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The Orthopaedic Section of the American Physical Therapy Association (APTA) has an ongoing effort to create evidence-based practice guidelines for orthopaedic physical therapy management of patients with musculoskeletal impairments described in the World Health Organization's International Classification of Functioning, Disability, and Health (ICF). The purpose of these revised clinical practice guidelines is to review recent peer-reviewed literature and make recommendations related to midportion Achilles tendinopathy. J Orthop Sports Phys Ther 2018;48(5):A1-A38. doi:10.2519/jospt.2018.0302.

Tendinopathy, an important sports injury afflicting athletes and general public, is associated with huge economic losses. The currently used diagnostic tests are subjective, show moderate sensitivity and specificity; while treatment failures persist despite advances in therapy. This highlights the need for tendinopathy diagnostic and treatment monitoring tools. This study investigates tendon injury, natural healing and effect of treatment using ATR-FTIR complemented with histopathology. Control (C), injured (I) and treated (T) rat tendons were extracted 3, 7, 14 and 28 days post-injury/treatment, representing phases of healing; and subjected to hematoxylin & eosin staining as well as spectroscopy. While C showed no change, I- and T-related histological changes could be clearly observed in stained sections. ATR-FTIR spectra highlighted the biochemical changes within groups. Multivariate analysis could classify C, I and T with 75%; different days between groups with 84%; and different days within group with 65% efficiency. Results suggest that such analysis can not only identify C, I or T but also different phases of healing. Difference between I and T at different time points also suggest change in rate of healing. Further studies may help develop this technique for clinical diagnosis and treatment monitoring in future., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Recent investigation of human tissue and cells from positional tendons such as the rotator cuff has clarified the importance of inflammation in the development and progression of tendon disease. These mechanisms remain poorly understood in disease of energy-storing tendons such as the Achilles. Using tissue biopsies from patients, we investigated if inflammation is a feature of Achilles tendinopathy and rupture., Methods: We studied Achilles tendon biopsies from symptomatic patients with either mid-portion tendinopathy or rupture for evidence of abnormal inflammatory signatures. Tendon-derived stromal cells from healthy hamstring and diseased Achilles were cultured to determine the effects of cytokine treatment on expression of inflammatory markers., Results: Tendinopathic and ruptured Achilles highly expressed CD14+ and CD68+ cells and showed a complex inflammation signature, involving NF-κB, interferon and STAT-6 activation pathways. Interferon markers IRF1 and IRF5 were highly expressed in tendinopathic samples. Achilles ruptures showed increased PTGS2 and interleukin-8 expression. Tendinopathic and ruptured Achilles tissues expressed stromal fibroblast activation markers podoplanin and CD106. Tendon cells isolated from diseased Achilles showed increased expression of pro-inflammatory and stromal fibroblast activation markers after cytokine stimulation compared with healthy hamstring tendon cells., Conclusions: Tissue and cells derived from tendinopathic and ruptured Achilles tendons show evidence of chronic (non-resolving) inflammation. The energy-storing Achilles shares common cellular and molecular inflammatory mechanisms with functionally distinct rotator cuff positional tendons. Differences seen in the profile of ruptured Achilles are likely to be attributable to a superimposed phase of acute inflammation and neo-vascularisation. Strategies that target chronic inflammation are of potential therapeutic benefit for patients with Achilles tendon disease., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To assess the differences in morphology and alignment of the knee between patients with proximal patellar tendinopathy (PPT) and a control group, using MRI and focusing on the patellofemoral joint., Methods: We retrospectively included 35 patients with clinically diagnosed and unequivocal findings of PPT on knee MRI, the case group. For the control group, we included 70 patients who underwent knee MRI for other reasons, with no clinical or MRI evidence of PPT. Patients and controls were matched for age and gender, with all subjects reporting frequent physical activity. MRIs were evaluated by two musculoskeletal radiologists, who assessed parameters of patellar morphology, trochlear morphology, patellofemoral alignment, and tibiofemoral alignment. The differences in parameters between cases and controls were assessed using Student's t test. Logistic regression was applied to assess the associations between the MRI parameters and the presence of PPT., Results: The patellar height Insall-Salvati ratio was different between cases and controls (1.37 ± 0.21 vs. 1.24 ± 0.19; p = 0.003). The subchondral Wiberg angle was higher in cases than controls (136.8 ± 7.4 vs. 131.7 ± 8.8; p = 0.004). After applying logistic regression, significant associations with PPT were found [odds ratios (95% CI)] for patellar morphology [1.1 (1.0, 1.2)] and patellar height [1.3 (1.0, 1.7)]., Conclusions: Patellar height and the subchondral patellar Wiberg angle were greater in patients with PPT and significantly associated with PPT.

Our goal was to develop a novel technique for inducing Achilles tendinopathy in animal models which more accurately represents the progressive histological and biomechanical characteristic of chronic Achilles tendinopathy in humans. In this animal research study, forty-five rabbits were randomly assigned to three groups and given bilateral Achilles injections. Low dose (LD group) (n = 18) underwent a novel technique with three low-dose (0.1mg) injections of collagenase that were separated by two weeks, the high dose group (HD) (n = 18) underwent traditional single high-dose (0.3mg) injections, and the third group were controls (n = 9). Six rabbits were sacrificed from each experimental group (LD and HD) at 10, 12 and 16 weeks. Control animals were sacrificed after 16 weeks. Histological and biomechanical properties were then compared in all three groups. At 10 weeks, Bonar score and tendon cross sectional area was highest in HD group, with impaired biomechanical properties compared to LD group. At 12 weeks, Bonar score was higher in LD group, with similar biomechanical findings when compared to HD group. After 16 weeks, Bonar score was significantly increased for both LD group (11,8±2,28) and HD group (5,6±2,51), when compared to controls (2±0,76). LD group showed more pronounced histological and biomechanical findings, including cross sectional area of the tendon, Young's modulus, yield stress and ultimate tensile strength. In conclusion, Achilles tendinopathy in animal models that were induced by serial injections of low-dose collagenase showed more pronounced histological and biomechanical findings after 16 weeks than traditional techniques, mimicking better the progressive and chronic characteristic of the tendinopathy in humans.

Objective: To investigate the correlation between MRI, clinical tests, histopathologic features of posterior tibial tendon (PTT) dysfunction in patients with acquired adult flatfoot deformity surgically treated with medializing calcaneal osteotomy and flexor digitorum longus tendon transposition., Materials and Methods: Nineteen patients (11 females; age: 46 ± 15 year, range 18-75) were pre-operatively evaluated using the single heel rise (HR) and the first metatarsal rise (FMR) sign tests. Two reviewers graded the PTT tears on a I-III scale and measured the hindfoot valgus angle on the pre-operative MRI of the ankle. The specimens of the removed portion of PTT were histologically analysed by two pathologists using the Bonar and Movin score. Linear regression, Spearman's rank-order, and intraclass correlation coefficient (ICC) statistics were used., Results: ICC for MRI was excellent (0.952). Correlation between FMR and HR tests was at limit of significance (r = 0.454; P = 0.051). The HR and FMR tests were significantly correlated to the Movin score (r = 0.581; P = 0.009 and r = 0.538; P = 0.018, respectively) and were not significantly correlated to the Bonar score (both with a r = 0.424; P = 0.070). PTT tendinopathy grading at MRI was significantly correlated to the FMR test (p = 0.041) but not to the hindfoot valgus angle (p = 0.496), the HR test (p = 0.943), the Bonar score (p = 0.937), and the Movin score (p = 0.436). The hindfoot angle was not correlated to any of the other variables (p > 0.264)., Conclusion: For PTT dysfunction, there is high correlation between HR and FMR test and histology evaluated using the Movin score, while no correlation was seen for the Bonar score. Semiquantitative grading of PTT dysfunction at MRI only correlates to the FMR and not to histology. The hindfoot valgus angle is not correlated to any of the considered variables., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Reasons for the development of chronic tendon pathologies are still under debate and more basic knowledge is needed about the different diseases. The aim of the present study was therefore to characterize different acute and chronic Achilles tendon disorders. Achilles tendon samples from patients with chronic tendinopathy ( n = 7), chronic ruptures ( n = 6), acute ruptures ( n = 13), and intact tendons ( n = 4) were analyzed. The histological score investigating pathological changes was significantly increased in tendinopathy and chronic ruptures compared to acute ruptures. Inflammatory infiltration was detected by immunohistochemistry in all tendon pathology groups, but was significantly lower in tendinopathy compared to chronic ruptures. Quantitative real-time PCR (qRT-PCR) analysis revealed significantly altered expression of genes related to collagens and matrix modeling/remodeling (matrix metalloproteinases, tissue inhibitors of metalloproteinases) in tendinopathy and chronic ruptures compared to intact tendons and/or acute ruptures. In all three tendon pathology groups markers of inflammation ( interleukin ( IL ) 1β , tumor necrosis factor α , IL6 , IL10 , IL33 , soluble ST2 , transforming growth factor β1 , cyclooxygenase 2 ), inflammatory cells ( cluster of differentaition ( CD ) 3 , CD68 , CD80 , CD206 ), fat metabolism ( fatty acid binding protein 4 , peroxisome proliferator-activated receptor γ , CCAAT/enhancer-binding protein α , adiponectin ), and innervation (protein gene product 9.5 , growth associated protein 43 , macrophage migration inhibitory factor ) were detectable, but only in acute ruptures significantly regulated compared to intact tendons. The study gives an insight into structural and molecular changes of pathological processes in tendons and might be used to identify targets for future therapy of tendon pathologies., Competing Interests: The authors declare no conflict of interest.

Calcific tendinopathy of the rotator cuff is a common cause of shoulder pain. Inflammation of the rotator cuff tendons may be complicated by adjacent bone erosion and subsequent migration of calcific deposits within the bone resulting in marrow inflammation. Bone marrow involvement is not readily visible using X-ray and ultrasound (US) and further testing is necessary. Magnetic resonance imaging (MRI) is a highly sensitive technique that can detect a focal bone T1 and T2-weighted hypointensity with bone marrow edema-like signal and cortical erosion. These findings can mislead the radiologist by suggesting an infectious or neoplastic lesion, often requiring further evaluation with computed tomography (CT) and biopsy. We report two cases of patients with shoulder pain in which different radiological approaches were used with pathological confirmation in one of them. In the first case, MRI revealed significant bone involvement in the head of the humerus and cortical erosion of the greater tuberosity. A CT examination and a biopsy was necessary for a final diagnosis of inflammatory bone reaction from intraosseous migration of tendinous calcifications. In the second case, similar MRI findings prompted re-evaluation of imaging to make a diagnosis of intraosseous migration of tendinous calcifications, obviating the need to perform CT and biopsy. We illustrate MRI signs of this complication that we think would allow to narrow the differential diagnosis potentially avoiding biopsy and additional CT examinations.

Tendons are connective tissue structures of paramount importance to human ability of locomotion. The understanding of their physiology and pathology is gaining importance as advances in regenerative medicine are being made today. So far, very few studies were conducted to extend the knowledge about pathology, healing response and management of tendon lesions. In this paper we summarise actual knowledge on structure, process of healing and ageing of the tendons. The structure of tendon is optimised for the best performance of the tissue. Despite the simplicity of the healing response, numerous studies showed that the problems with full recovery are common and much more significant than we thought; that is why we discussed the issue of immobilisation and mechanical stimulation during healing process. The phenomenon of tendons' ageing is poorly understood. Although it seems to be a natural and painless process, it is completely different from degeneration in tendinopathy. Recent studies of biological treatment reported faster and optimal healing of the tendons when augmented by growth factors and stem cells. Despite advances in biology of tendons, management of their injuries is still a challenge for physicians; therefore, further studies are required to improve treatment outcomes.

Background: High-grade partial-thickness rotator cuff tears (hPTRCTs) are frequently encountered in the shoulder. However, little information is available on the prevalence or timing of tear progression. Purpose/Hypothesis: The purpose was to prospectively evaluate the structural progression of hPTRCTs with a minimum follow-up of 1 year using magnetic resonance imaging (MRI). The hypothesis was that a substantial portion of hPTRCT patients would experience tear progression or evolution to a full-thickness rotator cuff tear., Study Design: Case series; Level of evidence, 4., Methods: Between May 2010 and December 2015, 362 patients were diagnosed with hPTRCT (tear involvement >50% of the mediolateral length of the footprint) of the supraspinatus and were treated nonoperatively. Among these patients, 81 underwent follow-up MRI at least 1 year after initial presentation, and these patients were included in the final analysis. Initial and follow-up MRIs were used to determine whether tears had improved, had not changed, or had progressed. A change in tear involvement of >20% was defined as a significant change. Patients were categorized as follows: (1) a decrease in tear involvement of >20% (improved), (2) an increase or decrease of ≤20% (no change), or (3) an increase in tear involvement of >20% (progressed). Demographic data and morphologic data were analyzed to identify variables related to tear progression. Among them, severity of tendinosis was graded using MRIs: grade 1 (mild tendinosis), mild focal increase in tendon signal; grade 2 (moderate tendinosis), moderate focal increase in tendon signal; and grade 3 (marked tendinosis), marked generalized increase in tendon signal., Results: At initial diagnosis, 23 were articular-side (28%) and 58 were bursal-side (72%) hPTRCTs. The study cohort was composed of 51 women and 30 men, and the mean patient age was 62.3 years (range, 41-77 years). Follow-up MRI was performed at a mean 19.9 ± 10.9 months (range, 12-52 months). A significant change in tear involvement was observed at follow-up. In 13 patients (16%, 2 articular-side and 11 bursal-side tears), tears were classified as progressed (the progressed group); in 48 patients (59%), tears exhibited no change (the unchanged group); and in 20 patients (25%, 9 articular-side and 11 bursal-side tears), tears were improved (the improved group). Univariate analysis showed initial tendinosis grade was significantly different in the 3 groups (grade 1, 2, and 3: 5, 4, and 4 in progressed; 36, 11, and 1 in unchanged; 10, 8, and 2 in improved group, respectively, P = .007)., Conclusion: Although progression of hPTRCT in the long term is uncertain, after 1-year follow-up with MRI, tears progressed in 16% of the tears in this study. Furthermore, some tears were healed or reduced in size, which indicates that decisions to undertake surgical repair at time of presentation may be excessive.

Background: Tendinopathy of the long head of the biceps brachii tendon (LHBT) is one of the most common, painful conditions of the anterior part of the shoulder and often coexists with rotator cuff tears. Multifactorial aetiopathology of tendi-nopathy is poorly understood; however, several studies indicated that it is seen predominantly in areas with decreased vascularity of the tissue; the pathology is also characterised by expansive and abundant neovascular in-growth. The aim of the study was to investigate the relationship between the neovascularisation of proximal part of the LHBT and pain along the bicipital groove., Materials and Methods: Tissue material was obtained from 28 patients who underwent a shoulder arthroscopy and experienced pain along the bicipital groove measured using Visual-Analog Scale (VAS) score. CD31 and CD34 molecules were visualised by immunohistochemical method to assess biceps tendon neovascula-risation and quantify it based on a Bonar scoring system., Results: Although all patients reported pain prior to arthroscopy (mean VAS score was 7.5), microscopic examination did not reveal neovascularisation in all cases. Immunohistochemical staining for CD31 and CD34 allowed for very precise visualisation and quantification of neovascularisation; however there was also no correlation between vessels in-growth scores and pain., Conclusions: The obtained data suggest that neovascularisation process in tendino-pathy is not directly related to pain; however, further studies are needed to explain its significance in the LHBT tendinopathy. (Folia Morphol 2018; 77, 2: 378-385).

To investigate the mechanism of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and human adipose-derived stem cells (hADSCs) in the treatment of Achilles tendinitis. Biomechanical indices of stiffness, stress, and maximum load-to-failure were detected by biomechanical test. mRNA and protein levels of miR-363, p-PI3K/AKT, tendon-related genes Collagen I, Scleraxis (Scx), and Tenascin C (TNC) were measured by qRT-PCR and western blot. The proliferation of hADSCs was accessed by MTT assay. Biomechanical indices of stiffness, stress, and maximum load-to-failure, and mRNA and protein levels of tendon-related genes could be improved by rhPDGF-BB or hADSCs alone, and could be further improved by rhPDGF-BB + hADSCs. rhPDGF-BB and hADSCs downregulated the expression of miR-363 and upregulated the levels of p-PI3K/Akt, and rhPDGF-BB + hADSCs further strengthened these effects. In addition, rhPDGF-BB promoted the proliferation of hADSCs in vitro and upregulated the expression of tendon-related genes. miR-363 mimic downregulated the levels of p-PI3K/Akt, miR-363 inhibitor upregulated the levels of p-PI3K/Akt, and miR-363 mimic and PI3K/Akt pathway inhibitor LY294002 reversed the positive effect of rhPDGF-BB on the proliferation of hADSCs, which suggested that rhPDGF-BB promoted the proliferation of hADSCs via miR-363/PI3K/Akt pathway. Biomechanical indices and tendon-related genes could be improved by rhPDGF-BB and hADSCs. Moreover, rhPDGF-BB promoted the proliferation of hADSCs via miR-363/PI3K/Akt pathway, indicating that rhPDGF-BB combined with ADSCs could treat Achilles tendinitis via miR-363/PI3K/Akt pathway.

Tendinopathic tissue has long been characterized by changes to collagen microstructure. However, initial tendon damage from excessive mechanical loading-a hallmark of tendinopathy development-could occur at the nanoscale level of collagen fibrils. Indeed, it is on this scale that tenocytes interact directly with tendon matrix, and excessive collagen fibril damage not visible at the microscale could trigger a degenerative cascade. In this study, we explored whether initiation of tendon damage during cyclic loading occurs via a longitudinal compression-induced buckling mechanism of collagen fibrils leading to nanoscale kinkband development. Two groups of tendons were cyclically loaded to equivalent peak stresses. In each loading cycle, tendons in one group were unloaded to the zero displacement mark, while those in the other group were unloaded to a nominal level of tension, minimizing the potential for fibril buckling. Tendons that were unloaded to the zero displacement mark ruptured significantly sooner during cyclic loading (1,446 ± 737 vs. 4,069 ± 1,129 cycles), indicating that significant fatigue damage is accrued in the low stress, toe region of the load-deformation response. Ultrastructural analysis using scanning electron microscopy of tendons stopped after 1,000 cycles showed that maintaining a nominal tension slowed the accumulation of kinkbands, supporting a longitudinal compression-induced buckling mechanism as the basis for kinkband development. Based on our results, we present a new descriptive model for the initiation of tendon damage during cyclic loading. The so-called Compression of Unrecovered Elongation or CUE Model may provide useful insight into the development of tendinopathy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:467-476, 2018., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: The ultrastructural alterations related to tendinopathy have not been well described. Most studies on this subject have been conducted many years ago and focused on material from the Achilles tendon. It was demonstrated that various comorbidities can affect ultrastructural alterations in the advanced tendinopathy; however, there is very little data on ultrastructural morphology in tendinopathies related to mechanical overload as in case of the long head of the biceps brachii tendon (LHBT). The aim was to determine intermediate ultrastructural alterations in middle to severe grade the LHBT tendinopathy and to establish if they are different than those reported in the literature for other anatomical locations., Materials and Methods: In this study we examined the ultrastructure of a series of the LHBT fragments arthroscopically removed due to tendinopathy and inve-stigated the morphology of tenocytes and collagen fibres in cases of the LHBT tendinopathy., Results: In pathological samples tenocytes were randomly scattered, their shape was round and the shape of nuclei was also disrupted. The presence of apoptotic--like features in tenocytes' nuclei was noted. All samples showed replacement of collagen fibrils by non-collagen extracellular matrix and diffuse collagen disorganisation., Conclusions: It was demonstrated at ultrastructural level that the LHBT tendino-pathy is not simply a wear and tear phenomenon, since chronic degeneration of the extracellular matrix and tenocytes were present, similarly as in tendinopathies, in other anatomical locations. (Folia Morphol 2018; 77, 2: 371-377).

During acute inflammatory phases of tendinopathy, a combination of physical therapy and corticosteroid injections is considered to be moderately effective for acute inflammation. However, surgical debridement of tendinopathic tissues is often required for chronic cases. The TenJet system created by HydroCision, Inc. is a percutaneous device that uses high-pressure saline to debride pathologic tissues during tenotomy. Here, we use a collagenase-induced tendinopathy model on explants from bovine ankle extensor tendons. We use the volume of defect debrided as a metric to determine the efficacy of using high-velocity fluid flow as a debridement tool as well as the effect of velocity magnitude on efficacy. Furthermore, we highlight the negligible disruption of healthy tissue surrounding pathologic tissue.

Although the incidence of midportion Achilles tendinopathy is under 1% in the general population, it is quite a common disease in runners that is characterized by the symptom triad of pain, swelling and impaired physical performance. Pain and swelling are located in the area 2 to 7 cm proximal the tendon insertion onto the calcaneus.Diagnosis is made by adequate clinical symptoms and corresponding findings in sonography and/or magnetic resonance imaging scans. Histopathologically, mostly degenerative changes in the tendon structure are found, sometimes accompanied by intra- and paratendinous inflammation.Treatment options are conservative or surgical, but conservative ones should be tried first. The best evidence is available for eccentric exercise protocols, which represent the gold standard in conservative treatment options, followed by extracorporal shockwave (ECSW) therapy and corticoid injections.In about 25% of all cases, because of unsatisfactory nonoperative treatment results, surgery is recommended. Open, minimally invasive as well as tenoscopic methods exist, which show patients' satisfactory rates of about 80%. The return to sport or full physical performance is variable and may take up to 18 months for both treatment regimens.

Background: Glenohumeral exploration is routinely performed during arthroscopic removal of rotator cuff calcifications in patients with calcific tendinitis of the shoulder (CTS). However, evidence on the prevalence of intraarticular co-pathologies is lacking and the benefit of glenohumeral exploration remains elusive. The aim of the present study was to assess and quantify intraoperative pathologies during arthroscopic removal of rotator cuff calcifications in order to determine whether standardized diagnostic glenohumeral exploration appears justified in CTS patients., Methods: One hundred forty five patients undergoing arthroscopic removal of calcific depots (CD) that failed conservative treatment were included in a retrospective cohort study. Radiographic parameters including number/localization of calcifications and acromial types, intraoperative arthroscopic findings such as configuration of glenohumeral ligaments, articular cartilage injuries, and characteristics of calcifications and sonographic parameters (characteristics/localization of calcification) were recorded., Results: One hundred forty five patients were analyzed. All CDs were removed by elimination with a blunt hook probe via "squeeze-and-stir-technique" assessed postoperatively via conventional X-rays. Neither subacromial decompression nor refixation of the rotator cuff were performed in any patient. Prevalence of glenohumeral co-pathologies, such as partial tears of the proximal biceps tendon (2.1%), superior labral tears from anterior to posterior (SLAP) lesions (1.4%), and/or partial rotator cuff tears (0.7%) was low. Most frequently, glenohumeral articular cartilage was either entirely intact (ICRS grade 0 (humeral head/glenoid): 46%/48%) or showed very mild degenerative changes (ICRS grade 1: 30%/26%). Two patients (1.3%) required intraarticular surgical treatment due to a SLAP lesion type III (n = 1) and an intraarticular rupture of CD (n = 1)., Conclusions: Routine diagnostic glenohumeral exploration does not appear beneficial in arthroscopic treatment of CTS due to the low prevalence of intraarticular pathologies which most frequently do not require surgical treatment. Exploration of the glenohumeral joint in arthroscopic removal of CD should only be performed in case of founded suspicion of relevant concomitant intraarticular pathologies.

Since its introduction, susceptibility-weighted-magnetic resonance imaging (SW-MRI) has shown the potential to overcome the insensitivity of MRI to calcification. Previous studies reporting the diagnostic performance of SW-MRI and magnetic resonance imaging (MRI) for the detection of calcifications are inconsistent and based on single-institution designs. To our knowledge, this is the first meta-analysis on SW-MRI, determining the potential of SW-MRI to detect calcifications. Two independent investigators searched MEDLINE, EMBASE and Web of Science for eligible diagnostic accuracy studies, which were published until March 24, 2017 and investigated the accuracy of SW-MRI to detect calcifications, using computed tomography (CT) as a reference. The QUADAS-2 tool was used to assess study quality and methods for analysis were based on PRISMA. A bivariate diagnostic random-effects model was applied to obtain pooled sensitivities and specificities. Out of the 4629 studies retrieved by systematic literature search, 12 clinical studies with 962 patients and a total of 1,032 calcifications were included. Pooled sensitivity was 86.5% (95%-confidence interval (CI): 73.6-93.7%) for SW-MRI and 36.7% (95%-CI:29.2-44.8%) for standard MRI. Pooled specificities of SW-MRI (90.8%; 95%-CI:81.0-95.8%) and standard MRI (94.2; 95%-CI:88.9-96.7%) were comparable. Results of the present meta-analysis suggest, that SW-MRI is a reliable method for detecting calcifications in soft tissues.

Excessive mechanical loading is a major factor affecting heterotopic ossification (HO), which is a major pathological alteration in calcific tendinopathy. However, physical therapies with mechanical loading as the functional element have exhibited promising results in the treatment of calcific tendinopathy. The dual effects that mechanical loading may have on the pathogenesis and rehabilitation of calcified tendinopathy remain unclear. The present study was designed to investigate the effects of mechanical loading on HO in calcific tendinopathy. In the present study, a tendon cell in vitro stretch model and an Achilles tenotomy rat model were used to simulate different elongation mechanical loading scenarios in order to investigate the effects of mechanical loading on HO of the tendon. In addition, rapamycin, a selective mammalian target of rapamycin complex‑1 (mTORC1) signaling pathway inhibitor, was employed to determine whether mechanical loading modulates heterotopic ossification in calcific tendinopathy through the mTORC1 signaling pathway. The data indicate that mechanical loading modulated HO of the tendon through the mTORC1 signaling pathway, and that low elongation mechanical loading attenuated HO, while high elongation mechanical loading accelerated HO in vivo. This study may improve the understanding of the effect of physical therapies used to treat calcific tendinopathy, so as to guide clinical treatment more effectively. Furthermore, rapamycin may be a potential drug for the treatment of calcific tendinopathy.

OBJECTIVE To evaluate the effect of track surface firmness on the development of musculoskeletal injuries in French Trotters during 4 months of race training. ANIMALS 12 healthy 3-year-old French Trotters. PROCEDURES Horses were paired on the basis of sex and body mass. Horses within each pair were randomly assigned to either a hard-track or soft-track group. The counterclockwise training protocol was the same for both groups. Surface firmness of each track was monitored throughout the training period. Radiography, ultrasonography, MRI, and scintigraphy were performed on all 4 limbs of each horse before and after 2 and 4 months of training. Lesions were described, and lesion severity was classified with a 5-point system, where 0 = no lesions and 4 = severe lesion. RESULTS 86 lesions were identified, of which 46 (53.5%) were classified as potentially clinically relevant (grade, ≥ 2). Of the 18 moderate and severe lesions, 15 were identified in horses of the hard-track group, and 10 of those were in forelimbs. Moderate to severe tendinopathy of the superficial digital flexor tendon of the forelimb developed in 3 of the 6 horses of the hard-track group but none of the horses of the soft-track group. Metatarsal condyle injuries were more frequent in horses of the hard-track group than horses of the soft-track group. Severe lesions were identified only in left limbs. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that track surface firmness is a risk factor for musculoskeletal injuries in horses trained for harness racing.

Flexor tendinopathy is a common problem affecting humans and animals. Tendon healing is poorly understood and the outcomes of conservative and surgical management are often suboptimal. While often considered a localized injury, recent evidence indicates that in the short term, tendinopathic changes are distributed widely throughout the tendon, remote from the lesion itself. Whether these changes persist throughout healing is unknown. The aim of this study was to document gene expression, histopathological and biomechanical changes that occur throughout the superficial digital flexor tendon (SDFT) up to 16 weeks post-injury, using an ovine surgical model of tendinopathy. Partial tendon transection was associated with decreased gene expression for aggrecan, decorin, fibromodulin, tissue inhibitors of metalloproteinases (TIMPS 1, 2 and 3), collagen I and collagen II. Gene expression for collagen III, lumican and matrix metalloproteinase 13 (MMP13) increased locally around the lesion site. Expression of collagen III and MMP13 decreased with time, but compared to controls, collagen III, MMP13 and lumican expression remained regionally high throughout the study. An increase in TIMP3 was observed over time. Histologically, operated tendons had higher pathology scores than controls, especially around the injured region. A chondroid phenotype was observed with increased cellular rounding and marked proteoglycan accumulation which only partially improved with time. Biomechanically, partial tendon transection resulted in a localized decrease in elastic modulus (in compression) but only at 8 weeks postoperatively. This study improves our understanding of tendon healing, demonstrating an early 'peak' in pathology characterized by altered gene expression and notable histopathological changes. Many of these pathological changes become more localized to the region of injury during healing. Collagen III and MMP13 expression levels remained high close to the lesion throughout the study and may reflect the production of tendon tissue with suboptimal biomechanical properties. Further studies evaluating the long-term response of tendon to injury (6-12 months) are warranted to provide additional information on tendon healing and provide further understanding of the mechanisms underlying the pathology observed in this study.

Objective: To assess the correlation between magnetic resonance and ultrasound findings and clinical outcome after intratendinous injection of leucocyte-rich platelet-rich plasma or adipose-derived stromal vascular fraction in patients with non-insertional Achilles tendinopathy., Materials and Methods: Forty-three patients (age: 47.8±5.1, range 29-55) with unilateral or bilateral non-insertional Achilles tendinopathy (58 tendons overall) were randomly assigned to platelet-rich plasma (22 patients, 28 tendons) or adipose-derived stromal vascular fraction (21 patients, 30 tendons) injection group. All patients underwent magnetic resonance (tendon cross-sectional area, signal intensity, maximum anteroposterior thickness were measured), ultrasound (maximum anteroposterior thickness, power Doppler signal, ultrasound gray scale echotexture were measured), and visual analogue scale (VAS) pain evaluation at baseline and at six months from treatment. Wilcoxon, intraclass correlation coefficient, repeated measure ANOVA tests were used., Results: There was a significant (P<0.001) decrease of mean VAS from pre-treatment (6.4±1.4) to six-month evaluation (1.8±1.7). Significant increase of tendon thickness measured using magnetic resonance (P=0.013) and ultrasound (P=0.012) and power Doppler signal (P=0.027) was seen. There was no significant difference between pre- and post-treatment cross sectional area, signal intensity, and echotexture (P>0.217). None of the pre-treatment parameters was a predictor of treatment outcome (P>0.104). There was an excellent agreement between tendon thickness measurement between magnetic resonance and ultrasound (intraclass correlation coefficient=0.986) CONCLUSIONS: Both treatments seem to allow for clinical benefit, associated to early slight increase of tendon size and power Doppler signal. Imaging cannot be used as a predictor of clinical outcome., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to evaluate whether glenohumeral arthroscopy is an appropriate gold standard for the diagnosis of long head of biceps (LHB) tendon pathology. The objectives were to evaluate whether the length of tendon that can be seen at arthroscopy allows visualisation of areas of predilection of pathology and also to determine the rates of missed diagnoses at arthroscopy when compared to an open approach., Methods: A systematic review of cadaveric and clinical studies was performed. The search strategy was applied to MEDLINE, PubMed and Google Scholar databases. All relevant articles were included. Critical appraisal of clinical studies was performed using a validated quality assessment scale., Results: Five articles were identified for inclusion in the review. This included both clinical and cadaveric studies. The overall population comprised 18 cadaveric specimens and 575 patients. Out of the five included studies, three reported the length of LHB tendon visualised during arthroscopy and four reported the rate of missed LHB diagnosis. Cadaveric studies showed that the use of a hook probe allowed arthroscopic visualisation of between 34 and 48 % of the overall length of the LHB. In the clinical series, the rate of missed diagnoses at arthroscopy when compared to open exploration ranged between 33 and 49 %., Conclusions: Arthroscopy allows visualisation of only a small part of the extra-articular LHB tendon. This leads to a high rate of missed pathology in the distal part of the tendon. Published figures for sensitivities and specificities of common physical examination and imaging tests for LHB pathology that are based on arthroscopy as the gold standard are therefore invalid. In clinical practice, it is important to note that a "negative" arthroscopic assessment does not exclude a lesion of the LHB tendon as this technique does not allow visualisation of common sites of distal pathology., Level of Evidence: IV.

Background: In various Achilles tendon disorders, little attention is paid to the bone environment at the tendon insertion sites. The aim of the present study was to assess the calcaneal bone structure in Achilles tendon disorders using computed tomography (CT)., Methods: This study included 31 male patients diagnosed with various Achilles disorders, including episodes of tendon rupture (TR), conservatively treated tendinopathy (TP), and critical-stage Achilles TP treated with endoscopic surgery (TS). CT scans of both feet were conducted to assess the calcaneal bone structure in the TP and TS groups, which comprised 23 patients. Bone measurements were calculated, including the bone volume-to-total volume ratio (BV/TV), cross-sectional area (CSA), product moment of area (Ipm), and polar section modulus (Zpol)., Results: The results demonstrated increased BV/TV, CSA, Ipm, and Zpol values in patients who underwent tendinoscopy and in patients with insertional TP., Conclusions: CT images are useful for evaluating calcaneal trabecular structural alterations in patients with Achilles pathology and correlate with the TP type.

The mechanisms underpinning the failure of inflammation to resolve in diseased musculoskeletal soft tissues are unknown. Herein, we studied bioactive lipid mediator (LM) profiles of tendon-derived stromal cells isolated from healthy donors and patients with chronic tendinopathy. Interleukin(IL)-1β treatment markedly induced prostaglandin biosynthesis in diseased compared to healthy tendon cells, and up regulated the formation of several pro-resolving mediators including 15-epi-LXA 4 and MaR1. Incubation of IL-1β stimulated healthy tendon cells with 15-epi-LXA 4 or MaR1 down-regulated PGE 2 and PGD 2 production. When these mediators were incubated with diseased cells, we only found a modest down regulation in prostanoid concentrations, whereas it led to significant decreases in IL-6 and Podoplanin expression. In diseased tendon cells, we also found increased 15-Prostaglandin Dehydrogenase (15-PGDH) expression as well as increased concentrations of both 15-epi-LXA 4 and MaR1 further metabolites, 15-oxo-LXA 4 and 14-oxo-MaR1. Inhibition of 15-PGDH using either indomethacin or SW033291 significantly reduced the further conversion of 15-epi-LXA 4 and MaR1 and regulated expression of IL-6, PDPN and STAT-1. Taken together these results suggest that chronic inflammation in musculoskeletal soft tissues may result from dysregulated LM-SPM production, and that inhibition of 15-PGDH activity together with promoting resolution using SPM represents a novel therapeutic strategy to resolve chronic tendon inflammation.

Tendinopathy of the long head of the biceps (TLHB) involves various types of extracellular matrix degeneration, but previous studies have not evaluated elastic fibers. The purpose of this study was to investigate elastic fiber distribution in long head of the biceps (LHB). The TLHB tendons of 16 consecutive patients (eight men and eight women; average age of 55.75 years; age range of 40-71 years) were transected and harvested. Three cadaveric LHB tendons were used as the control group. The expression of collagen type I was decreased, but type III was increased in TLHB. Disruption of elastic fibers was particularly observed in grade II specimens where the level of elastase-positive staining was significantly higher than in grade I specimens. Elastic fibers were not observed in the grade III area, implying a higher expression of elastase than in the grade I area. Results of Western blotting showed that the expression of elastin was higher in the control group and the levels of elastin significantly decreased in grades II and III of TLHB. Levels of osteopontin and elastase were increased in primary culture of human tenocytes after experiencing elastic derived peptide treatment. These results suggested that elastase may be caused by the disruption of elastic fibers in the development of chronic tendinopathy and that elastic derived peptide may enhance elastase and osteopontin expression. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1919-1926, 2017., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

A 73-year-old man presented with nontraumatic debilitating anterior left knee pain. Magnetic resonance imaging suggested a partial patellar tendon tear. However, ultrasound imaging revealed multiple small hyperechoic areas with posterior acoustic shadowing with intermixed hypoechoic fluid within the proximal patellar tendon, consistent with gouty tophi. The patient underwent ultrasound-guided needle barbotage of the tophi. Gout was confirmed by the presence of uric acid crystals in the aspirate. He had immediate pain relief. Ultrasound imaging 6 weeks later demonstrated healing of the tendon without tophi recurrence. At 6-month follow-up, the patient remained asymptomatic. This case highlights a rare cause of knee pain, promotes diagnostic ultrasound, and describes a novel treatment technique for intratendinous tophaceous gout., Level of Evidence: V., (Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Tendon is composed of fascicles bound together by the interfascicular matrix (IFM). Energy storing tendons are more elastic and extensible than positional tendons; behaviour provided by specialisation of the IFM to enable repeated interfascicular sliding and recoil. With ageing, the IFM becomes stiffer and less fatigue resistant, potentially explaining why older tendons become more injury-prone. Recent data indicates enrichment of elastin within the IFM, but this has yet to be quantified. We hypothesised that elastin is more prevalent in energy storing than positional tendons, and is mainly localised to the IFM. Further, we hypothesised that elastin becomes disorganised and fragmented, and decreases in amount with ageing, especially in energy storing tendons. Biochemical analyses and immunohistochemical techniques were used to determine elastin content and organisation, in young and old equine energy storing and positional tendons. Supporting the hypothesis, elastin localises to the IFM of energy storing tendons, reducing in quantity and becoming more disorganised with ageing. These changes may contribute to the increased injury risk in aged energy storing tendons. Full understanding of the processes leading to loss of elastin and its disorganisation with ageing may aid in the development of treatments to prevent age related tendinopathy.

Few studies discuss kinetic changes in tendinopathy models. We propose a customized corridor to evaluate dynamic weight bearing (DWB) and shearing forces. Sixty rats were randomly given ultrasound-assisted collagenase injections (Collagenase rats) or needle punctures (Control rats) in their left Achilles tendons, and then evaluated 1, 4, and 8 weeks later. The Collagenase rats always had significantly (p < 0.001) higher histopathological and ultrasound feature scores than did the Controls, significantly lower DWB values in the injured than in the right hindlimbs, and compensatorily higher (p < 0.05) DWB values in the contralateral than in the left forelimbs. The injured hindlimbs had lower outward shearing force 1 and 4 weeks later, and higher (p < 0.05) push-off shearing force 8 weeks later, than did the contralateral hindlimbs. Injured Control rat hindlimbs had lower DWB values than did the contralateral only at week 1. The Collagenase rats had only lower static weight bearing ratios (SWBRs) values than did the Controls at week 1 (p < 0.05). Our customized corridor showed changes in DWB compatible with histopathological and ultrasound feature changes in the rat tendinopathy model. The hindlimb SWBRs did not correspond with any tendinopathic changes.

Chronic tendinopathy is a frequent and disabling musculo-skeletal problem affecting the athletic and general populations. The affected tendon is presented with local tenderness, swelling, and pain which restrict the activity of the individual. Tendon degeneration reduces the mechanical strength and predisposes it to rupture. The pathogenic mechanisms of chronic tendinopathy are not fully understood and several major non-mutually exclusive hypotheses including activation of the hypoxia-apoptosis-pro-inflammatory cytokines cascade, neurovascular ingrowth, increased production of neuromediators, and erroneous stem cell differentiation have been proposed. Many intrinsic and extrinsic risk/causative factors can predispose to the development of tendinopathy. Among them, diabetes mellitus is an important risk/causative factor. This review aims to appraise the current literature on the epidemiology and pathology of tendinopathy in diabetic patients. Systematic reviews were done to summarize the literature on (a) the association between diabetes mellitus and tendinopathy/tendon tears, (b) the pathological changes in tendon under diabetic or hyperglycemic conditions, and (c) the effects of diabetes mellitus or hyperglycemia on the outcomes of tendon healing. The potential mechanisms of diabetes mellitus in causing and exacerbating tendinopathy with reference to the major non-mutually exclusive hypotheses of the pathogenic mechanisms of chronic tendinopathy as reported in the literature are also discussed. Potential strategies for the management of tendinopathy in diabetic patients are presented., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In tendon lesions, inflammation indicates the beginning of tissue repair and influences cell proliferation and the remodeling of the extracellular matrix (ECM). Low level laser (LLL) therapy has been an important method to induce tissue repair, and several studies have sought to better understand the therapeutic possibilities of this modality. This study analyzed the effect of LLL on the ECM of rat tendons during the early phase of the inflammatory process. Wistar rats received an intratendinous application of carrageenan adjacent to the osteotendinous region in the right paw. The animals were divided into the following groups: G1-intact, G2-animals with no treatment after the inflammation induction, G3-animals treated with LLL 1 and 3h after induction of inflammation (4J/cm 2 continuous). After 4h of application, the animals of the two groups were euthanized with isoflurane overdose. Our results demonstrate that LLL therapy can promote decrease in non-collagenous protein and glycosaminoglycans content, as well as an increase in metalloproteinases -9, which proved, for the first time, that LLL therapy promotes alterations in the inflamed tendons even when analyzed only four hours after this process occur and could be a useful tool to improve the balance in inflamed tissues., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To determine the association between bone marrow lesions (BMLs) and (teno)synovitis as assessed on magnetic resonance (MR) imaging in patients with pain in hand osteoarthritis (OA)., Methods: In 105 consecutive primary hand OA patients (83% women, mean age 59 years), who were diagnosed by rheumatologists and included in the HOSTAS (Hand OSTeoArthritis in Secondary care) cohort, contrast enhanced MR imaging of right distal and proximal interphalangeal joints were obtained. In 92 patients joint site specific pain upon palpation was assessed within 3 weeks of magnetic resonance imaging (MRI) examination. MR features were scored (0-3) following the Oslo hand OA score: BMLs, synovitis, cysts, flexor tenosynovitis (FTS). Additionally, extensor tendon inflammation (ETI) (0-3) was scored. Odds ratios (OR, 95% confidence interval (CI)) were calculated using generalized estimating equations for MR features with joint pain, adjusted for putative confounders. Stratified analyses were performed to investigate interaction., Results: BMLs, synovitis, cysts, FTS and ETI were demonstrated in 56%, 90%, 22%, 16% and 30% of patients, respectively. BMLs (grade 2/3 vs 0: 3.5 (1.6-7.7)) and synovitis (3 vs 0: OR 3.6 (95% CI 1.9-6.6)) were severity-dependent associated with joint pain, but FTS and ETI were not. Stratified analyses showed that BMLs did not associate with pain in the absence of synovitis, whereas synovitis was associated with pain in the absence of BMLs. Interaction was seen between BMLs and synovitis grade 2 or 3., Conclusion: In hand OA patients severe synovitis is associated with joint pain, which is worsened when BMLs co-occur, suggesting synovitis as primary target of treatment., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study was to analyse the relationship between long head of the biceps brachii (LHBT) lesions and subscapularis tears. The hypothesis was that a bicipital pulley might remain intact, even in the case of a subscapularis tear., Methods: Between 2010 and 2011, all patients who had a primary arthroscopic repair of a subscapularis tear were potentially included in this prospective study. The outcome of interest was the prevalence and type of arthroscopic lesions of the LHBT and bicipital pulley. Furthermore, the supposed pathomechanics of injury and the treatment proposed (conservative, pulley repair, tenodesis, tenotomy, etc.) was recorded. The following baseline characteristics were assessed: age, sex, shoulder side, and limb dominance., Results: Of the 218 patients, the superior glenohumeral ligament/coracohumeral ligament (SGHL/CHL) complex was normal in 54 patients (25%), stretched in 84 patients (39%), and absent in 77 patients (35%). Below the SGHL/CHL complex in the bicipital groove, the medial wall of the LHBT sheath was normal in 25%, partially torn in 39%, and completely torn in 35%. In 25 of the 218 patients (11%), a pathologic LHBT with an intact SGHL/CHL complex was observed. In these cases, the medial wall of the bicipital sheath was torn in 92%., Conclusions: The biceps pulley system, including the SGHL/CHL complex and subscapularis tendon, merits recognition as an important anatomical structure, and its lesions contribute to shoulder pathology. The subscapularis tendon is very important for the stability of the LHBT and should be included in the pulley system. In cases of a tear associated with a lesion of the SGHL/CHL complex, the LHBT is nearly always unstable and pathologic., Level of Evidence: II.

Peroneal tendon pathology is an important cause of lateral ankle pain and instability. Typical peroneal tendon disorders include tendinitis, tenosynovitis, partial and full thickness tendon tears, peroneal retinacular injuries, and tendon subluxations and dislocations. Surgery is usually indicated when conservative treatment fails. Familiarity with the peroneal tendon surgeries and expected postoperative imaging findings is essential for accurate assessment and to avoid diagnostic pitfalls. Cross-sectional imaging, especially ultrasound and MRI provide accurate pre-operative and post-operative evaluation of the peroneal tendon pathology. In this review article, the normal anatomy, clinical presentation, imaging features, pitfalls and commonly performed surgical treatments for peroneal tendon abnormalities will be reviewed. The role of dynamic ultrasound and kinematic MRI for the evaluation of peroneal tendons will be discussed. Normal and abnormal postsurgical imaging appearances will be illustrated., (Copyright © 2017 Elsevier B.V. All rights reserved.)

It was reported that substance P had beneficial effects in the healing of acute tendon injury. However, the relationship between substance P and degenerative tendinopathy development remains unclear. The purpose of this study was to determine the role of substance P in the pathogenesis of tendinopathy. Healthy and tendinopathy tendon were harvested from human and tenocytes were cultured individually. The expression levels of genes associated with tendinopathy were compared. Next, substance P was exogenously administered to the healthy tenocyte and the effect was evaluated. The results showed that tendinopathy tenocytes had higher levels of COL3A1 , MMP1 , COX2 , SCX , ACTA2 , and substance P gene expression compared to healthy tenocytes. Next, substance P treatment on the healthy tenocyte displayed similar changes to that of the tendinopathy tenocytes. These differences between the two groups were also determined by Western blot. Additionally, cells with substance P had the tendinopathy change morphologically although cellular proliferation was significantly higher compared to that of the control group. In conclusion, substance P enhanced cellular proliferation, but concomitantly increased immature collagen (type 3 collagen). Substance P plays a crucial role in tendinopathy development and could be a future therapeutic target for treatment., Competing Interests: The authors declare no conflict of interest.

Background: Adipose tissue is a promising source of mesenchymal stromal cells (MSCs) for the treatment of tendon disease. The goal of this study was to assess the effect of a single intralesional implantation of adipose tissue-derived mesenchymal stromal cells (AT-MSCs) on artificial lesions in equine superficial digital flexor tendons (SDFTs)., Methods: During this randomized, controlled, blinded experimental study, either autologous cultured AT-MSCs suspended in autologous inactivated serum (AT-MSC-serum) or autologous inactivated serum (serum) were injected intralesionally 2 weeks after surgical creation of centrally located SDFT lesions in both forelimbs of nine horses. Healing was assessed clinically and with ultrasound (standard B-mode and ultrasound tissue characterization) at regular intervals over 24 weeks. After euthanasia of the horses the SDFTs were examined histologically, biochemically and by means of biomechanical testing., Results: AT-MSC implantation did not substantially influence clinical and ultrasonographic parameters. Histology, biochemical and biomechanical characteristics of the repair tissue did not differ significantly between treatment modalities after 24 weeks. Compared with macroscopically normal tendon tissue, the content of the mature collagen crosslink hydroxylysylpyridinoline did not differ after AT-MSC-serum treatment (p = 0.074) while it was significantly lower (p = 0.027) in lesions treated with serum alone. Stress at failure (p = 0.048) and the modulus of elasticity (p = 0.001) were significantly lower after AT-MSC-serum treatment than in normal tendon tissue., Conclusions: The effect of a single intralesional injection of cultured AT-MSCs suspended in autologous inactivated serum was not superior to treatment of surgically created SDFT lesions with autologous inactivated serum alone in a surgical model of tendinopathy over an observation period of 22 weeks. AT-MSC treatment might have a positive influence on collagen crosslinking of remodelling scar tissue. Controlled long-term studies including naturally occurring tendinopathies are necessary to verify the effects of AT-MSCs on tendon disease.

Purpose: Accumulating clinical evidence indicates the risk of tendinopathy and spontaneous and/or simultaneous tendon ruptures associated with statin use. This experimental study was designed to evaluate and compare the biomechanical and histopathological effects of the three most commonly prescribed statins (simvastatin, atorvastatin and rosuvastatin) on the Achilles tendon in rats., Methods: Statins were administered by gavage to rats at daily doses of 20 and 40 mg/kg for 3 weeks. One week later, the Achilles tendons were dissected and their biomechanical properties, including ultimate tensile force, yield force and elastic modulus, were determined. The samples were stained with haematoxylin-eosin and examined under a light microscope. The biomechanical properties of the tibia were tested by three-point bending test. Bone mineral density (BMD) and the lengths of tibias were measured by computed tomography., Results: All the statins caused deterioration of the biomechanical parameters of the Achilles tendon. Histopathological analysis demonstrated foci of dystrophic calcification only in the statin-treated groups. However, the number and the total area of calcific deposits were similar between the statin groups. The biomechanical parameters of tibias were improved in all the statin groups. BMD in the statin-treated groups was not significantly different from the control group., Conclusion: All the statins tested are associated with calcific tendinopathy risk of which full awareness is required during everyday medical practice. However, statin-associated improvement of bone biomechanical properties is a favourable feature which may add to their beneficial effects in atherosclerotic cardiovascular disease, especially in the elderly.

We have used a murine Achilles tendinopathy model to investigate whether tissue changes (such as collagen disorganization, chondroid metaplasia, and loss of tensile properties) which are broadly characteristic of human tendinopathies, are accompanied by changes in the expression of chromatin-modifying enzymes and the methylation status of promoter regions of tendon cell DNA. Tendinopathy was induced by two intra-tendinous TGF-β1 injections followed by cage activity or treadmill running for up to 28 days. Activation of DNA methyltransferases occurred at 3 days after the TGF-β1 injections and also at 14 days, but only with treadmill activity. Genome-wide Methyl Mini-Seq™ analysis identified 19 genes with differentially methylated promoters, five of which perform functions with an apparent direct relevance to tendinopathy (Leprel2, Foxf1, Mmp25, Igfbp6, and Peg12). The functions of the genes identified included collagen fiber assembly and pericellular interactions, therefore their perturbation could play a role in the characteristic disorganization of fibers in affected tendons. We postulate that a study of the functional genomics of these genes in animal and human tendon could further delineate the pathogenesis of this multi-factorial complex disease. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:947-955, 2017., (© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objectives: To characterize abnormalities in the dorsal extensor tendons of the hand and determine the importance of these findings in rheumatoid arthritis., Methods: A retrospective cross-sectional study was done on 26 patients with rheumatoid arthritis who had sonography of their hands. B-mode and power Doppler joint activity were scored, and the extensor tendons were examined for B-mode changes and power Doppler signals. B-mode changes included anechoic fluid around tendons, hypoechoic tissue around tendons, paratendon tissue and tendon thickening, as well as vascularity around the tendon, for which peritendon power Doppler signals were recorded., Results: Forty-one hands and 205 joints were reviewed. Anechoic fluid around the tendons and peritendon power Doppler signals were observed in 41% and 39%, respectively; 44% and 28% of patients had B-mode and power Doppler scores in the upper tertile, respectively. For both B-mode and power Doppler scores, 3 categories or tertiles were created, 0 to 0.9, 1 to 1.9, and 2 to 3. We reported the percentage of patients with power Doppler and B-mode scores in this category. The severity of synovitis was associated with anechoic fluid around the tendons and peritendon power Doppler signals according to the Cochran-Mantel-Haenszel test. The common odds ratio was 3.52 (95% confidence interval, 1.45- 8.53) for anechoic fluid around the tendons and severe synovitis. The common odds ratio was 2.52 (95% confidence interval, 1.13-5.63) for peritendon power Doppler signals and severe synovitis., Conclusions: Findings at the dorsal extensor tendons were anechoic fluid around tendons, hypoechoic tissue around tendons, peritendon power Doppler signals, and tendon thickening. Patients with anechoic fluid and power Doppler signals were found to have more severe disease activity at the joints based on B-mode and power Doppler scores., (© 2017 by the American Institute of Ultrasound in Medicine.)

As social and health needs are changing, new challenges to develop innovative alternatives arise to address unmet medical needs. Personalized medicine is emerging as a promising and appealing therapeutic option. The use of patient's own plasma and platelets as therapeutics is providing new avenues in the treatment of acute and chronic tissue injuries by promoting tissue repair and regeneration. Plasma and platelet-based therapies mimic the physiological repair process by releasing autologous growth factors and creating a natural, biodegradable and transient scaffold that acts as transient matrix. This review summarizes the recent advances and challenges in the field of personalized plasma-based medicine and its potential to treat age-related diseases., (Copyright © 2016. Published by Elsevier B.V.)

The purposes of this case-control study (N = 20) were to examine the effects of insertional Achilles tendinopathy (IAT) and tendon region on tendon strain in patients with IAT compared to a control group without tendinopathy. An ultrasound transducer was positioned over the Achilles tendon insertion during dorsiflexion tasks, which included standing and partial squat. A non-rigid image registration-based algorithm was used to estimate transverse compressive and axial tensile strains of the tendon from radiofrequency ultrasound images, which was segmented into two regions (superficial tendon and deep). For transverse compressive strain, two-way mixed effects ANOVAs demonstrated that there were interaction effects between group and tendon region for both dorsiflexion tasks (Heel lowering, p = 0.004; Partial squat, p = 0.008). For axial tensile strain, the IAT group demonstrated a main effect of lower tensile strain than the control group (Standing, p = 0.001; Partial squat, p = 0.033). There was also a main effect of greater tensile strain in the superficial region of the tendon compared to the deep during standing (p = 0.002), but not during partial squat (p = 0.603). Reduced transverse compressive and axial tensile strains in the IAT group indicate altered mechanical properties specific to the region of IAT pathology. Additionally, patterns of compressive strain are consistent with the theory of calcaneal impingement contributing to IAT pathology. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:910-915, 2017., (© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Insertional Achilles tendinopathy and retrocalcaneal bursitis is difficult to treat, and several operative techniques have been used after failure of conservative management. Dorsal wedge calcaneal osteotomy has been described for the treatment of insertional Achilles pathology. It was hypothesized that dorsal wedge calcaneal osteotomy would be an effective and safe method for the treatment of athletes with insertional Achilles pathology unrelieved by nonoperative measures., Methods: Fifty-two athletes (64 feet) who had painful Achilles tendon syndrome unrelieved by 6 months of nonoperative measures were treated surgically. Dorsally based wedge calcaneal osteotomy was performed through a lateral approach, and 2 staples were used for fixation. Patients were scored pre- and postoperatively with the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot and Victorian Institute of Sports of Australia-Achilles (VISA-A) scores., Results: At a minimum follow-up of 3 years, the patients' AOFAS and VISA-A scores improved from 59.5 ± 15.0 and 65.9 ± 11.1 preoperatively to 95.7 ± 6.2 and 90.2 ± 8.4 postoperatively, respectively. Clinical results were considered excellent in 38 patients, good in 12 patients, and fair in 2 patients. Return to previous sports activity time was 21 (SD, 8.0) weeks. One patient necessitated a revision operation., Conclusion: Operative treatment of insertional Achilles pathology in athletes with dorsal closing wedge calcaneal osteotomy was a safe and effective method that allowed for a quicker return to previous level of sports activities compared with other techniques., Level of Evidence: Level IV, retrospective case series.

Objectives: The purpose of this study was to investigate and compare the serial changes of morphology and strain in the early process of Achilles tendinopathy in a rabbit model., Methods: A total of 10 New Zealand white rabbits underwent ligation of one of their Achilles tendons to induce ischemic injury. Both inflamed and contralateral Achilles tendons were serially evaluated with 3 follow-ups: the first on days 3 to 5, the second on days 9 to 13, and the third and last follow-up on days 15 to 20 after surgery. During each examination, tendon thickness was measured and red, green, and blue pixel intensities of the elastogram were analyzed using color histogram analysis software. Differences between the inflamed and control group were compared., Results: The mean thickness of the inflamed tendons increased during consecutive follow-ups and was significantly larger than that of control tendons (P < .01). The mean red pixel intensity ratio of the inflamed tendons was also serially increased and was higher than that in the control tendons, indicating softening. However, the difference was significant only in the second and third follow-ups (P < .01)., Conclusions: Tendon thickening and softening developed during the early process of Achilles tendinopathy in a rabbit model. Tendon softening may present later than thickening., (© 2017 by the American Institute of Ultrasound in Medicine.)

The term tendinopathy includes a series of pathologies, all of which have a combination of pain, swelling, and impaired performance. The terms tendinosis, tendinitis and peritendinitis are all within the main heading of tendinopathy; this terminology provides a more accurate understanding of the condition and highlights the uniformity of clinical findings while distinguishing the individual histopathological findings of each condition. Understanding the clinical features and the underlying histopathology leads to a more accurate clinical diagnosis and subsequent treatment selection. Misuse of the term tendinitis can lead to the underestimation of chronic degenerative nature of many tendinopathies, affecting the treatment selection., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Diabetes mellitus (DM) is associated with higher risk of tendinopathy, which reduces tolerance to exercise and functional activities and affects lifestyle and glycemic control. Expression of tendon-related genes and matrix metabolism in tenocytes are essential for maintaining physiological functions of tendon. However, the molecular mechanisms involved in diabetic tendinopathy remain unclear. We hypothesized that high glucose (HG) alters the characteristics of tenocyte. Using in vitro 2-week culture of tenocytes, we found that expression of tendon-related genes, including Egr1, Mkx, TGF-β1, Col1a2, and Bgn, was significantly decreased in HG culture and that higher glucose consumption occurred. Down-regulation of Egr1 by siRNA decreased Scx, Mkx, TGF-β1, Col1a1, Col1a2, and Bgn expression. Blocking AMPK activation with Compound C reduced the expression of Egr1, Scx, TGF-β1, Col1a1, Col1a2, and Bgn in the low glucose condition. In addition, histological examination of tendons from diabetic mice displayed larger interfibrillar space and uneven glycoprotein deposition. Thus, we concluded that high glucose alters tendon homeostasis through downregulation of the AMPK/Egr1 pathway and the expression of downstream tendon-related genes in tenocytes. The findings render a molecular basis of the mechanism of diabetic tendinopathy and may help develop preventive and therapeutic strategies for the pathology.

Introduction: local glucocorticoids injections are widely administered for the treatment of tendinopathies. positive results have been observed in some tendinopathies but not in others. moreover, worsening of symptoms, and even spontaneous tendon ruptures has been reported. the characteristics of the tendinopathies, the clinical peculiarities of the patient, and the technique used to administer glucocorticoids, can influence the therapeutic response. Areas covered: After reviewing the pertinent literature on the clinical results, basic information, both on the pathogenesis of tendinopathies and the effects of glucocorticoids on tendons, is reported. The pharmacological properties of glucocorticoids are useful to counteract some pathogenetic mechanisms of tendinopathies. However, several experimental studies suggest that the direct action of glucocorticoids on tendons is detrimental. Loss of collagen organization, impaired viability of fibroblasts, depletion of stem cells pool, and reduced mechanical properties have been observed. Expert opinion: Drawbacks of local glucocorticoids injections could be predicted on an individual basis, after a careful appraisal of patient characteristics and concomitant medications, along with the specific stage of tendon disease.

Objectives: Rotator cuff calcific tendinopathy (RCCT) with intraosseous extension is a rare complication of tendinous and peritendinous involvement. The purpose of our study is to evaluate the outcome of ultrasound-guided percutaneous irrigation of calcific tendinopathy (US-PICT) in patients with intraosseous involvement., Materials and Methods: From January 2011 to June 2014, patients with a clinical and imaging diagnosis of RCCT were prospectively categorised in two groups based on imaging findings: group A (10 patients) with intraosseous RCCT and group B (control group 35 patients) without osseous involvement. US-PICT followed by subacromial injection was applied to all patients in groups A and B. During a 1-year follow-up, treatment outcome in terms of pain and functional improvement was evaluated at 3 weeks, 3 months, 6 months, and 1 year, with the use of a four-grade scale. The study has been approved by our hospital's ethics committee., Results: Mean improvement scores of group A were significantly lower than those of group B at all time points (p < 0.0001). Improvement of group B was noted mainly within the first 3 months post-treatment (p = 0.016)., Conclusion: Outcomes of ultrasound-guided treatment in cases of RCCT with intraosseous extension are significantly less favourable than in purely tendinous or peritendinous disease.

Background: Growing evidence supports a key role for inflammation in the onset and progression of tendinopathy. However, the effect of the inflammatory infiltrate on tendon cells is poorly understood., Methods: We investigated stromal fibroblast activation signatures in tissues and cells from patients with tendinopathy. Diseased tendons were collected from well-phenotyped patient cohorts with supraspinatus tendinopathy before and after sub-acromial decompression treatment. Healthy tendons were collected from patients undergoing shoulder stabilisation or anterior cruciate ligament repair. Stromal fibroblast activation markers including podoplanin (PDPN), CD106 (VCAM-1) and CD248 were investigated by immunostaining, flow cytometry and RT-qPCR., Results: PDPN, CD248 and CD106 were increased in diseased compared to healthy tendon tissues. This stromal fibroblast activation signature persisted in tendon biopsies in patients at 2-4 years post treatment. PDPN, CD248 and CD106 were increased in diseased compared to healthy tendon cells. IL-1β treatment induced PDPN and CD106 but not CD248. IL-1β treatment induced NF-κB target genes in healthy cells, which gradually declined following replacement with cytokine-free medium, whilst PDPN and CD106 remained above pre-stimulated levels. IL-1β-treated diseased cells had more profound induction of PDPN and CD106 and sustained expression of IL6 and IL8 mRNA compared to IL-1β-treated healthy cells., Conclusions: We conclude that stromal fibroblast activation markers are increased and persist in diseased compared to healthy tendon tissues and cells. Diseased tendon cells have distinct stromal fibroblast populations. IL-1β treatment induced persistent stromal fibroblast activation which was more profound in diseased cells. Persistent stromal fibroblast activation may be implicated in the development of chronic inflammation and recurrent tendinopathy. Targeting this stromal fibroblast activation signature is a potential therapeutic strategy.

Although of several studies that associate chronic hyperglycemia with tendinopathy, the connection between morphometric changes as witnessed by magnetic resonance (MR) images, nanostructural changes, and inflammatory markers have not yet been fully established. Therefore, the present study has as a hypothesis that the Achilles tendons of rats with diabetes mellitus (DM) exhibit structural changes. The animals were randomly divided into two experimental groups: Control Group (n = 06) injected with a vehicle (sodium citrate buffer solution) and Diabetic Group (n = 06) consisting of rats submitted to intraperitoneal administration of streptozotocin. MR was performed 24 days after the induction of diabetes and images were used for morphometry using ImageJ software. Morphology of the collagen fibers within tendons was examined using Atomic Force microscopy (AFM). An increase in the dimension of the coronal plane area was observed in the diabetic group (8.583 ± 0.646 mm2/100g) when compared to the control group (4.823 ± 0.267 mm2/100g) resulting in a significant difference (p = 0.003) upon evaluating the Achilles tendons. Similarly, our analysis found an increase in the size of the transverse section area in the diabetic group (1.328 ± 0.103 mm2/100g) in comparison to the control group (0.940 ± 0.01 mm2/100g) p = 0.021. The tendons of the diabetic group showed great irregularity in fiber bundles, including modified grain direction and jagged junctions and deformities in the form of collagen fibrils bulges. Despite the morphological changes observed in the Achilles tendon of diabetic animals, IL1 and TNF-α did not change. Our results suggest that DM promotes changes to the Achilles tendon with important structural modifications as seen by MR and AFM, excluding major inflammatory changes., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Diabetes mellitus is one of the most common metabolic problems and is characterized by persistent hyperglycaemia. Exposure to chronic hyperglycaemia can affect many tissues including the Achilles Tendon, which is one of the largest tendons in the body. The current literature on the effects of hyperglycaemia on tendons is sparse, though evidence on rat models does suggest a process of chronic degeneration, which is increased in the presence of neuropathy and deformity. There is no epidemiological data on rupture of Achilles tendon in diabetes. Similarly, the knowledge of the best treatments for this condition in people with diabetes is also lacking., Conclusion: In this review we have systematically analysed current literature in this area and suggested future studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)