molecular studies of AATR. Inflammation and age-related degeneration may contribute to the pathogenesis of AATR. Moreover, the identified DEPs could be potential biomarkers for AATR diagnosis and treatment.

Neural-driven activation of 3D muscle within a finite element framework: exploring applications in healthy and neurodegenerative simulations

This paper presents a novel computational framework for neural-driven finite element muscle models, with an application to amyotrophic lateral sclerosis (ALS). The multiscale neuromusculoskeletal (NMS) model incorporates physiologically accurate motor neurons, 3D muscle geometry, and muscle fiber recruitment. It successfully predicts healthy muscle force and tendon elongation and demonstrates a progressive decline in muscle force due to ALS, dropping from 203 N (healthy) to 155 N (120 days after ALS onset). This approach represents a preliminary step towards developing integrated neural and musculoskeletal simulations to enhance our understanding of neurodegenerative and neurodevelopmental conditions through predictive NMS models.

Early Tendon Morphology as a Biomarker of Long-term Patient Outcomes After Surgical Repair of Achilles Tendon Rupture: A Prospective Cohort Study

Background: Patient outcome after acute Achilles tendon rupture (ATR) varies and is difficult to predict. Whether early variations in healing, visualized with ultrasonography, can predict long-term patient outcome is unclear. Purpose: To (1) examine the associations of Achilles tendon cross-sectional area (CSA) and elongation (TE) during healing of ATR repair with patient outcomes at 12 months postoperatively and (2) investigate the predictive or diagnostic capacity of the morphological biomarkers. Study Design: Cohort study; Level of evidence, 2. Methods: This study was based on previously collected data from 86 patients who underwent acute standardized ATR repair between 2013 and 2018 and who were included in a prior randomized trial investigating early functional mobilization (EFM). In the EFM group, loading was allowed immediately after surgery, while in the comparison group, loading was allowed first at 2 weeks postoperatively. Achilles tendon CSA and length were measured with ultrasound at 6 weeks, 6 months, and 12 months postoperatively. CSA ratio and absolute difference in the length of the healthy and injured tendons were calculated. Patient-reported outcome was registered with the validated Achilles tendon Total Rupture Score and functional outcome with the heel-rise endurance test at 12 months postoperatively. The limb symmetry index (LSI) was calculated for maximum heel-rise height (HRHmax) and total concentric work. Multiple linear regression adjusted for age was used, and the area under the receiver operating characteristic curve (AUC) was calculated to evaluate predictive capacity. Results: A larger CSA ratio at 6 weeks was associated with higher LSI HRHmax at 12 months ( R2, 0.35; P &lt; .001) and exhibited good predictive capacity (AUC, 0.82). More TE at 12 months was associated with lower LSI total concentric work at 12 months ( R2, 0.21; P = .001) and exhibited acceptable predictive capacity (AUC, 0.71). Conclusion: Greater Achilles tendon CSA seen on ultrasound 6 weeks after surgical repair had good clinical prediction for long-term functional outcome. TE at 12 months was predictive of inferior functional outcome. Registration: NCT02318472 (ClinicalTrials.gov identifier).

Infrared thermography in the diagnosis of Achilles tendinitis. A randomized double-blind pilot clinical trial

Background: The Achilles tendon (AT) is the widest and most resistant of the osteoarticular system and has the greatest load-bearing capacity. It is involved in daily functioning and sports activities performance. Exposure to excessive stress on the calcaneus tendon (CT) can prevent an effective repair process and favor permanent injuries. Tendinopathy is a clinical syndrome resulting from disorientation of AT fibers, and inflammatory signs characteristic of tendinitis or tissue degeneration present in tendinosis can be found. The condition can manifest itself through functional changes accompanied by clinical signs such as crackling, tenderness, pain and edema. Infrared thermography is used to trace thermographic profiles, capable of detecting thermal changes related to pathologies. Objectives: The main goal of this study was to correlate AT region thermograms with clinical and functional characteristics in healthy individuals with CT pathology. Methods: The present work consists of a double-blind pilot randomized trial, of qualitative and quantitative nature. Individuals with TC tendinopathy, classified in the Tendinopathy Group (TG) and individuals without tendinopathy, classified in the Control Group (CG) participated. Assessments were performed to characterize the subjects belonging to the TG and CG: anamnesis, infrared thermography, referred pain, crepitation and thickness on palpation, algometry, arch sign test and Royal London Hospital test, pain on passive dorsiflexion, pain on lifting the heel and long jump. Results: The results obtained in infrared thermography were consistent with those obtained in the clinical evaluation for TG and GC. The results demonstrate that healthy tendons presented an average temperature difference of 0.24 ± 0.15 ºC between legs with a maximal difference of 0.4 ºC. On the other hand, unilateral tendinopathy presented an average temperature difference of 1.2 ± 0.9 ºC, however, this difference could be as big as 5.1 ºC. Conclusion: It is concluded that infrared thermography can be used safely and non-invasively to aid in the diagnosis of Achilles tendon tendinopathy.

Detection and Quantitative Assessment of Arthroscopically Proven Long Biceps Tendon Pathologies Using T2 Mapping.

This study evaluates how far T2 mapping can identify arthroscopically confirmed pathologies in the long biceps tendon (LBT) and quantify the T2 values in healthy and pathological tendon substance. This study comprised eighteen patients experiencing serious shoulder discomfort, all of whom underwent magnetic resonance imaging, including T2 mapping sequences, followed by shoulder joint arthroscopy. Regions of interest were meticulously positioned on their respective T2 maps, capturing the sulcal portion of the LBT and allowing for the quantification of the average T2 values. Subsequent analyses included the calculation of diagnostic cut-off values, sensitivities, and specificities for the detection of tendon pathologies, and the calculation of inter-reader correlation coefficients (ICCs) involving two independent radiologists. The average T2 value for healthy subjects was measured at 23.3 ± 4.6 ms, while patients with tendinopathy displayed a markedly higher value, at 47.9 ± 7.8 ms. Of note, the maximum T2 value identified in healthy tendons (29.6 ms) proved to be lower than the minimal value measured in pathological tendons (33.8 ms), resulting in a sensitivity and specificity of 100% (95% confidence interval 63.1-100) across all cut-off values ranging from 29.6 to 33.8 ms. The ICCs were found to range from 0.93 to 0.99. In conclusion, T2 mapping is able to assess and quantify healthy LBTs and can distinguish them from tendon pathology. T2 mapping may provide information on the (ultra-)structural integrity of tendinous tissue, facilitating early diagnosis, prompt therapeutic intervention, and quantitative monitoring after conservative or surgical treatments of LBT.

Matrix stiffness-mediated tenogenesis of tendon stem/progenitor cells via integrin-αm for tendon regeneration

Tendon injuries, commonly associated with sports activities, pose significant challenges in terms of treatment and recovery due to limited tendon regeneration and the formation of proliferative scars. Stem cell-based therapy has shown promising application, but there are still challenges. Physical and biological cues are instrumental in guiding stem cell differentiation and maturation. This study focuses on exploring the effects of matrix biomechanics on tendon stem/progenitor cells (TSPCs) differentiation. We fabricated polydimethylsiloxane (PDMS) substrates with different elastic modulus to mimic the mechanical characteristics of healthy tendons. A tissue-engineered culture system was developed for tenogenesis, and pre-differentiated tissue-engineered tendons were transplanted in vivo to assess their efficacy in regenerating patella tendon injuries. Furthermore, we demonstrated that the biomechanical stimuli activated the integrin-αm to enhance the tenogenesis capacity of TSPCs. Our findings highlight the importance of biomechanics in tendon tissue engineering and provide a novel perspective for enhancing tendon regeneration.

A New Test for Achilles Tendinopathy Based on Kager's Fat Pad Clinical Assessment Predictive Values.

Observational study. Seventy patients recruited from a private medical centre met the diagnostic criteria for unilateral Achilles tendinopathy (age, 45.1 ± 12.7 years; weight, 75.00 ± 10 kg; height, 1.75 ± 0.1 m) and were tested based on both Achilles tendons. Seventy patients with a unilateral Achilles tendinopathy ultrasound diagnosis were tested using David's test. Most (86%) subjects demonstrated Kager's fat pad asymmetry in relation to the Achilles tendon in the complete passive dorsiflexion in the prone position (David's sign). No healthy tendons had David's sign. The presence of asymmetry in Kager's fat pad in relation to the Achilles tendon during complete passive dorsiflexion is strongly indicative of ultrasound-diagnosed tendinopathy. David's test demonstrated a sensitivity of 85.71% (95% CI, 77.51% to 93.91%) and a specificity of 100% (95% CI, 100% to 100%), while noting the lack of blinding of the assessors and the uncertainty of the diagnostic measures (95% CI). Asymmetry of the fat pad could potentially serve as a characteristic marker for patients with Achilles tendinopathy.

Ultrasonographic Finding of Contralateral Achilles Tendon in Patients With Acute Achilles Tendon Rupture: A Prospective Observational Study.

Although the incidence of contralateral Achilles tendon in patients with Achilles tendon rupture is higher than in the general population, there are no studies evaluating the status of the contralateral Achilles tendon. The aim of this study was to investigate the status of the contralateral Achilles tendon in patients with acute Achilles tendon rupture. Prospective observational cohort study. University hospital foot and ankle clinic. Seventy-five patients with acute Achilles tendon rupture who met the inclusion criteria. Ultrasonography performed by an orthopedic surgeon who had 8 years of experience in musculoskeletal ultrasonography. Ultrasonographic abnormalities of the contralateral Achilles tendon at the time of diagnosis of acute Achilles tendon rupture. Abnormalities were categorized as intratendinous lesions, peritendinous lesions, changes in retrocalcaneal bursa, and Achilles tendon thickening. The maximal Achilles tendon thickness had a mean of 4.8 ± 1.0 mm. Nine patients (12%) showed ultrasonographic abnormalities on the contralateral Achilles tendon, and the presence of exertional pain was the sole associating variable with ultrasonographic abnormalities. The prevalence of ultrasonographic abnormalities in the contralateral Achilles tendon shown in this study was not higher than that reported in healthy or asymptomatic Achilles tendon. Therefore, routine evaluation of the contralateral Achilles tendon is unnecessary at the time of acute Achilles tendon rupture.

Devices to measure calf raise test outcomes: A narrative review.

The calf raise test (CRT) is commonly administered without a device in clinics to measure triceps surae muscle function. To standardise and objectively quantify outcomes, researchers use research-grade or customised CRT devices. To incorporate evidence-based practice and apply testing devices effectively in clinics, it is essential to understand their design, applicability, psychometric properties, strengths, and limitations. Therefore, this review identifies, summarises, and critically appraises the CRT devices used in science. Four electronic databases were searched in April 2022. Studies that used devices to measure unilateral CRT outcomes (i.e., number of repetitions, work, height) were included. Thirty-five studies met inclusion, from which seven CRT devices were identified. Linear encoder (n=18) was the most commonly used device, followed by laboratory equipment (n=6) (three-dimensional motion capture and force plate). These measured the three CRT outcomes. Other devices used were electrogoniometer, Häggmark and Liedberg light beam device, Ankle Measure for Endurance and Strength (AMES), Haberometer, and custom-made. Devices were mostly used in healthy populations or Achilles tendon pathologies. AMES, Haberometer, and custom-made devices were the most clinician-friendly, but only quantified repetitions were completed. In late 2022, a computer vision mobile application appeared in the literature and offered clinicians a low-cost, research-grade alternative. This review details seven devices used to measure CRT outcomes. The linear encoder is the most common in research and quantifies all three CRT outcomes. Recent advances in computer-vision provide a low-cost research-grade alternative to clinicians and researchers via a n iOS mobile application.

Ultrasound Measurement of Local Deformation in the Human Free Achilles Tendon Produced by Dynamic Muscle-Induced Loading: A Systematic Review

Achilles tendinopathy is the most prevalent lower limb tendinopathy, yet it remains poorly understood, with mismatches between observed structure and reported function. Recent studies have hypothesised that Achilles tendon (AT) healthy function is associated with variable deformation across the tendon width during use, focusing on quantifying sub-tendon deformation. Here, the aim of this work was to synthesise recent advances exploring human free AT tissue-level deformation during use. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, PubMed, Embase, Scopus and Web of Science were systematically searched. Study quality and risk of bias were assessed. Thirteen articles were retained, yielding data on free AT deformation patterns. Seven were categorised as high-quality and six as medium-quality studies. Evidence consistently reports that healthy and young tendons deform non-uniformly, with the deeper layer displacing 18%-80% more than the superficial layer. Non-uniformity decreased by 12%-85% with increasing age and by 42%-91% in the presence of injury. There is limited evidence of large effect that AT deformation patterns during dynamic loading are non-uniform and may act as a biomarker of tendon health, risk of injury and rehabilitation impact. Better considered participant recruitment and improved measurement procedures would particularly improve study quality, to explore links between tendon structure, function, aging and disease in distinct populations.

Achilles Tendon Tissue Turnover Before and Immediately After an Acute Rupture

Background: An Achilles tendon rupture (ATR) is a frequent injury and results in the activation of tendon cells and collagen expression, but it is unknown to what extent turnover of the tendon matrix is altered before or after a rupture. Purpose/Hypothesis: The purpose of this study was to characterize tendon tissue turnover before and immediately after an acute rupture in patients. It was hypothesized that a rupture would result in pronounced collagen synthesis in the early phase (first 2 weeks) after the injury. Study Design: Cross-sectional study; Level of evidence, 3. Methods: The study included patients (N = 18) eligible for surgery after an ATR. At the time of inclusion, the patients ingested deuterium oxide (2H2O) orally, and on the day of surgery (within 14 days of the injury), they received a 3-hour flood-primed infusion of an 15N-proline tracer. During surgery, the patients had 1 biopsy specimen taken from the ruptured part of the Achilles tendon and 1 that was 3 to 5 cm proximal to the rupture as a control. The biopsy specimens were analyzed for carbon-14 (14C) levels in the tissue to calculate long-term turnover (years), incorporation of 2H-alanine (from 2H2O) into the tissue to calculate the fractional synthesis rate (FSR) of proteins in the short term (days), and incorporation of 15N-proline into the tissue to calculate the acute FSR (hours). Results: Both the rupture and the control samples showed consistently lower levels of 14C compared with the predicted level of 14C in a healthy tendon, which indicated increased tendon turnover in a fraction (48% newly synthesized) of the Achilles tendon already for a prolonged period before the rupture. Over the first days after the rupture, the synthesis rate for collagen was relatively constant, and the average synthesis rate on the day of surgery (2-14 days after the rupture) was 0.025% per hour, irrespective of the length of time after a rupture and the site of sampling (rupture vs control). No differences were found in the FSR between the rupture and control samples in the days after the rupture. Conclusion: Higher than normal tissue turnover in the Achilles tendon before a rupture indicated that changes in the tendon tissue preceded the injury. In addition, we observed no increase in tendon collagen tissue turnover in the first 2 weeks after an ATR. This favors the view that an increase in the formation of new tendon collagen is not an immediate phenomenon during the regeneration of ruptured tendons in patients. Registration: NCT03931486 (ClinicalTrials.gov identifier).