Study of the Synergistic Immunomodulatory and Antifibrotic Effects of Dual-Loaded Budesonide and Serpine1 siRNA Lipid-Polymer Nanoparticles Targeting Macrophage Dysregulation in Tendinopathy.

Musculoskeletal diseases involving tissue injury comprise tendon, ligament, and muscle injury. Recently, macrophages have been identified as key players in the tendon repair process, but no therapeutic strategy involving dual drug delivery and gene delivery to macrophages has been developed for targeting the two main dysregulated aspects of macrophages in tendinopathy, i.e., inflammation and fibrosis. Herein, the anti-inflammatory and antifibrotic effects of dual-loaded budesonide and serpine1 siRNA lipid-polymer hybrid nanoparticles (LPNs) are evaluated in murine and human macrophage cells. The modulation of the gene and protein expression of factors associated with inflammation and fibrosis in tendinopathy is demonstrated by real time polymerase chain reaction and Western blot. Macrophage polarization to the M2 phenotype and a decrease in the production of pro-inflammatory cytokines are confirmed in macrophage cell lines and primary cells. The increase in the activity of a matrix metalloproteinase involved in tissue remodelling is proven, and studies evaluating the interactions of LPNs with T cells proved that dual-loaded LPNs act specifically on macrophages and do not induce any collateral effects on T cells. Overall, these dual-loaded LPNs are a promising combinatorial therapeutic strategy with immunomodulatory and antifibrotic effects in dysregulated macrophages in the context of tendinopathy.

Establishment of a Mouse Degenerative Model of Patellar Tendinopathy with Upregulation of Inflammation.

There is no mouse model of patellar tendinopathy. This study aimed to establish a mouse inflammatory and degenerative patellar tendon injury model, which will facilitate research on patellar tendinopathy using advanced molecular tools including transgenic models. Collagenase at different doses (low dose (LD), medium dose (MD), high dose (HD)) or saline was injected over the mouse patellar tendon. At weeks 1, 2, 4, and 8 post-injection, the tendons were harvested for histology and further examined by micro-computed tomography (microCT) imaging at week 8. The optimal dose group and the saline group were further evaluated by immunohistochemical staining, gait pattern, and biomechanical properties. The histopathological score increased dose-dependently post-collagenase injection. Ectopic mineralization was observed and increased with collagenase dose. The LD group was selected for further analysis. The expression of IL-10, TNF-α, and MMP-1 significantly increased post-injection. The changes of limb idleness index (ΔLII) compared to preinjury state were significantly higher, while the ultimate load, stiffness, ultimate stress, and maximum Young's modulus were significantly lower in the LD group compared to the saline group. A mouse inflammatory degenerative model of patellar tendon injury resembling tendinopathy was established as indicated by the dose-dependent increase in tendon histopathology, ectopic calcification, decrease in biomechanical properties, and pain-associated gait changes.

Therapeutic exercises in the clinical practice of Brazilian physical therapists in the management of rotator cuff tendinopathy: An online survey.

The objective of this study was to investigate how Brazilian physical therapists (PTs) use therapeutic exercises in the rehabilitation of individuals with rotator cuff (RC) tendinopathy. The study used an online survey with a mix of 62 open- and closed-ended questions divided into three sections: participant demographics, professional experience, and clinical practice in the rehabilitation of patients with RC tendinopathy. One hundred and fifty-nine Brazilian physical therapists completed the survey. Most of our sample recommended isometric exercises (69.9%) in the initial phase of rehabilitation and eccentric exercises (47.4%) in the advanced phase. However, there was a wide variability in determining the volume of exercises, particularly with isometric exercises. Most of our sample considered patient comfort and pain levels when adjusting exercise intensity, regardless of exercise type. The majority (48.40%) recommended weekly reassessment and modification of exercises. Additionally, despite pain being a key factor for discharge and the primary adverse effect of exercise, most of our sample would not discontinue exercises in case of pain during the early and late phases of rehabilitation. Despite the lack of consensus on some aspects, the clinical practice of our sample is in line with the current literature and practice in other countries. However, further research and implementation are crucial to enhance future rehabilitation outcomes, including exploring the exercise training volume, the safety and effectiveness of exercising with pain and identifying the optimal pain level for best results.

A pilot study exploring the use of hyaluronic acid in treating insertional achilles tendinopathy.

PURPOSE: This study explores the use of ultrasound-guided Hyaluronic Acid (HA) injections for Insertional Achilles Tendinopathy (IAT). METHODS: A cohort of 15 ankles diagnosed with IAT received three weekly ultrasound-guided HA injections. The Victorian Institute of Sport Assessment - Achilles (VISA-A) questionnaire scored the severity of symptoms and functional impairment before treatment, and at one and six months post-treatment. RESULTS: Significant improvement was observed in VISA-A scores post-treatment, rising from an average baseline of 34.8 ± 15.2 (11-63) to 53.6 ± 20.9 (15-77) after one month, and then to 50.7 ± 18.6 (20-75) after six months. No adverse reactions were noted, underscoring the safety of the intervention. CONCLUSION: The pilot study presents HA injections as a potentially effective treatment for IAT, while interpretation of these findings must take into account the variability in results, indicating a range of patient responses. It encourages further research to confirm these findings and to explore HA's full potential in managing IAT, despite the limitations of a small sample size and lack of control group.

Diagnostic utility of shear wave elastography in musculoskeletal injuries: A narrative review.

Shear wave elastography (SWE) is an emerging and promising ultrasound modality, and is more recently employed in the diagnosis of musculoskeletal (MSK) pathologies. SWE evaluates tissue stiffness by measuring the speed of propagating acoustic waves through body tissue structures. Knowing the variations in stiffness of MSK soft tissue can provide helpful diagnostic insight for the evaluation of pathology in muscles, tendons, ligaments, nerves, and other soft tissues. The goal of this review is to synthesize recent literature on the utility of SWE for MSK pathology diagnosis. This review reveals that SWE adds important diagnostic data for the evaluation of several pathologies, such as median mononeuropathy at the wrist, Achilles tendinopathy, and plantar fasciitis. The review also reveals a lack of evidence pertaining to appropriate standardization of use and the connection to reliable and valid diagnostic benefit in the clinical setting.

Arthroscopic Surgery Versus Nonoperative Treatment for Calcific Tendinitis of the Shoulder: A Retrospective Cohort Study.

BACKGROUND: Treatment options for calcific tendinitis (CT) of the shoulder remain controversial. A consensus for an operative indication for this condition is lacking. PURPOSE: To compare nonoperative versus operative treatment for shoulder CT and analyze factors affecting the prognosis after treatment. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 180 patients diagnosed with symptomatic CT between January 2017 and September 2021 were evaluated in this retrospective cohort study. There were 103 patients treated nonoperatively at our institution, which included the use of nonsteroidal anti-inflammatory drugs, acupuncture, steroid injections, extracorporeal shock wave therapy, and ultrasound-guided needle aspiration/percutaneous irrigation. However, 77 patients were treated with arthroscopic surgery after 6 months of failed nonoperative treatment. The visual analog scale (VAS) for pain, the Constant-Murley score, and imaging were used to assess and evaluate outcomes. Descriptive data, functional outcomes, and imaging findings were compared between the operative and nonoperative groups before and after propensity score matching. Additionally, prognostic factors including calcium deposit size, tendon infiltration by calcium deposits, involvement of single or multiple tendons, and occurrence of rotator cuff tears were analyzed by comparing the groups to determine their effect on treatment options and recovery. RESULTS: Magnetic resonance imaging showed that the supraspinatus tendon (66.7%) was most commonly involved, followed by the infraspinatus (42.8%) and subscapularis (21.1%) tendons. Tendon infiltration by calcium deposits was observed in 84.4% of the patients, and rotator cuff tears occurred in 30.0% of the patients. After propensity score matching, there was no significant difference in changes in the Constant-Murley score (48.1 ± 25.4 vs 49.0 ± 22.8, respectively; P = .950) and VAS score (4.9 ± 2.3 vs 4.5 ± 1.9, respectively; P = .860) between the operative and nonoperative groups at the final follow-up. However, for patients with shoulder CT and without rotator cuff tears, there was a significant difference in changes in the Constant-Murley score (52.93 ± 25.18 vs 42.13 ± 22.35, respectively; P = .012) and VAS score (5.21 ± 2.06 vs 3.81 ± 1.98, respectively; P < .001) between the operative and nonoperative groups, but the recovery time in the operative group was longer than that in the nonoperative group (86.92 ± 138.56 vs 30.42 ± 54.97 days, respectively; P = .016). The results also showed that calcium deposit size, involvement of multiple tendons, and tendon infiltration by calcium deposits did not affect the recovery time after treatment. The survival analysis showed that rotator cuff tears affected the complete recovery of shoulder function. CONCLUSION: This study demonstrated no significant difference between nonoperative and operative treatment for patients with shoulder CT, on the whole. However, for patients with shoulder CT and without rotator cuff tears, the effect of operative treatment was better than that of nonoperative treatment; yet, operative treatment was shown to prolong the recovery time. Calcium deposit size, tendon infiltration by calcium deposits, and involvement of multiple tendons did not correlate with recovery time or the recovery of function. A rotator cuff tear was the only factor affecting the complete recovery of shoulder function.

Satisfactory mid-term clinical outcomes of endoscopic tenotomy for iliopsoas tendinopathy following total hip arthroplasty.

PURPOSE: To report 5-year outcomes of endoscopic iliopsoas tenotomy in patients with iliopsoas tendinopathy following total hip arthroplasty (THA) and determine whether clinical scores are associated with cup position. METHODS: Patients who underwent endoscopic iliopsoas tenotomy for iliopsoas tendinopathy following THA (2014-2017) were contacted. Indications for endoscopic iliopsoas tenotomy after THA were groin pain during active hip flexion, exclusion of other causes of groin pain, and no pain relief after 6 months of conservative treatment. Pretenotomy cup inclination and anteversion were measured on radiographs; axial and sagittal cup overhang were measured on computed tomography (CT) scans. Oxford hip score (OHS), modified Harris hip score (mHHS), and groin pain were assessed. RESULTS: The initial cohort comprised 16 men (17 hips) and 31 women (32 hips), aged 60.7 ± 10.6 years. Cup inclination and anteversion were, respectively, 46.2 ± 6.2° and 14.6 ± 8.4°, while axial and sagittal cup overhang were, respectively, 4.4 ± 4.0 mm and 6.9 ± 4.5 mm. At ≥5 years follow-up, four hips underwent cup and stem revision, two underwent isolated cup revision and one underwent secondary iliopsoas tenotomy. OHS improved by 23 ± 10 and mHHS improved by 31 ± 16. Posttenotomy groin pain was slight in 20.0%, mild in 17.5% and moderate in 12.5%. Regression analyses revealed that net change in mHHS decreased with sagittal cup overhang (ß = -3.1; 95% confidence interval [CI] = -4.6 to -1.7; p < 0.001), but that there were no associations between cup position and net change in OHS. CONCLUSIONS: Endoscopic iliopsoas tenotomy provides good mid-term clinical outcomes in patients with iliopsoas tendinopathy following THA. Furthermore, improvements in mHHS were found to decrease with increasing sagittal cup overhang, in cases for which adequate preoperative imaging was available. LEVEL OF EVIDENCE: Level IV.

Weights, resistance bands, and rest days are best for tendinopathy.

The studyPavlova AV, Shim JSC, Moss R, et al. Effect of resistance exercise dose components for tendinopathy management: a systematic review with meta-analysis. Br J Sports Med 2023;57:1327-34.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/weights-resistance-bands-rest-days-best-tendinopathy/.

Needle­based gastrocnemius lengthening: a novel ultrasound­guided noninvasive technique: part II-clinical results.

BACKGROUND: Isolated gastrocnemius contracture has been associated with more than 30 lower limb disorders, including plantar heel pain/plantar fasciitis, Achilles tendinosis, equinus foot, adult flatfoot, and metatarsalgia. Although many techniques are available for gastrocnemius recession, potential anesthetic, cosmetic, and wound-related complications can lead to patient dissatisfaction. Open and endoscopic recession techniques usually require epidural or general anesthesia, exsanguination of the lower extremities and stitches and can damage the sural nerve, which is not under the complete control of the surgeon at all stages of the procedure. The purpose of this study is to evaluate the clinical results of a surgical technique for gastrocnemius lengthening with a needle, as previously described in cadaver specimens. METHODS AND RESULTS: We performed a prospective study of ultrasound-guided gastrocnemius tendon lengthening in level II using a needle in 24 cases (19 patients) of gastrocnemius contracture. The study population comprised 12 males and 7 females. Mean age was 41 years (18-64). All but 5 recessions were bilateral and occurred simultaneously. The indication for the procedure was gastrocnemius contracture; although the patients also presented other conditions such as non-insertional Achilles tendinopathy in 6 patients (2 were bilateral), insertional Achilles calcifying enthesitis in 4 (1 was bilateral), metatarsalgia in 4, flexible flat foot in 1 and plantar fasciitis in 5 (2 were bilateral). The inclusion criteria were the failure of a previous conservative protocol, that the Silfverskiöld test was positive, and that the pathology suffered by the patient was within the indications for surgical lengthening of the patients and were described in the scientific literature. The exclusion criteria were that the inclusion criteria were not met, and patients with surgical risk ASA 3 or more and children. In these patients, although possible, it is preferable to perform the procedure in the operating room with monitoring, as well as in children since they could be agitated during the procedure at the office. We used the beveled tip of an Abbocath needle as a surgical scalpel. All patients underwent recession of the gastrocnemius tendon, as in an incomplete Strayer release. We evaluated pre- and postoperative dorsiflexion, outcomes, and procedural pain (based on a visual analog scale and the American Orthopedic Foot and Ankle Society scores), as well as potential complications. No damage was done to the sural bundle. RESULTS: Ankle dorsiflexion increased on average by 17.89°. The average postoperative visual analog score for pain before surgery was 5.78, 5.53 in the first week, 1.89 at 1 month, and 0.26 at 3 months, decreasing to 0.11 at 9 months. The mean postoperative American Orthopedic Foot and Ankle Society Ankle-Hindfoot score the average was 50.52 before surgery, 43.42 at 1 week, 72.37 at 1 month, 87.37 at 3 months, and 90.79 at 9 months. CONCLUSION: Ultrasound-guided needle lengthening of the gastrocnemius tendon is a novel, safe, and effective technique that enables the surgeon to check all the structures clearly, thus minimizing the risk of neurovascular damage. The results are encouraging, and the advantages of this approach include absence of a wound and no need for stitches. Recovery is fast and relatively painless. A specific advantage of ultrasound-guided needle lengthening of the gastrocnemius tendon is the fact that it can be performed in a specialist's office, with a very basic instrument set and local anesthesia, thus reducing expenses.

Strength and Functional Outcomes Following Achilles Tendon Reconstruction With Hamstring Tendon Autograft Augmentation.

BACKGROUND: The proposed advantages of hamstring autograft reconstruction when compared to alternative procedures, such as flexor hallucis longus (FHL) transfer, V-Y lengthening, and allograft reconstruction, are improved healing and reproduction of normal tendon biomechanics and reduced morbidity within the foot and ankle. In this study, we examined the effect of Achilles tendon reconstruction using hamstring autografts on strength and functional outcomes. METHODS: Patients who underwent Achilles repair with a hamstring autograft for insertional or midsubstance tendinopathy, delayed diagnosis of rupture, or infection after primary repair were evaluated for inclusion. Forty-six patients were identified; 12 further augmented with an FHL transfer are included in the analysis. Isokinetic testing was completed with a Biodex dynamometer under supervision of a physical therapist masked to surgical side. Pre- and postoperative Foot and Ankle Outcome Scores (FAOS, before March 2016) or Patient-Reported Outcomes Measurement Information System (PROMIS, after March 2016) surveys were collected. RESULTS: For knee flexion, peak torque was not significantly different when comparing operative and nonoperative sides at 180 degrees/second (45.38 Nm vs 45.96 Nm; P = .69) nor at 300 degrees/second (44.2 Nm vs 47.02 Nm; P = .069). Knee extension absolute peak torque was only found to be significantly weaker on the operative side at the faster testing (75.5 Nm vs 79.56 Nm; P < .05). Peak ankle plantarflexion torque was significantly weaker on the operative side at both the slower speed (60 degrees/second: 39.9 Nm vs 48.76 Nm; P < .005) and the faster speed (120 degrees/second: 31.3 Nm vs 40.7 Nm; P < .001). Average power for ankle plantarflexion did not differ significantly from the operative side to the nonoperative side in the slower test (26.46 W vs 27.48 W; P = .60) but did significantly differ on the faster test (32.13 W vs 37.63 W; P = .041). At an average of 19.9 months postoperation, all physical function and pain-related patient-reported outcome scores showed clinically and statistically significant improvement. CONCLUSION: Achilles reconstruction with a hamstring autograft ± FHL transfer allowed patients with severe Achilles pathology to return to good subjective function, with modest deficits in calf strength compared with the uninjured side. Overall knee flexion strength did not appear impaired. These results suggest that hamstring autograft reconstruction is a viable method to treat these complex cases involving a lack of healthy tissue, allowing patients to return to symptom-free physical function and athletic activity. LEVEL OF EVIDENCE: Level IV, case series.

The Heel Complex: Anatomy, Imaging, Pathologic Conditions, and Treatment.

The differential diagnosis for heel pain is broad but primarily involves abnormalities of the Achilles tendon, calcaneus, and plantar fascia. Achilles tendon disorders include tendinosis, tendinitis, and partial or complete tears. Tendinosis refers to tendon degeneration, while tendinitis is inflammation after acute overload. Untreated tendinosis can progress to partial or complete tears. Tendon disorders can be accompanied by paratenonitis or inflammation of the loose sheath enclosing the tendon. Initial management involves rehabilitation and image-guided procedures. Operative management is reserved for tendon tears and includes direct repair, tendon transfer, and graft reconstruction. The calcaneus is the most commonly fractured tarsal bone. The majority of fractures are intra-articular; extra-articular fractures, stress or insufficiency fractures, medial process avulsion, and neuropathic avulsion can also occur. Posterosuperior calcaneal exostosis or Haglund deformity, retrocalcaneal bursitis, and insertional Achilles tendinosis form the characteristic triad of Haglund syndrome. It is initially managed with orthotics and physiotherapy. Operative management aims to correct osseous or soft-tissue derangements. The plantar fascia is a strong fibrous tissue that invests the sole of the foot and contributes to midfoot stability. Inflammation or plantar fasciitis is the most common cause of heel pain and can be related to overuse or mechanical causes. Acute rupture is less common but can occur in preexisting plantar fasciitis. Conservative treatment includes footwear modification, calf stretches, and percutaneous procedures. The main operative treatment is plantar fasciotomy. Plantar fibromatosis is a benign fibroblastic proliferation within the fascia that can be locally aggressive and is prone to recurrence. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Can imaging determine if a rotator cuff tear is traumatic?

AIM: We reviewed the last decade of literature to update a previous publication on this topic by the senior author. In New Zealand, traumatic causation has implications for entitlement for treatment though the Accident Compensation Corporation (ACC). Acuity and chronicity may also be relevant in determining repairability. METHODS: Literature was reviewed regarding acromial morphology, greater tuberosity (GT) cysts, acromiohumeral interval (AHI), fatty degeneration and atrophy, acromioclavicular (AC) arthrosis, tendinopathy, bursal changes and other features. RESULTS: Some factors can be considered normal for those middle aged and older, including AC arthrosis, type 1 and 2 acromion and tendinopathy. Some factors may indicate acuity, including haemorrhage and debris, GT oedema, mid-substance soft tissue tear, kinking of the tendon and isolated complete subscapularis tears. Other factors may be associated with chronicity, including significant fatty degeneration, positive tangent sign for atrophy, anterior GT cysts, type 3 acromion, critical shoulder angle (CSA) >35 degrees and acromial index (AI) <0.7. CONCLUSION: A multitude of factors on imaging may infer, to a varying degree, the likelihood of acuity or chronicity. The patient history is also of importance in determining causation.

A Passive Ankle Dorsiflexion Testing System for an In Vivo Model of Overuse-induced Tendinopathy.

Tendinopathy is a chronic tendon condition that results in pain and loss of function and is caused by repeated overload of the tendon and limited recovery time. This protocol describes a testing system that cyclically applies mechanical loads via passive dorsiflexion to the rat Achilles tendon. The custom-written code consists of pre- and post-cyclic loading measurements to assess the effects of the loading protocol along with the feedback control-based cyclic fatigue loading regimen. We used 25 Sprague-Dawley rats for this study, with 5 rats per group receiving either 500, 1,000, 2,000, 3,600, or 7,200 cycles of fatigue loads. The percentage differences between the pre- and post-cyclic loading measurements of the hysteresis, peak stress, and loading and unloading moduli were calculated. The results demonstrate that the system can induce varying degrees of damage to the Achilles tendon based on the number of loads applied. This system offers an innovative approach to apply quantified and physiological varying degrees of cyclic loads to the Achilles tendon for an in vivo model of fatigue-induced overuse tendon injury.

Exploring the feasibility and acceptance of an optimised physiotherapy approach for lateral elbow tendinopathy: a qualitative investigation within the OPTimisE trial.

OBJECTIVES: To explore the acceptability of an optimised physiotherapy (OPTimisE) intervention for people with lateral elbow tendinopathy (LET) and feasibility of comparing it to usual care in a randomised controlled trial. DESIGN: Semistructured interviews, analysed using thematic analysis and mapped onto the COM-B model of behaviour change. SETTING: Conducted as part of the OPTimisE Pilot & Feasibility randomised controlled trial within physiotherapy departments in the United Kingdom National Health Service. PARTICIPANTS: 17 patients with LET (purposively sampled to provide representativeness based on age, sex, ethnicity, deprivation index and treatment allocation) and all 8 physiotherapists involved as treating clinicians or site principal investigators. RESULTS: Four themes were identified. First, participants reported the OPTimisE intervention as acceptable. Second, differences between the OPTimisE intervention and usual care were identified, including the use of an orthosis, holistic advice/education including modifiable risk factors, forearm stretches, general upper body strengthening and a more prescriptive exercise-dosing regimen. Third, participants provided feedback related to the trial resources, which were viewed positively, but identified language translation as a need. Fourth, feedback related to trial processes identified the need for changes to outcome collection and reduction of administrative burden. From the perspective of adopting the OPTimisE intervention, we found evidence that participants were able to change their behaviour. Considering the findings through the lens of the COM-B model, the intervention is likely to be deliverable in practice and the trial can be delivered at scale with some additional support for physiotherapists. CONCLUSIONS: Overall, the OPTimisE intervention was found to be different to usual care and acceptable to patients and physiotherapists. The study highlighted the need to refine trial processes and resources prior to a full-scale trial, to reduce administrative burden, increase support for physiotherapists, improve return rate of outcome questionnaires and provide language translation. TRIAL REGISTRATION NUMBER: ISRCTN database 19 July 2021. https://www.isrctn.com/ISRCTN64444585.

To allow or avoid pain during shoulder rehabilitation exercises for patients with chronic rotator cuff tendinopathy-Study protocol for a randomized controlled trial (the PASE trial).

BACKGROUND: Rotator cuff (RC) tendinopathy is the most reported shoulder disorder in the general population with highest prevalence in overhead athletes and adult working-age population. A growing body of evidence support exercise therapy as an effective intervention, but to date there are no prospective randomized controlled trials addressing pain as an intervention variable. METHODS: A single-site, prospective, pragmatic, assessor-blinded randomized controlled superiority trial. Eighty-four patients aged 18-55 years with chronic (symptom duration over 3 months) RC tendinopathy are randomized 1:1 to receive shoulder exercise during which pain is either allowed or avoided. The intervention period lasts 26 weeks. During that period, participants in both groups are offered 8 individual on-site sessions with an assigned sports physiotherapist. Participants perform home exercises and are provided with a pain and exercise logbook and asked to report completed home-based exercise sessions and reasons for not completing sessions (pain or other reasons). Patients are also asked to report load and the number of sets and repetitions per sets for each exercise session. The logbooks are collected continuously throughout the intervention period. The primary and secondary outcomes are obtained at baseline, 6 weeks, 26 weeks, and 1 year after baseline. The primary outcome is patient-reported pain and disability using the Shoulder PAin and Disability Index (SPADI). Secondary outcomes are patient-reported pain and disability using Disability Arm Shoulder and Hand short-form (Quick DASH), and shoulder pain using Numeric Pain Rating Scale. Objective outcomes are shoulder range of motion, isometric shoulder muscle strength, pain sensitivity, working ability, and structural changes in the supraspinatus tendon and muscle using ultrasound. DISCUSSION: The results of this study will contribute knowledge about the treatment strategies for patients with RC tendinopathy and help physiotherapists in clinical decision-making. This is the first randomized controlled trial comparing the effects of allowing pain versus avoiding pain during shoulder exercises in patients with chronic RC tendinopathy. If tolerating pain during and after exercise proves to be effective, it will potentially expand our understanding of "exercising into pain" for this patient group, as there is currently no consensus. TRIAL REGISTRATION: ClinicalTrials.gov NCT05124769. Registered on August 11, 2021.

MicroRNA-146a gene transfer ameliorates senescence and senescence-associated secretory phenotypes in tendinopathic tenocytes.

OBJECTIVE: Tendinopathy is influenced by multiple factors, including chronic inflammation and aging. Senescent cells exhibit characteristics such as the secretion of matrix-degrading enzymes and pro-inflammatory cytokines, collectively known as senescence-associated secretory phenotypes (SASPs). Many of these SASP cytokines and enzymes are implicated in the pathogenesis of tendinopathy. MicroRNA-146a (miR-146a) blocks senescence by targeting interleukin-1ß (IL-1ß) receptor-associated kinase 4 (IRAK-4) and TNF receptor-associated factor 6 (TRAF6), thus inhibiting NF-κB activity. The aims of this study were to (1) investigate miR-146a expression in tendinopathic tendons and (2) evaluate the role of miR-146a in countering senescence and SASPs in tendinopathic tenocytes. METHODS: MiR-146a expression was assessed in human long head biceps (LHB) and rat tendinopathic tendons by in situ hybridization. MiR-146a over-expression in rat primary tendinopathic tenocytes was achieved by lentiviral vector-mediated precursor miR-146a transfer (LVmiR-146a). Expression of various senescence-related markers was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunoblotting and immunofluorescence. MiR-146a expression showed a negative correlation with the severity of tendinopathy in human and rat tendinopathic tendons (p<0.001). RESULTS: Tendinopathic tenocyte transfectants overexpressing miR-146a exhibited downregulation of various senescence and SASP markers, as well as the target molecules IRAK-4 and TRAF6, and the inflammatory mediator phospho-NF-κB. Additionally, these cells showed enhanced nuclear staining of high mobility group box 1 (HMGB1) compared to LVmiR-scramble-transduced controls in response to IL-1ß stimulation. CONCLUSIONS: We demonstrate that miR-146a expression is negatively correlated with the progression of tendinopathy. Moreover, its overexpression protects tendinopathic tenocytes from SASPs and senescence through the IRAK-4/TRAF6/NF-kB pathway.

Early delivery of human umbilical cord mesenchymal stem cells improves healing in a rat model of Achilles tendinopathy.

Objective: This study aimed to explore the efficacy and optimal delivery time of human umbilical cord mesenchymal stem cells (hUC-MSCs) in treating collagenase-induced Achilles tendinopathy. Methods: Achilles tendinopathy in rats at early or advanced stages was induced by injecting collagenase I into bilateral Achilles tendons. A total of 28 injured rats were injected with a hUC-MSC solution or normal saline into bilateral tendons twice and sampled after 4 weeks for histological staining, gene expression analysis, transmission electron microscope assay and biomechanical testing analysis. Results: The results revealed better histological performance and a larger collagen fiber diameter in the MSC group. mRNA expression of TNF-α, IL-1ß and MMP-3 was lower after MSC transplantation. Early MSC delivery promoted collagen I and TIMP-3 synthesis, and strengthened tendon toughness. Conclusion: hUC-MSCs demonstrated a therapeutic effect in treating collagenase-induced Achilles tendinopathy, particularly in the early stage of tendinopathy.

The Use of Shear-Wave Ultrasound Elastography in the Diagnosis and Monitoring of Musculoskeletal Injuries.

Ultrasound elastography is a valuable method employed to evaluate tissue stiffness, with shear-wave elastography (SWE) recently gaining significance in various settings. This literature review aims to explore the potential of SWE as a diagnostic and monitoring tool for musculoskeletal injuries. In total, 15 studies were found and included in the review. The outcomes of these studies demonstrate the effectiveness of SWE in detecting stiffness changes in individuals diagnosed with Achilles tendinopathy, Achilles tendon rupture, rotator cuff rupture, tendinosis of the long head of the biceps tendon, injury of the supraspinatus muscle, medial tibial stress syndrome, and patellar tendinopathy. Moreover, SWE proves its efficacy in distinguishing variations in tissue stiffness before the commencement and after the completion of rehabilitation in cases of Achilles tendon rupture and patellar tendinopathy. In summary, the findings from this review suggest that SWE holds promise as a viable tool for diagnosing and monitoring specific musculoskeletal injuries. However, while the field of ultrasound elastography for assessing musculoskeletal injuries has made considerable progress, further research is imperative to corroborate these findings in the future.