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Objective: To assess the mechanism of supraspinatus tendinopathy induced by type 2 diabetes mellitus (T2DM) in rats using untargeted metabolomics analysis., Methods: The liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics approach was used to screen tendon biomarkers of supraspinatus tendinopathy in rats with T2DM. Seventy-eight Sprague-Dawley rats were divided into normal group (NG) and T2DM groups. Rats in T2DM groups were divided into 12-week (T2DM-12w), and 24-week (T2DM-24w) subgroups according to the time point of the establishment of the T2DM rat model. Histological evaluation (modified Bonar score) and biomechanical testing were used to analyze the adverse effects of type 2 diabetes on the tendon of the supraspinatus muscle in rats.Three comparable groups were set up, including T2DM-12w group vs. NG, T2DM-24w group vs. NG, and T2DM-24w group vs. T2DM-12w group. Differentially expressed metabolites (DEMs) in the supraspinatus tendons in the three groups of rats were analyzed using LC-MS, and data were analyzed using multivariate statistical methods to screen potential biomarkers. The DEMs included in the intersection of the three groups were identified as those associated with the development of diabetic supraspinatus tendinopathy, and trend analysis and pathway topology analysis were performed., Results: With the progression of diabetes, the tendinopathy of the supracinatus muscle of diabetic rats gradually intensified, mainly manifested as inflammatory reactions, disordered collagen fibers, fat infiltration, and increased modified Bonar score. The intersection of DEMs among the three comparable groups was resulted in the identification of 10 key DEMs, in which melezitose and raffinose showed a continuous increasing trend with the prolongation of disease course. By pathway topology analysis, 10 DEMs (P < 0.01) were mainly associated with the pathways of galactose metabolism, which could be involved in the development of diabetes-induced supraspinatus tendinopathy., Conclusion: T2DM causes tendinopathy of the supraspinatus muscle in rats. 10 key DEMs obtained by untargeted metabolomics assay suggested that the development of diabetes-induced supraspinatus tendinopathy was associated with changes in metabolic pathways, such as galactose metabolism. melezitose and raffinose hold promise as a biomarker for disease discrimination and/or disease indication in diabetic supraspinatus tendinopathy., Competing Interests: Declarations Ethics approval and consent to participate This study was carried out in accordance with NIH guidelines for the care and use of laboratory animals (8th edition, NIH). The study protocol was approved by the Ethics Committee of Experimental Animals of the Affiliated Hospital of Qingdao University (Approval No. 20220505SD8020221210126). All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The methods are reported in accordance with ARRIVE guidelines (https://arriveguidelines.org) for the reporting of animal experiments. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Achilles tendinopathy is often attributed to overuse, but its pathophysiology remains poorly understood. Disruption to the molecular structure of collagen is fundamental for the onset and progression of tendinopathy but has mostly been investigated in vitro. Here, we interrogated the in vivo molecular structure changes of collagen in rat Achilles tendons following treadmill running. Unexpectedly, the tendons' collagen molecules were not mechanically unfolded by running but denatured through proteolysis during physiological post-run remodeling. We further revealed that running induces inflammatory gene expressions in Achilles tendons and that long-term running causes prolonged, elevated collagen degradation, leading to the accumulation of denatured collagen and tendinopathy development. For applications, we demonstrated magnetic resonance imaging of collagenase-induced Achilles tendon injury in vivo using a denatured collagen targeting contrast agent. Our findings may help close the knowledge gaps in the mechanobiology and pathogenesis of Achilles tendinopathy and initiate new strategies for its imaging-based diagnosis.

Tendon calcification is a common clinical condition that frequently occurs as a complication after tendon injury and surgery, or as an expression of fibrodysplasia ossificans progressiva. This condition can be referred to by various names in clinical practice and literature, including tendon ossification, tendon mineralization, heterotopic ossification, and calcific tendonitis. The exact pathogenesis of tendon calcification remains uncertain, but current mainstream research suggests that calcification is mostly cell mediated. To further elucidate the pathogenesis of tendon calcification and to better simulate the overall process, selecting appropriate experimental animal models is important. Numerous animal models have been utilized in various clinical studies, each with its own set of advantages and limitations. In this review, we have discussed the advancements made in research on animal models of tendon calcification, with a focus on the selection of experimental animals, the sites of injury in these models, and the methods employed for modeling., (© 2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Achilles tendinopathy (TP) is characterized as the third most common disease of the musculoskeletal system, and occurs in three phases. There is currently no evidence of effective treatment for this medical condition. In this study, the modulatory effects of the minimally invasive technique intratissue percutaneous electrolysis (EPI) and combinations of EPI with four nutritional factors included in the diet, hydroxytyrosol (HT), maslinic acid (MA), glycine, and aspartate (AA), on hepatic intermediary metabolism was examined in Wistar rats with induced tendinopathy at various stages of TP. Results obtained showed that induced tendinopathy produced alterations in the liver intermediary metabolisms of the rats. Regarding carbohydrate metabolism, a reduction in the activity of pro-inflammatory enzymes in the later stages of TP was observed following treatment with EPI alone. Among the combined treatments using nutritional factors with EPI, HT+EPI and AA+EPI had the greatest effect on reducing inflammation in the late stages of TP. In terms of lipid metabolism, the HT+EPI and AA+EPI groups showed a decrease in lipogenesis. In protein metabolism, the HT+EPI group more effectively reduced the inflammatory effects of induced TP. Treatment with EPI combined with nutritional factors might help regulate intermediary metabolism in TP disease and reduce the inflammation process.

This review is an update of a previous systematic review and assesses the evidence for the association of work-related physical and psychosocial risk factors and specific disorders of the shoulders. Medline, Embase, Web of Science Core Collection, Cochrane Central and PsycINFO were searched and study eligibility and risk of bias assessment was performed by two independent reviewers. A total of 14 new articles were added with the majority focusing on rotator cuff syndrome (RCS) with seven studies. Nine articles reported psychosocial exposures in addition to physical exposures. The strongest evidence was found for the association between elevation, repetition, force and vibration and the occurrence of SIS and tendinosis/tendonitis. Evidence also suggests that psychosocial exposures are associated with the occurrence of RCS and tendinosis/tendonitis. Other findings were inconsistent which prevents drawing strong conclusions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study aimed to examine the association between calcific rotator cuff tendinopathy (RCT) and nephrolithiasis and/or cholelithiasis. A case-control study was conducted on patients diagnosed with RCT between June 2016 and June 2022. RCT was confirmed by ultrasound, and patients were divided into 2 groups: calcific RCT (case) and non-calcific RCT (control). Data were collected retrospectively from electronic medical records and completed by phone calls, looking for a history of nephrolithiasis and/or cholelithiasis; based on clinical features or incidental findings on abdominal and pelvic imaging. A total of 210 patients with RCT were included. Among the 95 cases of calcific RCT, 43 had a history of lithiasis (45.3%) against 23 (20%) from the non-calcific RCT group (P < .001); 21 patients suffered from nephrolithiasis (22.1%) and 26 had cholelithiasis (27.4%) versus 10 (8.7%) (P = .006) and 16 (13.9%) (P = .015) in the non-calcific RCT group, respectively. Logistic regression showed that the independent predictors of calcific RCT included a history of nephrolithiasis (OR, 4.38; 95% CI: 1.61-11.92, P = .004) and a history of cholelithiasis (OR, 3.83; 95% CI: 1.64-8.94, P = .002). In patients with calcific RCT, the occurrence of lithiasis was significantly associated in the bivariate analysis with higher age, body mass index, fasting blood sugar, and HbA1c (all with P < .05), but only with the presence of another site of calcific tendinopathy than the shoulder (OR, 3.11; 95% CI: 1.12-8.65, P = .03) in the multivariate analysis. Nephrolithiasis and/or cholelithiasis are associated with calcific RCT, and their presence predicts calcific RCT at least 3 times. Further research is required to determine the common risk factors and preventive measures against lithogenesis in patients with calcific RCT, nephrolithiasis, and cholelithiasis., Competing Interests: The authors have no funding and no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Tendinopathy is one of the most common musculoskeletal diseases, and mechanical overload is considered its primary cause. However, the underlying mechanism through which mechanical overload induces tendinopathy has not been determined. In this study, we identified for the first time that tendon cells can release extracellular mitochondria (ExtraMito) particles, a subtype of medium extracellular particles (mEPs), into the environment through a process regulated by mechanical loading. RNA sequencing systematically revealed that oxygen-related reactions, extracellular particles, and inflammation were present in diseased human tendons, suggesting that these factors play a role in the pathogenesis of tendinopathy. We simulated the disease condition by imposing a 9% strain overload on three-dimensional mouse tendon constructs in our cyclic uniaxial stretching bioreactor. The three-dimensional mouse tendon constructs under normal loading with 6% strain exhibited an extended mitochondrial network, as observed through live-cell confocal laser scanning microscopy. In contrast, mechanical overload led to a fragmented mitochondrial network. Our microscopic and immunoblot results demonstrated that mechanical loading induced tendon cells to release ExtraMito particles. Furthermore, we showed that mEPs released from tendon cells overloaded with a 9% strain (mEP 9% ) induced macrophage chemotaxis and increased the production of proinflammatory cytokines, including IL-6, CXCL1, and IL-18, from macrophages compared to mEP 0% , mEP 3% , and mEP 6% . Partial depletion of the ExtraMito particles from mEP 9% by magnetic-activated cell sorting significantly reduced macrophage chemotaxis. N-acetyl-L-cysteine treatment preserved the mitochondrial network in overloaded tendon cells, diminishing overload-induced macrophage chemotaxis toward mEP 9% . These findings revealed a novel mechanism of tendinopathy; in an overloaded environment, ExtraMito particles convey mechanical response signals from tendon cells to the immune microenvironment, culminating in tendinopathy., (© 2024. The Author(s).)

Introduction: Calcific tendinosis is a common condition caused by the deposition of hydroxyapatite crystals within the tendons that can impact any tendinous insertion. In this situation, ultrasound (US) may be a viable imaging modality in addition to radiography., Case Presentation: A 56-year-old Iranian male presented with left elbow pain. US evaluation at the lump site revealed a subcutaneous lipoma. Ultrasonography showed a thickened and diffusely heterogeneously hypoechoic pronator teres tendon. These characteristics were consistent with the diagnosis of calcific tendinosis., Discussion and Conclusion: Radiography is the most common and practical imaging modality for calcific tendinosis diagnosis. Despite this, the real-time nature of ultrasonography makes it both diagnostic and therapeutic in this condition. Other conditions, such as lipoma, may interfere with the proper diagnosis of calcific tendinosis., (© 2024. The Author(s).)

Patellar tendinopathy is a common clinical problem, but its underlying pathophysiology remains poorly understood, primarily due to the absence of a representative experimental model. The most widely used method to generate such a model is collagenase injection, although this method possesses limitations. We developed an optimized rat model of patellar tendinopathy via the ultrasound-guided injection of collagenase mixed with a thermo-responsive Pluronic hydrogel into the patellar tendon of sixty male Wistar rats. All analyses were carried out at 3, 7, 14, 30, and 60 days post-injury. We confirmed that our rat model reproduced the pathophysiology observed in human patients through analyses of ultrasonography, histology, immunofluorescence, and biomechanical parameters. Tendons that were injured by the injection of the collagenase-Pluronic mixture exhibited a significant increase in the cross-sectional area ( p < 0.01), a high degree of tissue disorganization and hypercellularity, significantly strong neovascularization ( p < 0.01), important changes in the levels of types I and III collagen expression, and the organization and presence of intra-tendinous calcifications. Decreases in the maximum rupture force and stiffness were also observed. These results demonstrate that our model replicates the key features observed in human patellar tendinopathy. Collagenase is evenly distributed, as the Pluronic hydrogel prevents its leakage and thus, damage to surrounding tissues. Therefore, this model is valuable for testing new treatments for patellar tendinopathy.

Tendinopathy (TP) is a complex clinical syndrome characterized by local inflammation, pain in the affected area, and loss of performance, preceded by tendon injury. The disease develops in three phases: Inflammatory phase, proliferative phase, and remodeling phase. There are currently no proven treatments for early reversal of this type of injury. However, the metabolic pathways of the transition metabolism, which are necessary for the proper functioning of the organism, are known. These metabolic pathways can be modified by a number of external factors, such as nutritional supplements. In this study, the modulatory effect of four dietary supplements, maslinic acid (MA), hydroxytyrosol (HT), glycine, and aspartate (AA), on hepatic intermediary metabolism was observed in Wistar rats with induced tendinopathy at different stages of the disease. Induced tendinopathy in rats produces alterations in the liver intermediary metabolism. Nutraceutical treatments modify the intermediary metabolism in the different phases of tendinopathy, so AA treatment produced a decrease in carbohydrate metabolism. In lipid metabolism, MA and AA caused a decrease in lipogenesis at the tendinopathy and increased fatty acid oxidation. In protein metabolism, MA treatment increased GDH and AST activity; HT decreased ALT activity; and the AA treatment does not cause any alteration. Use of nutritional supplements of diet could help to regulate the intermediary metabolism in the TP.

The Achilles tendon is the thickest and strongest tendon of the human body, and it is frequently injured during sports activity. The incidence of Achilles tendon pathologies has increased over recent decades, especially in the last few years, because of increased sports participation among the general population and due to the diffusion of competitive sports at a high level. Tendinopathies are common in athletes and in middle-aged overweight patients. The term "tendinopathy" refers to a condition characterised clinically by pain and swelling, with functional limitations of tendon and nearby structures, and consequently to chronic failure of healing response process. Tendinopathies can produce marked morbidity, and at present, scientifically validated management modalities are limited. Despite the constantly increasing interest and number of studies about Achilles tendinopathy (AT), there is still not a consensual point of view on which is the best treatment, and its management is still controversial. AT can be treated conservatively primarily, with acceptable results and clinical outcomes. When this approach fails, surgery should be considered. Several surgical procedures have been described for both conditions with a relatively high rate of success with few complications and the decision for treatment in patients with AT should be tailored on patient's needs and level of activity. The aim of this article is to give insights about the pathogenesis and most used and recent treatment options for AT.

Background: The aim of this study is to evaluate the association between occupational exposure to biomechanical risk factors and shoulder tendinopathies., Methods: We updated recent systematic reviews about specific shoulder disorders and work-related risk factors. MEDLINE was searched up to September 2022. Studies satisfying the following criteria were included: i) the diagnosis was based on physical examination plus imaging data (when available), and ii) the exposure assessment was based on video analysis and/or directly measured., Results: Five studies met the inclusion criteria: three cross-sectional studies identified from published systematic reviews and two cohort studies retrieved from the update. Two studies investigated shoulder tendinitis, one supraspinatus tendinitis, and the other two rotator cuff syndrome. The diagnosis was based on physical examination, not supported by imaging techniques for all the included studies. In four out of five studies, the exposure was assessed by experienced ergonomists with the support of video recordings. In two studies, the exposure assessment was further supplemented by force gauge measurements or direct measurements of upper arm elevation. Only the combined exposure of working with arms above shoulder level with forceful hand exertion appears to be associated with rotator cuff syndrome: i) a cohort study reported an HR=1.11 (95%CI 1.01-1.22) for each unit increase in forceful repetition rate when the upper arm is flexed ≥45° for ≥29% of the working time; and ii) a cross-sectional study showed an OR=2.43 (95%CI 1.04-5.68) for the combination of upper arm flexion ≥45° for more than 15% of the time with a duty cycle of forceful exertions more than 9% of the time., Conclusions: There is moderate evidence of a causal association between shoulder tendinopathy and combined exposures of working above shoulder level with forceful hand exertion. The evidence is insufficient for any single biomechanical exposure on its own. High-quality cohort studies with direct exposure measures and objective diagnostic criteria are needed. The occupational origin of shoulder tendinopathies is still an open question that must be properly answered.

Competing Interests: The author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

Competing Interests: The author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

Background: Tendinopathy, enthesopathy, labral degeneration, and pathologic conditions of the articular disc (knee meniscus and ulnocarpal) are sometimes described in terms of inflammation or damage, while the histopathologic findings are often consistent with mucoid degeneration. A systematic review of the histopathology of these structures at diverse locations might reconceptualize these diseases as expected aspects of human aging. The potential benefits of this evolution might include healthier patient and clinician mindsets as well as a reduced likelihood of overdiagnosis and overtreatment resulting from greater awareness of base rates of pathology., Question/purpose: In this systematic review of studies of surgical specimens, we asked: Are there are any differences in the histopathologic findings of structural soft tissue conditions (mucoid degeneration, inflammation, and vascularity) by anatomic site (foot, elbow, or knee) or structure (tendon body, muscle or tendon origin or insertion [enthesis], labrum, or articular disc)?, Methods: Studies between 1980 and 2021 investigating the histopathologic findings of specimens from surgery for trigger digit, de Quervain tendinopathy, plantar fasciitis, lateral and medial elbow enthesopathy, rotator cuff tendinopathy, posterior tibial tendinopathy, patellar tendinopathy, Achilles tendinopathy, or disease of the hip labrum, ulnocarpal articular disc, or knee meniscus were searched for in the PubMed, EMBASE, and CINAHL databases. Inclusion criteria were the prespecified anatomic location or structure being analyzed histologically and any findings described with respect to inflammation, vascularity, or mucoid degeneration. Studies were excluded if they were nonhuman studies or review articles. Search terms included "anatomy," "pathology," and "histopathology." These terms were coupled with anatomic structures or disorders and included "trigger finger," "de Quervain," "fasciitis, plantar," "tennis elbow," "rotator cuff tendinopathy," "elbow tendinopathy," "patellar tendonitis," "posterior tibial tendon," and "triangular fibrocartilage." This resulted in 3196 studies. After applying the inclusion criteria, 559 articles were then assessed for eligibility according to our exclusion criteria, with 52 eventually included. We recorded whether the study identified the following histopathologic findings: inflammatory cells or molecular markers, greater than expected vascularity (categorized as quantitative count, with or without controls; molecular markers; or qualitative judgments), and features of mucoid degeneration (disorganized collagen, increased extracellular matrix, or chondroid metaplasia). In the absence of methods for systematically evaluating the pathophysiology of structural (collagenous) soft tissue structures and rating histopathologic study quality, all studies that interpreted histopathology results were included. The original authors' judgment regarding the presence or absence of inflammation, greater than expected vascularity, and elements of mucoid degeneration was recorded along with the type of data used to reach that conclusion., Results: Regarding differences in the histopathology of surgical specimens of structural soft tissue conditions by anatomic site, there were no differences in inflammation or mucoid degeneration, and the knee meniscus was less often described as having greater than normal vascularity. There were no differences by anatomic structure. Overall, 20% (10 of 51) of the studies that investigated for inflammation reported it (nine inflammatory cells and one inflammatory marker). Eighty-three percent (43 of 52) interpreted increased vascularity: 40% (17 of 43) using quantitative methods (14 with controls and three without) and 60% (26 of 43) using imprecise criteria. Additionally, 100% (all 52 studies) identified at least one element of mucoid degeneration: 69% (36 of 52) reported an increased extracellular matrix, 71% (37 of 52) reported disorganized collagen, and 33% (17 of 52) reported chondroid metaplasia., Conclusion: Our systematic review of the histopathology of diseases of soft tissue structures (enthesopathy, tendinopathy, and labral and articular disc) identified consistent mucoid degeneration, minimal inflammation, and imprecise assessment of relative vascularity; these findings were consistent across anatomic sites and structures, supporting a reconceptualization of these diseases as related to aging (senescence or degeneration) rather than injury or activity., Clinical Relevance: This reconceptualization supports accommodative mindsets known to be associated with greater comfort and capability. In addition, awareness of the notable base rates of structural soft tissue changes as people age might reduce overdiagnosis and overtreatment of incidental, benign, or inconsequential signal changes and pathophysiology., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2022 by the Association of Bone and Joint Surgeons.)

Objectives: Thymoquinone is a major bioactive compound present in the black seeds of the Nigella sativa. Tendon injuries are almost 50% of all musculoskeletal injuries. The recovery of tendon after surgery has become a significant challenge in orthopedics., Design: The purpose of this study was to investigate the healing effect of thymoquinone injections in 40 New Zealand rabbits tendon traumatic models., Materials and Methods: Tendinopathy was induced by trauma using surgical forceps on the Achilles tendon. Animals were randomly divided into 4 groups: (1) normal saline injection (control), (2) DMSO injection, (3) thymoquinone 5% w/w injection, and (4) thymoquinone 10% w/w injection. Forty-two days after surgery, biochemical and histopathological evaluations were done, and biomechanical evaluation was conducted 70 days after surgery., Results: Breakpoint and yield points in treatment groups were significantly higher compared to control and DMSO groups. Hydroxyproline content in the 10% thymoquinone receiving group was higher than all groups. Edema and hemorrhage in the histopathological evaluation were significantly lower in the thymoquinone 10% and thymoquinone 5% receiving groups compared to control and DMSO groups. Collagen fibers, collagen fibers with fibrocytes, and collagen fibers with fibroblasts were significantly higher in the thymoquinone 10% and thymoquinone 5% receiving groups compared to control groups., Conclusions: Thymoquinone injection in the tendon in the concentration of 10% w/w is a simple and low-cost healing agent that could enhance mechanical and collagen synthesis in traumatic tendinopathy models in rabbit., (© 2023. The Author(s).)

Background: The purpose of the present investigation was to evaluate the immediate effect of running a marathon on Achilles tendon anteroposterior thickness., Methods: In 25 runners who took part in the London marathon, ultrasonography was used to measure the Achilles tendon thickness pre- and immediately post-marathon and to identify any structural abnormalities indicating tendinopathy. Pain was recorded using a numerical rating scale at baseline and post-marathon. Twenty-one participants were included in the final analysis., Results: Running a marathon resulted in a significant decrease (- 13%, p < 0.01) in anteroposterior diameter of the Achilles tendon immediately following the marathon. There was no change in the proportion of Achilles tendons with structural abnormalities (34%) or pain (12%) following the marathon (p > 0.05)., Conclusion: Running a marathon resulted in an immediate reduction in anteroposterior diameter of the Achilles tendon. This finding may have implications for injury prevention and recovery following a marathon., (© 2022. The Author(s).)

Purpose: Dorsal closing wedge calcaneal osteotomy (DCWCO) is indicated in patients with insertional tendinopathy of the calcaneal (Achilles) tendon. The Chauveaus-Liet's (CL) angle is represented by the difference between the angle of verticalization (α) and morphological angle (β) of the calcaneus (CL angle = α - β). The purpose of the study was to assess whether the DCWCO affects the Chauveaus-Liet's angle., Methods: The study included 12 patients indicated to DCWCO. Three directions of close wedge osteotomy were designed for each patient-horizontal, vertical and in the middle type of osteotomy and a virtual osteotomy was created in each of them in the ABAQUS system in cooperation with Czech Technical University. The most used directions of osteotomy according to the available literature were used. We evaluated α and β angles before and after osteotomy, changes of the length plantar aponeurosis and the elevation of distal insertional point of the calcaneal tendon. The changes of grades, median and standard deviation were observed., Results: The change of the alfa angle was dependent on the direction of the osteotomy and the change of the beta angle was affected by the size of the osteotomy. The greatest elevation of the distal insertional point of the calcaneal tendon occurred in the horizontal type of the osteotomy., Conclusion: Our study shows that the more we want to reduce the tension in the calcaneal tendon, the more we have to perform an osteotomy horizontally. This study could serve as a preoperative guide for osteotomy planning., (© 2022. The Author(s).)

Objective: To establish and validate an intact rotator cuff rat model for exploring the pathophysiological effects of type 2 diabetes on the rotator cuff tendon in vivo ., Methods: A total of 45 adult male rats were randomly divided into a control group (n = 9) and type 2 diabetes group (n=36). The rats were sacrificed at 2 weeks (T2DM-2w group, n=9), 4 weeks (T2DM-4w group, n=9), 8 weeks (T2DM-8w group, n=9), and 12 weeks (T2DM-12w group, n=9) after successful modeling of type 2 diabetes. Bilateral shoulder samples were collected for gross observation and measurement, protein expression(enzyme-linked immunosorbent assay,ELISA), histological evaluation, biomechanical testing, and gene expression (real-time quantitative polymerase chain reaction, qRT-PCR)., Results: Protein expression showed that the expression of IL-6 and Advanced glycation end products (AGEs)in serum increased in type 2 diabetic group compared with the non-diabetic group. Histologically, collagen fibers in rotator cuff tendons of type 2 diabetic rats were disorganized, ruptured, and with scar hyperplasia, neovascularization, and extracellular matrix disturbances, while Bonar score showed significant and continuously aggravated tendinopathy over 12 weeks. The biomechanical evaluation showed that the ultimate load of rotator cuff tendons in type 2 diabetic rats gradually decreased, and the ultimate load was negatively correlated with AGEs content. Gene expression analysis showed increased expression of genes associated with matrix remodeling (COL-1A1), tendon development (TNC), and fatty infiltration (FABP4) in tendon specimens from the type 2 diabetic group., Conclusion: Persistent type 2 diabetes is associated with the rupture of collagen fiber structure, disturbance in the extracellular matrix, and biomechanical decline of the rotator cuff tendon. The establishment of this new rat model of rotator cuff tendinopathy provides a valuable research basis for studying the cellular and molecular mechanisms of diabetes-induced rotator cuff tendinopathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Zhang, Ren, Wang, Zhang, Zhao and Yu.)

Objective: To investigate the prevalence of rotator cuff and long head of the biceps pathologies in manual wheelchair (MWC) users with spinal cord injury (SCI). Design: Cross-sectional study. Setting: Outpatient clinic at a tertiary medical center. Participants: Forty-four adult MWC users with SCI (36 men and 8 women) with an average age (SD) of 42 (13) years. SCI levels ranged from C6 to L1; complete and incomplete SCI. Outcome Measures: Participants' demographic and anthropometric information, presence of shoulder pain, Wheelchair User's Pain Index (WUSPI) scores, and magnetic resonance imaging findings of shoulder pathologies including tendinopathy, tendon tears, and muscle atrophy. Results: Fifty-nine percent of the participants reported some shoulder pain. The prevalence of any tendinopathy across the rotator cuff and the long head of biceps tendon was 98%. The prevalence of tendinopathy in the supraspinatus was 86%, infraspinatus was 91%, subscapularis was 75%, and biceps was 57%. The majority of tendinopathies had mild or moderate severity. The prevalence of any tears was 68% . The prevalence of tendon tears in the supraspinatus was 48%, infraspinatus was 36%, subscapularis was 43%, and biceps was 12%. The majority of the tears were partial-thickness tears. Participants without tendon tears were significantly younger (P < 0.001) and had been wheelchair user for a significantly shorter time (P = 0.005) than those with tendon tears. Conclusion: Mild and moderate shoulder tendinopathy and partial-thickness tendon tears were highly prevalent in MWC users with SCI. Additionally, the findings of this study suggest that strategies for monitoring shoulder pathologies in this population should not be overly reliant on patient-reported pain, but perhaps more concerned with years of wheelchair use and age.

Achilles tendinopathy is a common overuse injury, especially among runners. It should be divided into midportion Achilles tendinopathy and insertional Achilles tendinopathy, as the treatments are different. Achilles tendinopathy is a clinical diagnosis, which includes a combination of pain, swelling and stiffness. If pain is located 2-6 cm above the insertion to the calcaneus, it is considered a midportion tendinopathy. Pain located more distally, close to the insertion, is defined as insertional tendinopathy. Both midportion and insertional Achilles tendinopathies are primarily treated with physiotherapy during three to six months. Exercise has the highest level of evidence and is more successful in midportion Achilles tendinopathy. Insertional tendinopathy more often requires surgical treatment, with removal of bony exostosis and chronically inflamed bursa.

Background: Treatment of degenerating tendons still presents a major challenge, since the aetiology of tendinopathies remains poorly understood. Besides mechanical overuse, further known predisposing factors include rheumatoid arthritis, diabetes, obesity or smoking all of which combine with a systemic inflammation., Methods: To determine whether the systemic inflammation accompanying these conditions contributes to the onset of tendinopathy, we studied the effect of a systemic inflammation induced by an allergic episode on tendon properties. To this end, we induced an allergic response in mice by exposing them to a timothy grass pollen allergen and subsequently analysed both their flexor and Achilles tendons. Additionally, we analysed data from a health survey comprising data from more than 10.000 persons for an association between the occurrence of an allergy and tendinopathy., Findings: Biomechanical testing and histological analysis revealed that tendons from allergic mice not only showed a significant reduction of both elastic modulus and tensile stress, but also alterations of the tendon matrix. Moreover, treatment of 3D tendon-like constructs with sera from allergic mice resulted in a matrix-remodelling expression profile and the expression of macrophage-associated markers and matrix metalloproteinase 2 (MMP2) was increased in allergic Achilles tendons. Data from the human health study revealed that persons suffering from an allergy have an increased propensity to develop a tendinopathy., Interpretation: Our study demonstrates that the presence of a systemic inflammation accompanying an allergic condition negatively impacts on tendon structure and function., Funding: This study was financially supported by the Fund for the Advancement of Scientific Research at Paracelsus Medical University (PMU-FFF E-15/22/115-LEK), by the Land Salzburg, the Salzburger Landeskliniken (SALK, the Health Care Provider of the University Hospitals Landeskrankenhaus and Christian Doppler Klinik), the Paracelsus Medical University, Salzburg and by unrestricted grants from Bayer, AstraZeneca, Sanofi-Aventis, Boehringer-Ingelheim., Competing Interests: Declaration of interest ET declares his interests as follows: Grants or contracts from any entity: Austrian Science Fund (FWF), Österreichische Nationalbank, European Union, GSK, Biogen, Eisai, Noartis, Red Bull, Bayer, UCB Consulting fees: UCB, Eisai, Bial, Medtronic, Everpharma, GSK, Liva-Nova, Newbridge, Novartis, Sanofi, Sandoz, Biogen, Takeda, Sunovion, GW Pharm, Marinus, Arvelle, Argenix, Epilog, Clexio Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: UCB, Eisai, Biogen, Novartis, Bial, Sunovion, Ever-Pharma, Liva-Nova, Sanofi, Hikma, Newbridge, Arvell, GW-Pharm, Sandoz Participation on a Data Safety Monitoring Board or Advisory Board: Marinus UCB, (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Tendinopathy is common, presents with pain and activity limitation, and is associated with a high risk of recurrence of the injury. Tendinopathy usually occurs as a results of a disrupted healing response to a primary injury where cellular and molecular pathways lead to low grade chronic inflammation., Main Findings: There has been a renewed interest in investigating the role of Inflammation in the pathogenesis of tendinopathy, in particular during the initial phases of the condition where it may not be clinically evident. Understanding the early and late stages of tendon injury pathogenesis would help develop new and effective treatments addressed at targeting the inflammatory pathways., Conclusion: This review outlines the role of low-grade Inflammation in the pathogenesis of tendinopathy, stressing the role of proinflammatory cytokines, proteolytic enzymes and growth factors, and explores how Inflammation exerts a negative influence on the process of tendon healing., (© 2021. The Author(s).)

Background: The aetiopathogenesis of tendinopathy is uncertain, but inflammation may play a role in the early phase of tendinopathy and in tendon healing response. We investigated the most up-to-date evidence about the association between obesity, high-fat diet and tendinopathy, focusing on the role of adipokines, inflammatory pathways and molecular changes., Sources of Data: A systematic review was performed searching PubMed, Embase and Cochrane Library databases following the PRISMA guidelines. We included studies of any level of evidence published in peer-reviewed journals. The risk of bias (SIRCLE) was assessed, as was the methodological quality (CAMARADES) of the included studies. We excluded all the articles with a high risk of bias and/or low quality after the assessment. After applying the inclusion and exclusion criteria, we included 14 studies of medium or high quality., Areas of Agreement: A high-fat diet negatively affects tendon quality, increasing the risk of rupture and tendinopathy., Areas of Controversy: Controversial evidence exists on both tendon fat infiltration secondary to a dysregulation of the lipid metabolism and of a molecular effect of inflammatory pathways., Growing Points: The secretion of adipokines is strictly related to fat ingestion and body composition and can potentially act on tendon physiology and injury., Areas Timely for Developing Research: Adipokines, low-grade inflammation and fat intake play a role in disrupting tendon healing and setting up tendinopathy. Further high-quality research is needed to better define the molecular pathways involved., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Abstract: Achilles tendinopathy is a common overuse condition that is characterized by degenerative, cumulative tissue microtrauma. It is largely a clinical diagnosis in which the patient typically presents with localized pain that is worse with tendon-loading activities. Imaging modalities may be helpful with the diagnosis of difficult cases or in the planning of interventional procedures. Midportion (noninsertional) and insertional tendinopathy have distinct features and differences for therapeutic paradigms. Overall, Achilles tendinopathy has a good clinical prognosis with most patients improving with activity modification and rehabilitation, with a focus on progressive tendon-loading. Recalcitrant cases may require adjuvant treatment with procedures (e.g., injections, shockwave therapy) and rarely surgical intervention., (Copyright © 2021 by the American College of Sports Medicine.)

Objectives: The Achilles tendon, which is composed of tendinous parts of gastrocnemius and soleus muscles, is the strongest and the largest tendon in the human body. Chronic renal disease can lead to reduced physical activity and exercise capacity. Spontaneous rupture of the Achilles tendon can occur in patients with chronic renal failure, with recurrent microtraumas, hypoxia, and chronic acidosis as predisposing factors. Here, we assessed and compared the elastographic findings in the Achilles tendon using acoustic radiation force impulse elastography in patients on chronic hemodialysis, in renal transplant patients, and in healthy volunteers., Materials and Methods: Our study included 25 patients on chronic hemodialysis, 25 renal transplant patients, and 25 healthy individuals (control group). The thickness and shear wave velocity of the Achilles tendons were measured bilaterally by ultrasonography and acoustic radiation force impulse elastography., Results: The mean shear wave velocity was 3.67 m/s in the right and 3.64 m/s in the left Achilles tendon in the hemodialysis group. In the renal transplant group, the mean shear wave velocity was 4.29 and 4.25 m/s for the right and left Achilles tendon, respectively. In the control group, the mean shear wave velocity was 6.68 and 6.59 m/s, respectively for the right and left Achilles tendon. A statistically significant difference in shear wave velocities was shown among the groups (P < .05)., Conclusions: Achilles tendons in patients with chronic renal failure and on hemodialysis were softer than in renal transplant patients and softer than in the control group. Chronic tendinopathy causes softening of the tendon. In the renal transplant group, stiffness of the Achilles tendon was increased versus the hemodialysis group but still softer than the control group, which could be explained as a positive clinical effect of renal transplant. Acoustic radiation force impulse elastography is an objective, easy, and noninvasive method to assess Achilles tendinopathy.

To examine the differential mechanobiological responses of specific resident tendon cells, we developed an in vivo model of whole-body irradiation followed by injection of either tendon stem/progenitor cells (TSCs) expressing green fluorescent protein (GFP-TSCs) or mature tenocytes expressing GFP (GFP-TNCs) into the patellar tendons of wild type C57 mice. Injected mice were subjected to short term (3 weeks) treadmill running, specifically moderate treadmill running (MTR) and intensive treadmill running (ITR). In MTR mice, both GFP-TSC and GFP-TNC injected tendons maintained normal cell morphology with elevated expression of tendon related markers collagen I and tenomodulin. In ITR mice injected with GFP-TNCs, cells also maintained an elongated shape similar to the shape found in normal/untreated control mice, as well as elevated expression of tendon related markers. However, ITR mice injected with GFP-TSCs showed abnormal changes, such as cell morphology transitioning to a round shape, elevated chondrogenic differentiation, and increased gene expression of non-tenocyte related genes LPL, Runx-2, and SOX-9. Increased gene expression data was supported by immunostaining showing elevated expression of SOX-9, Runx-2, and PPARγ. This study provides evidence that while MTR maintains tendon homeostasis by promoting the differentiation of TSCs into TNCs, ITR causes the onset of tendinopathy development by inducing non-tenocyte differentiation of TSCs, which may eventually lead to the formation of non-tendinous tissues in tendon tissue after long term mechanical overloading conditions on the tendon., Competing Interests: The authors have declared that no competing interests exist.

Calcific tendinitis (CT) of the shoulder is a painful disorder usually identified in individuals aged 40 and 60 years. The estimated global prevalence of CT is 2.7% to 36%. We examined the association of hyperlipidemia and sex with CT of the shoulder using Taiwan Biobank (TWB) and the National Health Insurance Research Database (NHIRD).Data were available for 9903 TWB participants who were recruited between 2008 and 2015. We used multiple logistic regression analysis to estimate the odds ratios (OR) and 95% confidence intervals (CI) for CT of the shoulder.Overall, 1564 women, and 1491 men were identified with hyperlipidemia. Women, compared to men, had higher odds of CT of the shoulder (OR, 1.53; 95% CI, 1.08-2.16). Hyperlipidemia, compared to no hyperlipidemia, was associated with an increased risk of CT (OR, 1.40; 95% CI, 1.02-1.93). The test for interaction was significant for sex and hyperlipidemia (P = .006). After stratification, the odds ratio for CT was 1.95 (95% CI, 1.30-2.92) in women and 0.82 (95% CI, 0.48-1.39) in men, respectively. Compared to men with no hyperlipidemia, the odds ratio was 0.86 (95% CI, 0.53-1.38) for men with hyperlipidemia and 2.00 (95% CI, 1.29-3.10) for women with hyperlipidemia.Importantly, our findings indicated that the risk for CT of the shoulder was higher among Taiwanese women with hyperlipidemia. However, CT risk among their male counterparts with hyperlipidemia was not significant.

Background: Gout has been associated with weaker foot/leg muscles and altered gait patterns. There is also evidence of on-going foot pain and an increased risk of tendinopathy, with the Achilles and patella tendons most frequently affected in gout. Additionally, the inflammation associated with gout may change tissue elasticity. Ultrasound imaging utilising shear wave elastography (SWE) offers a non-invasive method of quantifying changes in tendon stiffness. SWE findings have not previously been reported in individuals with gout. We sought to determine differences in Achilles tendon stiffness in people with gout compared to controls (non-gout)., Methods: A cross sectional study comparing 24 people with gout and 26 age/sex-matched controls. Clinical and demographic data were collated, and US imaging used to determine tendon thickness, presence of gouty tophi and/or aggregates and levels of angiogenesis. Ten shear wave elastography (SWE) measures were taken along the centre of a longitudinal section of the mid-portion of each Achilles tendon. Prior to data collection, intra-observer error was good (>0.69). Data were summarised using descriptive statistics and a repeated measures ANCOVA was used to compare SWE measures between the two groups for the left and right foot separately after accounting for Body Mass Index (BMI)., Results: A small proportion of those with gout presented with intra-tendon aggregates and/or intra-tendon tophi in one or both tendons. There was no statistically significant difference in tendon thickness between groups. Neo-vascularity was present in a third of gout participants. SWE findings demonstrated significantly reduced tendon stiffness in those with gout compared to controls: right Achilles mdiff =1.04 m/s (95% CI (0.38 to 1.7) p = 0.003 and left Achilles mdiff = 0.7 m/s (95% CI 0.09 to 1.32) p = 0.025. No relationship between the presence of tophi and SWE values were detected., Conclusion: Subjects with chronic gout show significantly reduced Achilles tendon stiffness compared to non-gout controls. From a clinical standpoint, our findings were similar to SWE measurements in subjects with Achilles tendinopathy and who did not have gout.

Calcific tendinopathy is a condition that is related to the deposition of calcium, mostly hydroxyapatite crystals, within the tendons. The shoulder and the hip are commonly affected joints, but calcific tendinopathy may occur in any tendon of the body. While there is an extensive literature on the ultrasound diagnosis of calcific tendinopathy of the shoulder, there are only sporadic reports on other sites. This review combines the experience of our centers and a thorough analysis of the literature from the last 45 years (1972-2017) in order to highlight the localizations beyond the rotator cuff, their ultrasound characteristics and therapeutic possibilities.

Femoroacetabular impingement (FAI) is the most common cause of hip pain in both professional and recreational athletes. It is caused by abnormal bone development on both the acetabulum and proximal femur as a result of genetic factors and in reaction to high-volume athletics participation. Athletes typically become symptomatic after reaching skeletal maturity and commonly describe deep groin pain that worsens with activities such as squatting, cutting, or pivoting motions. For this reason, sports such as hockey, football, and soccer can be particularly irritating to an athlete with FAI. Moreover, the athlete with FAI often presents with contaminant hip and pelvis pathologies such as athletic pubalgia and iliopsoas tendinopathy that must also be addressed. While this pain often limits performance or participation in sports, perhaps the most significant ramification of FAI is the role it plays in driving early onset osteoarthritis. Fortunately, FAI can be reliably diagnosed through careful history taking, appropriate provocative physical exam maneuvers, and familiarity with hallmark radiographic features. The aims of this review are to provide clinicians with information regarding the pathogenesis of FAI, to thoroughly describe the classic history and physical exam elements, and to introduce various management strategies for athletes suffering from FAI.

Groin pain can be caused by a myriad of pathologies. Abnormalities of the rectus femoris are a very rare cause of groin pain; calcific tendinopathy of the direct head is particularly so, with only two case reports in the literature. We report the first case of calcific tendinopathy of the direct head of the rectus femoris that was treated effectively with ultrasound-guided percutaneous irrigation of calcific tendinopathy (USPICT). The anatomy of the rectus femoris and the technique for US-PICT of the rectus femoris are also described.

Background: Inflammation and mechanical demands play a role in the development of tendon conditions and the dysregulation of tendon healing. In patients with obesity, high levels of pro-inflammatory cytokines and a high mechanical demand promote chronic low-grade inflammation. Although controversial results have been reported, we aimed to summarize current evidence while highlighting the role of obesity in tendinopathy., Questions/purposes: (1) Do patients with obesity have a greater risk of tendinopathy, stratified by upper and lower extremity sites, than patients who do not have obesity? (2) Is obesity associated with a higher risk of upper and lower extremity tendon tear and ruptures? (3) Is obesity associated with an increased risk of complications after upper and lower extremity tendon surgery?, Methods: We performed a systematic review by searching the PubMed, Embase, and Cochrane Library databases, combining the term "tendon" with common terms for tendinopathy and rupture such as "tendon injury OR tendinopathy OR tendon rupture" and "obese" OR "obesity." We included studies with any level of evidence published from January 2000 to July 10, 2019 in peer-reviewed journals reporting clinical results. After we removed the duplicates, there were 365 records. Two independent authors screened these records and excluded 320 based on abstract and title screening. Of the remaining 45 studies, 23 were excluded because the topic did not address the research questions (n = 19), the article was outdated (n = 3), or because there was a serious risk of bias (n = 1). Finally, we included 22 studies with 49,914 participants (5984 with obesity), 31,100 (1884 with obesity) of whom had upper-extremity tendinopathy, while 18,814 (4010 with obesity) had lower-extremity tendinopathy. Obesity was defined as a BMI ≥ 30 kg/m according to the WHO's criteria. Data were extracted and analyzed critically. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied, and the risk of bias (ROBINS tool) of the studies was assessed, as was the methodological quality (Coleman score). The assessment was performed independently by two authors. Inter-rater agreement for the assessments of the risk of bias and methodological quality were 89% and 94%, respectively. All studies were observational, and most were retrospective case-control studies. Any discrepancy was discussed and solved by consensus. The articles had a moderate risk of bias (eight articles) or a low risk of bias (fourteen articles). We excluded one article because of a serious risk of bias. The mean (range) Coleman score was 53.5 (42-74)., Results: Obesity was associated with a greater risk of upper extremity tendinopathy (rotator cuff: odds ratio 1.25 [95% confidence interval 1.12 to 1.40]; p < 0.001; medial epicondylitis: OR 1.9 [95% CI 1.0 to 3.7]; p < 0.05) and lower-extremity tendinopathy (Achilles tendon: OR 3.81 [95% CI 2.57 to 5.63]; OR 3.77 [95% CI 2.24 to 6.34]; OR 6.56 [95% CI 3.18 to 13.55], for obesity Classes I, II and III, respectively; patellar tendon: OR 1.10 [95% CI 1.05 to 1.90]; p = 0.001; plantar fascia: OR 2.97 [95% CI 1.64 to 5.37]; p = 0.004). Obesity was associated with a greater risk of upper extremity tendon tear (rotator cuff: OR 2.35 [95% CI 1.62 to 3.40]; p < 0.001) and rupture leading to tendon surgery (rotator cuff in men: OR 3.13 [95% CI 1.29 to 7.61]; p < 0.001 and women: OR 3.51 [95% CI 1.80 to 6.85]; p < 0.001). However, no association was found between BMI and lower extremity rupture (Achilles mean BMI: 27.77 kg/m [95% CI 26.94 to 28.49] versus control: 26.66 kg/m [95% CI 26.06 to 27.27]; p = 0.047). Upper extremity complications (n = 359) after tendon repair surgery had a weighted incidence of 13.27% and 8.13% for rotator cuff surgery in patients with and without obesity, respectively. In the lower extremity (n = 21,152), the weighted incidence for Achilles tendon surgery was 11.28% and 8.6% in patients with and without obesity, respectively., Conclusions: Obesity is associated with a higher risk of tendinopathy, tendon tear and rupture, and complications after tendon surgery than non-obesity. However, the high heterogeneity and observational nature of the studies highlight the need to be cautious about the results of our study. We encourage researchers to perform clinical and preclinical studies to explore pathways related to the metabolic state of this population., Level of Evidence: Level IV, prognostic study.

Context: After knee-joint injury, pain, effusion, and mechanoreceptor damage alter afferent signaling, which can result in quadriceps inhibition and subsequent weakness. The individual contributions of each factor to inhibition remain unclear due to confounding knee-joint injuries and indirect experimental models., Objective: To characterize the influence of naturally occurring knee damage and pain on quadriceps neuromuscular function in individuals with patellar tendinopathy., Design: Cross-sectional study., Setting: Research laboratory., Patients or Other Participants: Twenty participants who self-reported patellar tendinopathy (PT) and 10 healthy control individuals underwent ultrasonic tendon assessment. Injured participants were dichotomized by an orthopaedic surgeon into groups with (1) pain and structural tendon abnormality and (2) regional pain alone., Main Outcome Measure(s): Quadriceps inhibition was assessed with the Hoffman reflex and the central activation ratio via the superimposed-burst technique. Normally distributed measures were analyzed using a 1-way analysis of variance and post hoc independent t tests. Kruskal-Wallis tests with post hoc Mann-Whitney U tests were used to analyze nonnormally distributed data. An a priori α level of P ≤ .05 was set., Results: Control participants presented with more spinal-reflex excitability (0.37 ± 0.23) than the PT (0.10 ± 0.06; P = .03) and regional-pain (0.18 ± 0.05; P = .02) groups. Knee-extension strength was greater in the control (3.37 ± 0.59 Nm/kg) than in the PT (2.41 ± 0.67 Nm/kg; P = .01) group but not the regional-pain group (3.05 ± 0.66 Nm/kg; P = .24). Control individuals presented with more quadriceps activation (97.93% ± 3.12) than the PT (84.44% ± 16.98; P < .01) and regional-pain (91.17% ± 10.56; P = .01) groups. No differences were present for any measures between the PT and regional-pain groups (P values > .05)., Conclusions: Deficits in spinal-reflex excitability, quadriceps activation, and strength were present in both the PT and regional-pain groups. A combination of pain and structural damage appeared to have the greatest negative effect on quadriceps function, as only the PT group presented with neuromuscular outcomes that failed to meet clinical thresholds., (© by the National Athletic Trainers' Association, Inc.)

Background: Achilles sleeve avulsion usually occurs from pre-existing insertional Achilles tendinopathy, leaving a calcific spur at the insertional site. The purpose of this study was to introduce a new technique using the spur base on the insertional site to drill the suture tunnel to repair Achilles sleeve avulsion., Methods: In total, 11 patients diagnosed with Achilles sleeve avulsion underwent this new surgical technique and were followed for a mean time of 40 months. Clinical outcomes were measured using the visual analog scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) score, Victorian Institute of Sports Assessment-Achilles (VISA-A) score, Tegner score, and time taken to return to activities. Preoperative and postoperative MRI, the ability to perform heel rise, and complications were also evaluated., Results: All cases (11/11) had insertional Achilles tendinopathy with calcific spur formation on the tendon's insertion. At final follow-up, the average VAS score improved from 5.3 to 0.1, AOFAS score improved from 44.8 to 97.9, VISA-A score improved from 23.6 to 96.6, and Tegner score improved from 0.9 to 4.9. Tendinopathy symptoms were eliminated. Patients returned to daily activities, work, and sports 3.5 months, 2.8 months, and 12.3months after operation, respectively. Patients took an average of 18.1 weeks after operation to perform the single heel rise test. No severe complications such as infection and rerupture were observed., Conclusion: Our new transosseous suture technique is a promising alternative option in treating Achilles sleeve avulsion. More cases and longer follow up are needed in order to find the best reconstructive option for this pathology., Levels of Evidence: Level IV.

Background and Aim of the Work: The long head of biceps (LHB) is one of the tendons of the rotator cuff that runs strictly close to the humeral head. In case of pathology, it can be responsible for pain and shoulder impairment: in such cases, surgical options include tenotomy or tenodesis. The management of LHB along with surgery of the rotator cuff or during shoulder prosthetic replacement has been widely discussed in the literature. Conversely, the possibility of acute impingement and incarceration of LHB in proximal humerus fractures, as well as its role in shoulder pain in outcomes of these fractures, has been poorly considered., Methods: The following aspects in the literature on LHB and proximal humerus fractures have been analysed: its management during fixation of fractures, the possibility of interference of the tendon with reduction of fractures or dislocations of the shoulder and its possible role in chronic pain after fixation of proximal humerus fractures., Results: LHB can be an obstacle in the reduction of fractures, dislocations and fracture-dislocations. Only a few papers take into account acute surgery to LHB (tenotomy or tenodesis); most of the studies on fixation of proximal humerus fractures simply ignore the problem of LHB. The tendon can be a source of pain and a cause of disability in sequelae of these fractures., Conclusions: LHB should be taken into consideration both in the acute phase of fractures of the proximal humerus and in the outcomes. Other studies are needed to better understand its optimal management during fracture surgery.

Introduction: The role of the immune system in tendon healing relies on polymorphonucleocytes, mast cells, macrophages and lymphocytes, the 'immune cells' and their cytokine production. This systematic review reports how the immune system affects tendon healing., Sources of Data: We registered our protocol (registration number: CRD42019141838). After searching PubMed, Embase and Cochrane Library databases, we included studies of any level of evidence published in peer-reviewed journals reporting clinical or preclinical results. The PRISMA guidelines were applied, and risk of bias and the methodological quality of the included studies were assessed. We excluded all the articles with high risk of bias and/or low quality after the assessment. We included 62 articles assessed as medium or high quality., Areas of Agreement: Macrophages are major actors in the promotion of proper wound healing as well as the resolution of inflammation in response to pathogenic challenge or tissue damage. The immune cells secrete cytokines involving both pro-inflammatory and anti-inflammatory factors which could affect both healing and macrophage polarization., Areas of Controversy: The role of lymphocytes, mast cells and polymorphonucleocytes is still inconclusive., Growing Points: The immune system is a major actor in the complex mechanism behind the healing response occurring in tendons after an injury. A dysregulation of the immune response can ultimately lead to a failed healing response., Areas Timely for Developing Research: Further studies are needed to shed light on therapeutic targets to improve tendon healing and in managing new way to balance immune response., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The inhibition of the aberrant differentiation of tendon-derived stem cells (TDSCs) is a major target for the regeneration of damaged tendon tissues, as tendinopathy can be caused by the aberrant differentiation of TDSCs. We investigated whether the possible aberrant differentiation of TDSCs can be prevented by using adequate inhibitors. TDSCs extracted from chemically induced tendinopathy and injury-with-overuse tendinopathy models were cultured with 18α-glycyrrhetinic acid (AGA) and T0070907 to block osteogenic differentiation and adipogenic differentiation, respectively. The optimal dose of AGA decreased the osteogenic-specific marker Runx2 (Runt-related transcription factor 2), and T0070907 blocked the adipogenic-specific marker peroxisome proliferator-activated receptor gamma (PPARγ) in mRNA levels. We also found that AGA induced tenogenic differentiation in mRNA levels. However, T0070907 did not affect the tenogenic differentiation and regenerative capacity of TDSCs. We expect that optimal doses of AGA and T0070907 can prevent tendinopathy by inhibiting osteogenic and adipogenic differentiation, respectively. In addition, AGA and T0070907 may play important roles in the treatment of tendinopathy.

Rationale: With the development of ankle arthroscope techniques and procedures, the number of arthroscopic modified Broström procedures (MBPs) is increasing. All-inside arthroscopic MBP was developed recently, with good to excellent results. However, several complications have been reported in patients after arthroscopic MBP. This case report describes a rare complication of arthroscopic MBP., Patient Concerns: A 34-year-old woman presented with severe pain in her right ankle and underwent arthroscopic MBP for lateral ankle instability. About 6 months postoperatively, she presented with severe pain on the lateral aspect of the right ankle, especially while walking., Diagnosis: In physical examinations, there was marked swelling around the ankle and focal tenderness in the posterolateral malleolar area. Ankle ultrasonography showed a diffuse low-echoic mass-like lesion at the distal fibula between the fibular tip and peroneus tendon. T1-weighted sagittal magnetic resonance imaging images showed an irregularly shaped mass-like lesion with a heterogeneous signal near the distal fibula posteriorly where the anchor protruded., Interventions: The suture anchor in the posterior distal fibula area, which had irritated the peroneus tendon, was removed with debridement of the granulomatous lesion., Outcomes: At the 3-month follow-up, the patient was almost asymptomatic and had a nearly full range of motion. No complications or recurrent symptoms were noted at the 1-year follow-up., Lessons: Three-dimensional computed tomography studies of the appropriate fibular depth and position of suture anchors are needed to standardize the procedure and reduce complications.

Rationale: Deposition of tophus is a common feature in chronic gout; however, signs and symptoms are not always well-pronounced in cases of uncommon sites. We report a rare case with a tophaceous tendonitis on the flexor hallucis longus (FHL) tendon with tarsal tunnel syndrome (TTS). This is the first surgical case of TTS by gouty tophi in FHL., Patient Concerns: A 55-year-old woman presented with a 6-month history of mild discomfort at the right foot, which gradually worsened in the past 3 weeks. The patient visited our outpatient clinic due to persistent and aggravating foot pain and swelling around the tarsal tunnel., Diagnosis: The patient was diagnosed with hyperuricemia and diabetes mellitus with chronic kidney disease, and did not receive regular antigout treatments. Paresthesia was found along the distribution of medial and plantar nerve and tinel test was positive on tarsal tunnel. Biochemical examination showed she had raised serum uric acid (10.6 mg/dL) and decreased estimated glomerular filtration rate (69 mL/min/1.73 m). Conventional radiography examination showed negative pathology except soft tissue swelling. Magnetic resonance imaging revealed a fusiform mass within the FHL tendon and fluid collection around tarsal tunnel., Interventions: Surgical exploration was performed to remove the mass. Inflammation fluid exploded out from FHL tendon sheath, which was later proven to have infiltration of monosodium urate crystal. Superficial dissection revealed a white chalky mass and posterior tibial nerve was significantly compressed by the tophus mass., Outcomes: The mass was removed and the symptoms were relieved at immediate postoperative period., Lessons: A tophaceous tendonitis on FHL tendon can cause TTS and surgical decompression of the gout lesion can reduce the symptoms.

Patellar tendinopathy, or Jumper's knee, is a painful knee condition caused by inflammation of the patella tendon. This condition is most frequently observed in subjects who play sports that require repetitive regular jumping. Jumper's knee is frequently misdiagnosed as a minor injury and many athletes, like our patient, keep on training and competing and either tend to ignore the injury or attempt to treat it themselves. However, jumper's knee is a serious condition that requires a correct and timely diagnosis, which often necessitates ultrasound investigation in order to start the most appropriate treatment.

Background: Subacromial impingement syndrome is a common problem in primary healthcare. It often include tendinopathy. While exercise therapy is effective for this condition, it is not clear which type of exercise is the most effective. Eccentric exercises has proven effective for treating similar tendinopathies in the lower extremities. The aim of this systematic review was therefore to investigate the effects of eccentric exercise on pain and function in patients with subacromial impingement syndrome compared with other exercise regimens or interventions. A secondary aim was to describe the included components of the various eccentric exercise regimens that have been studied., Methods: Systematic searches of PubMed, Cochrane Library and PEDro by two independent authors. Included studies were assessed using the PEDro scale for quality and the Cochrane scale for clinical relevance by two independent authors. Data were combined in meta-analyses. GRADE was applied to assess the certainty of evidence., Results: Sixty-eight records were identified. Seven studies (eight articles) were included, six were meta-analysed (n = 281). Included studies were of moderate quality (median PEDro score 7, range 5-8). Post-treatment pain was significantly lower after eccentric exercise compared with other exercise: MD -12.3 (95% CI - 17.8 to - 6.8, I 2  = 7%, p < 0.001), but this difference was not clinically important. Eccentric exercise provided no significant post-treatment improvement in function compared with other exercise: SMD -0.10 (95% CI - 0.79 to 0.58, I 2  = 85%, p = 0.76). Painful eccentric exercise showed no significant difference compared to pain-free eccentric exercise. Eccentric training regimes showed both similarities and diversity. Intervention duration of 6-8 weeks was almost as effective as 12 weeks., Conclusions: Evidence of low certainty suggests that eccentric exercise may provide a small but likely not clinically important reduction in pain compared with other types of exercise in patients with subacromial impingement syndrome. It is uncertain whether eccentric exercise improves function more than other types of exercise (very low certainty of evidence). Methodological limitations of existing studies make these findings susceptible to change in the future., Trial Registration: PROSPERO CRD42019126917 , date of registration: 29-03-2019.

Background: Anterior overhang of the acetabular component is associated with iliopsoas impingement, which may cause groin pain and functional limitations after THA. However, little is known about the relationship between component overhang and functional alignment of the acetabular component. CT-based image simulation may be illuminating in learning more about this because CT images are more effective than radiographs for evaluating the component's overhang and position., Questions/purposes: Using CT simulations based on preoperative data of nondysplastic and dysplastic hips, we asked: (1) What are the differences in the amount of component overhang, defined as the mediolateral distance from the component's edge to the native acetabular bony boundary on axial images (axial overhang), and as the AP distance on sagittal images (sagittal overhang) among pelvises with neutral and posterior tilt (in which the cephalad portion of the pelvis is more posterior than the caudad portion in the sagittal plane) in patients with dysplastic hips and those with nondysplastic hips? (2) Are increments in the amount of component overhang associated with a difference in the likelihood that the iliopsoas tendon will impinge against the edge of the acetabular component, after controlling for native acetabular abduction and anteversion and the presence of dysplasia?, Methods: A total of 128 hips (dysplastic group: 73 hips; nondysplastic group: 55 hips) were evaluated. We defined a dysplastic hip as one with a lateral center-edge angle of less than 20° on AP radiographs. Pelvic models with neutral (0°) and 10° and 20° of posterior tilt were created from CT data. In simulations, acetabular component models were implanted into the true acetabulum with a tilt-adjusted orientation angle that was defined as the component's angle based on a reference for the functional pelvic plane (coronal plane of the body) in each pelvic model. Axial and sagittal component overhang were measured on CT images. Axial overhang of at least 12 mm and sagittal overhang of at least 4 mm were defined as thresholds increasing the likelihood of iliopsoas impingement according to previous studies. When determining the amount of overhang of the acetabular component, we controlled for abduction and anteversion of the native acetabulum and the presence of dysplasia by performing a multivariable logistic regression analysis., Results: In dysplastic hips, axial overhang increased by a mean ± SD of 5 ± 1 mm (Bonferroni adjusted p < 0.001; 95% CI, 4.7-5.1) from 0° to 10° of posterior tilt and by 5 ± 1 mm (p < 0.001; 95% CI, 4.9-5.3) from 10° to 20° of posterior tilt. Sagittal overhang increased by 1 ± 0 mm (p < 0.001; 95% CI, 1.0-1.0) from 0° to 10° of posterior tilt and by 1 ± 0 mm (p < 0.001; 95% CI, 1.0-1.0) from 10° to 20° of posterior tilt. In nondysplastic hips, axial overhang increased by a mean of 5 ± 0 mm (p < 0.001; 95% CI, 4.7-5.0) from 0° to 10° of posterior tilt and by 5 ± 1 mm (p < 0.001; 95% CI, 4.6-5.0) from 10° to 20° of posterior tilt. Sagittal overhang increased by 1 ± 0 mm (p < 0.001; 95% CI, 1.0-1.1) from 0° to 10° of posterior tilt and by 1 ± 0 mm (p < 0.001; 95% CI, 1.0-1.1) from 10° to 20° of posterior tilt. After controlling for the presence of dysplasia, we found that native acetabular abduction and anteversion and posterior pelvic tilt, presence of dysplasia (p = 0.030; adjusted odds ratio [OR], 2.2; 95% CI, 1.1-4.6), native acetabular anteversion (p < 0.001; adjusted OR, 1.4; 95% CI, 1.3-1.5), and 10° and 20° of backward tilt compared with 0° of tilt (10° of posterior tilt: p < 0.001; adjusted OR, 15; 95% CI, 5.5-41; 20° of posterior tilt: p < 0.001; adjusted OR, 333; 95% CI, 96-1157) were independently associated with axial overhang of at least 12 mm; the model showed high goodness of fit (Nagelkerke's r = 0.68). In contrast, native acetabular anteversion (p < 0.001; adjusted OR, 1.2; 95% CI, 1.1-1.2) and 20° of backward tilt compared with 0° of tilt (p = 0.015; adjusted OR, 2.2; 95% CI, 1.2-4.0) were independently associated with sagittal overhang of at least 4 mm; the model had low goodness of fit (Nagelkerke's r = 0.20)., Conclusions: Acetabular component overhang is more severe when the pelvis tilts posteriorly. Moreover, posterior pelvic tilt, the presence of dysplasia, and higher native acetabular anteversion were independently associated with an increased risk of component overhang. When 20° of posterior tilt was adjusted, the risk of severe overhang was especially increased., Clinical Relevance: Based on these results, surgeons can attempt to prevent severe overhang in patients with posterior pelvic tilt by increasing component anteversion and abduction; when component anteversion is increased by 8° and abduction is increased by 2° from the target angle of 15° of anteversion and 40° of abduction in patients with posterior tilt of 20°, the risk of severe overhang is reduced to by approximately one-twentieth. However, it is still unclear how much the degree of component anteversion should be increased when surgeons attempt to prevent anterior prosthetic dislocation at the same time. Future studies such as prospective clinical trials evaluating both prosthetic dislocation and iliopsoas impingement in patients with posterior tilt might clarify this issue.

Mechanical overloading is a major cause of tendinopathy, but the underlying pathogenesis of tendinopathy is unclear. Here we report that high mobility group box1 (HMGB1) is released to the tendon extracellular matrix and initiates an inflammatory cascade in response to mechanical overloading in a mouse model. Moreover, administration of glycyrrhizin (GL), a naturally occurring triterpene and a specific inhibitor of HMGB1, inhibits the tendon's inflammatory reactions. Also, while prolonged mechanical overloading in the form of long-term intensive treadmill running induces Achilles tendinopathy in mice, administration of GL completely blocks the tendinopathy development. Additionally, mechanical overloading of tendon cells in vitro induces HMGB1 release to the extracellular milieu, thereby eliciting inflammatory and catabolic responses as marked by increased production of prostaglandin E2 (PGE2) and matrix metalloproteinase-3 (MMP-3) in tendon cells. Application of GL abolishes the cellular inflammatory/catabolic responses. Collectively, these findings point to HMGB1 as a key molecule that is responsible for the induction of tendinopathy due to mechanical overloading placed on the tendon., Competing Interests: The authors have declared that no competing interests exist.

Because of limitations in the current understanding of the exact pathogenesis of tendinopathy, and the lack of an optimal experimental model, effective therapy for the disease is currently unavailable. This study aims to prove that repression of oxidative stress modulates the differentiation of tendon-derived cells (TDCs) sustaining excessive tensile strains, and proposes a novel bioreactor capable of applying differential tensile strains to cultured cells simultaneously. TDCs, including tendon-derived stem cells, tenoblasts, tenocytes, and fibroblasts, were isolated from the patellar tendons of Sprague‒Dawley rats. Cyclic uniaxial stretching with 4% or 8% strain at 0.5 Hz for 8 h was applied to TDCs. TDCs subjected to 8% strain were treated with epigallocatechin gallate (EGCG), piracetam, or no medication. Genes representing non-tenocyte lineage ( Pparg , Sox9 , and Runx2 ) and type I and type III collagen were analyzed by quantitative polymerase chain reaction. The 8% strain group showed increased expression of non-tenocyte lineage genes and type III/type I collagen ratios compared with the control and 4% strain groups, and the increased expression was ameliorated with addition of EGCG and piracetam. The model developed in this work could be applied to future research on the pathophysiology of tendinopathy and development of treatment options for the disease. Repression of oxidative stress diminishes the expression of genes indicating aberrant differentiation in a rat cell model, which indicates potential therapeutic intervention of tendinopathy, the often relentlessly degenerate condition.

Background: As a recognized cause of groin pain following total hip arthroplasty, iliopsoas tendonitis probably results from different factors. Given the anatomic disadvantage, dysplastic hips theoretically make acetabular component relatively retroverted or oversized, screws implanted frequently, and iliopsoas tendonitis more likely. However, the prevalence and mechanism of iliopsoas tendonitis following total hip replacement in dysplastic hips are not fully understood., Methods: One hundred and thirty-three total hip arthroplasties for Crowe type 2 to 4 dysplastic hips were compared with 126 total hip arthroplasties for hips without dysplasia in this study. Preoperative patient demographic data were well matched between the groups. Clinical and radiographic evaluations were performed., Results: A significantly higher frequency of protruded screws (24.8% vs 0), anterior overhang of acetabular components (30.8% vs 4.0%), and increased leg lengthening (3.6 [2.0-6.8] vs 0.5 [0-1.8]) was found in the dysplastic group (all p values < 0.05). However, the femoral offset and inclination and anteversion of acetabular components between the groups did not differ significantly. No difference in the prevalence of iliopsoas tendonitis was found between the groups. A new cause of iliopsoas tendonitis following total hip arthroplasty was detected in the dysplastic group. The iliopsoas tendonitis was irritated by an instable artificial femoral head., Conclusions: The dysplastic hips did not present a higher incidence of postoperative iliopsoas tendonitis in this study. Iliopsoas tendonitis could be somewhat prevented by smaller size of acetabular components and soft tissue release in dysplastic hips, but irritated by an instable artificial femoral head.

Impingement of hip arthroplasty components on soft tissues may adversely affect outcomes. An example is impingement of the cup on the ilio-psoas tendon, which has been reported in 0.4% to 8.3% of patients. Contributors to ilio-psoas tendon impingement (IPTI) can be categorised as anatomic (hypoplastic anterior wall), technical (inadequate anteversion and/or lower inclination, oversized cup, cement in contact with the tendon, and intra-muscular screw), and prosthetic (e.g., aggressive cup design, large-diameter head, resurfacing, and collared femoral prosthesis). IPTI manifests as groin pain, raising diagnostic challenges since this symptom lacks specificity. Physical findings of value for the diagnosis include pain exacerbation during active hip flexion, groin pain upon straight-leg raise to 30°, and/or snapping hip syndrome. Confirmation is then provided by ultrasonography and, most importantly, computed tomography. Once the diagnosis is confirmed, non-operative treatment combining physical therapy and local corticosteroid injections is prescribed. When these measures fail, endoscopic or arthroscopic surgery is generally effective. In patients with major cup malposition, revision of the cup is the preferred option, despite the higher complication rate. When cup position is adequate, ilio-psoas tenotomy can be performed either extra-articularly at the lesser trochanter (by endoscopy) or intra-articularly (by arthroscopy). The arthroscopic technique is more demanding but useful when the diagnosis is in doubt, as it allows examination of the prosthetic bearing surfaces. Both techniques and the risks inherent in each are discussed in detail. Tenotomy, whether performed endoscopically or arthroscopically, promptly provides good outcomes in over 85% of patients, usually with full recovery of hip flexor strength over time. These minimally invasive techniques, while as effective as conventional surgery, are associated with lower morbidity rates., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)