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.

Evaluation of Anti-Nociceptive, Anti-Inflammatory, and Anti-Fibrotic effects of noscapine against a rat model of Achilles tendinopathy.

During tendinopathy, prolonged inflammation results in fibrosis and the adherence of tendons to the adjacent tissues, causing discomfort and movement disorders. As a natural compound, noscapine has several anti-inflammatory and anti-fibrotic properties. Therefore, we aimed to investigate the effects of noscapine against a rat model of tendinopathy. We created a surgical rat model of Achilles tendon damage to emulate tendinopathy. Briefly, an incision was made on the Achilles tendon, and it was then sutured using an absorbable surgical thread. Immediately, the injured area was topically treated with the vehicle, noscapine (0.2, 0.6, and 1.8 mg/kg), or dexamethasone (0.1 mg/kg) as a positive control. During the 19-day follow-up period, animals were assessed for weight, behavior, pain, and motor coordination testing. On day 20th, the rats were sacrificed, and the tendon tissue was isolated for macroscopic scoring, microscopic (H&E, Masson's trichrome, Ki67, p53) analyses, and cytokine secretion levels. The levels of macroscopic parameters, including thermal hyperalgesia, mechanical and cold allodynia, deterioration of motor coordination, tendon adhesion score, and microscopic indices, namely histological adhesion, vascular prominence and angiogenesis, and Ki67 and p53 levels, as well as fibrotic and inflammatory biomarkers (IL-6, TNF-α, TGF-ß, VEGF) were significantly increased in the vehicle group compared to the sham group (P < 0.05-0.001 for all cases). In contrast, the administration of noscapine (0.2, 0.6, and 1.8 mg/kg) attenuated the pain, fibrosis, and inflammatory indices in a dose-dependent manner compared to the vehicle group (P < 0.05-0.001). Histological research indicated that noscapine 0.6 and 1.8 mg/kg had the most remarkable healing effects. Interestingly, two higher doses of noscapine had impacts similar to those of the positive control group in both clinical and paraclinical assessments. Taken together, our findings suggested that noscapine could be a promising medicine for treating tendinopathies.

A Novel Tendon Injury Model, Induced by Collagenase Administration Combined with a Thermo-Responsive Hydrogel in Rats, Reproduces the Pathogenesis of Human Degenerative Tendinopathy.

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

Anti-inflammatory effects of sericin and swimming exercise in treating experimental Achilles tendinopathy in rat.

The aim of this study was to assess the effectiveness of combining sericin with swimming exercise as a treatment for type-I collagenase-induced Achilles tendinopathy (AT) in rats, with a focus on inflammatory cytokines. An experimental AT model was established using type-I collagenase in male Sprague-Dawley rats, categorized into five groups: Group 1 (Control + Saline), Group 2 (AT), Group 3 (AT + exercise), Group 4 (AT + sericin), and Group 5 (AT + sericin + exercise). Intratendinous sericin administration (0.8 g/kg/mL) took place from days 3 to 6, coupled with 30 min daily swimming exercise sessions (5 days/week, 4 weeks). Serum samples were analyzed using ELISA for tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-10 (IL-10), and total antioxidant-oxidant status (TAS-TOS), alongside histopathological and immunohistochemical assessments of Achilles tendon samples. Elevated TNF-α and IL-1ß and decreased IL-10 levels were evident in Group 2; Of these, TNF-α and IL-1ß were effectively reduced and IL-10 increased across all treatment groups, particularly groups 4 and 5. Serum TAS was notably lower in Group 2 and significantly increased in Group 5 compared to Group 2. Histopathologically, Group 2 displayed severe degeneration, irregular fibers, and round cell nuclei, while Group 5 exhibited decreased degeneration and spindle-shaped fibers. The Bonar score increased in Group 2 and decreased in groups 4 and 5. Collagen type-I alpha-1 (Col1A1) expression was notably lower in Group 2 (P = 0.001) and significantly increased in groups 4 and 5 compared to Group 2 (P = 0.011 and 0.028, respectively). This study underscores the potential of sericin and swimming exercises in mitigating inflammation and oxidative stress linked to AT pathogenesis, presenting a promising combined therapeutic strategy.

Carpaine alleviates tendinopathy in mice by promoting the ubiquitin-proteasomal degradation of p65 via targeting the E3 ubiquitin ligase LRSAM1.

BACKGROUND: Currently, there are no specific drugs or targets available for the treatment of tendinopathy. However, inflammation has recently been found to play a pivotal role in tendinopathy progression, thereby identifying it as a potential therapeutic target. Carpaine (CA) exhibits potential anti-inflammatory pharmacological properties and may offer a therapeutic option for tendinopathy. PURPOSE: This study aimed to investigate the effectiveness of CA in addressing tendinopathy and uncovering its underlying mechanisms. METHODS: Herein, the efficacy of CA by local administration in vivo in comparison to the first-line drug indomethacin was evaluated in a mouse collagenase-induced tendinopathy (CIT) model. Furthermore, IL-1ß induced a simulated pathological inflammatory microenvironment in tenocytes to investigate its underlying mechanisms in vitro. Further confirmation experiments were performed by overexpressing or knocking down the selective targets of CA in vivo. RESULTS: The findings demonstrated that CA was dose-dependent in treating tendinopathy and that the high-dose group outperformed the first-line drug indomethacin. Mechanistically, CA selectively bound to and enhanced the activity of the E3 ubiquitin ligase LRSAM1 in tendinopathy. This effect mediated the ubiquitination of p65 at lysine 93, subsequently promoting its proteasomal degradation. As a result, the NF-κB pathway was inactivated, leading to a reduction in inflammation of tendinopathy. Consequently, CA effectively mitigated the progression of tendinopathy. Moreover, the LRSAM1 overexpression demonstrated effectiveness in mitigating the tendinopathy progression and its knockdown abolished the therapeutic effects of CA. CONCLUSION: CA attenuates the progression of tendinopathy by promoting the ubiquitin-proteasomal degradation of p65 via increasing the enzyme activity of LRSAM1. The exploration of LRSAM1 has also unveiled a new potential target for treating tendinopathy based on the ubiquitin-proteasomal pathway.

Therapeutic potential of ginsenoside compound K in managing tenocyte apoptosis and extracellular matrix damage in diabetic tendinopathy.

The prevalence of tendinopathy in patients with diabetes is well documented. Despite efforts to improve diabetes management, there is a lack of research on therapeutic agents targeting the core features of tendinopathy, namely, tenocyte apoptosis and extracellular matrix (ECM) damage. In this study, we investigated the potential of ginsenoside compound K (CK), known for its antidiabetic properties, to mitigate tenocyte apoptosis, inflammation, oxidative stress, and the metalloproteinase (MMP) system under hyperglycemic conditions. Our research also aimed to unravel the molecular mechanism underlying the effects of CK. The assessment of apoptosis involved observing intracellular chromatin condensation and measuring caspase 3 activity. To gauge oxidative stress, we examined cellular ROS levels and hydrogen peroxide and malondialdehyde concentrations. Western blotting was employed to determine the expression of various proteins. Our findings indicate that CK treatment effectively countered high glucose-induced apoptosis, inflammation, and oxidative stress in cultured tenocytes. Furthermore, CK normalized the expression of MMP-9, MMP-13, and TIMP-1. Notably, CK treatment boosted the expression of PPARγ and antioxidant enzymes. We conducted small interfering (si) RNA experiments targeting PPARγ, revealing its role in mediating CK's effects on tendinopathy features in hyperglycemic tenocytes. In conclusion, these in vitro results offer valuable insights into the potential therapeutic role of CK in managing tendinopathy among individuals with diabetes. By addressing crucial aspects of tendinopathy, CK presents itself as a promising avenue for future research and treatment development in this domain.

A prospective study of 100 patients with rotator cuff tendinopathy showed no correlation between subacromial bursitis and the efficacy of ultrasound-guided corticosteroid injection.

OBJECTIVES: The objective of this study was to determine whether the presence of subacromial bursitis in patients with rotator cuff tendinopathy (RCT) was associated with a better outcome after ultrasound (US)-guided subacromial corticosteroid injection. METHODS: A single-center prospective study was performed including patients referred for subacromial injection to manage RCT. At baseline, all patients received an US-guided intra-bursal injection of betamethasone (1 ml). The primary endpoint was reduced pain 3 months (M3) after the procedure: a good responder was defined by a decrease in Visual Analogue Scale pain of more than 30%. Secondary endpoints included functional recovery assessed by the Oxford Shoulder Score (OSS) and clinical success at 6 weeks (W6). We also explored the association between good clinical response and other factors, such as US or X-ray features. RESULTS: One hundred patients were included and 49 presented with subacromial bursitis. At M3, 60% of patients (54/100) were considered good responders. The rate of good responders did not differ between the bursitis and non-bursitis groups (p = 0.6). During follow-up, OSS improved over time whether bursitis was present or not. We did not find any US or X-ray features significantly associated with a favorable clinical outcome. CONCLUSION: The presence of subacromial bursitis did not influence clinical outcomes at 3 months post-subacromial injection in patients suffering from RCT. CLINICAL RELEVANCE STATEMENT: The presence of subacromial bursitis did not influence clinical outcomes at 3 months post-subacromial corticosteroid injection in patients with rotator cuff tendinopathy. For patient management, looking for ultrasonographic signs of bursitis does not appear relevant for the indication of the injection. KEY POINTS: • Ultrasound-guided subacromial corticosteroid injections led to a significant improvement in 60% of patients suffering from rotator cuff tendinopathy. • The presence of subacromial bursitis was not associated with better improvement at 3 months post-injection. • Except for the Minnesota score referring to job satisfaction, we did not find any baseline clinical, X-ray, or ultrasound characteristics associated with a successful outcome.

Fluoroquinolone-associated adverse events of interest among hospitalized veterans affairs patients with community-acquired pneumonia who were treated with a fluoroquinolone: A focus on tendonitis, Clostridioides difficile infection, and aortic aneurysm.

STUDY OBJECTIVE: The objectives of this study were to (i) quantify the incidence of three concerning fluoroquinolone adverse events of interest (FQAEI, i.e., adverse tendon event (TE), clostridioides difficile infection (CDI), and aortic aneurysm/dissection (AAD)), (ii) identify the patient-level factors that predict these events, and (iii) develop clinical risk scores to estimate the predicted probabilities of each FQAEI based on patient-level covariates available on clinical presentation. DESIGN: Retrospective cohort study. SETTING: Upstate New York Veterans' Healthcare Administration from 2011 to 2016. PATIENTS: Hospitalized patients with community-acquired pneumonia receiving care in the Upstate New York Veterans' Healthcare Administration from 2011 to 2016. INTERVENTION: N/A. MEASUREMENTS: The outcomes of interest for this study were the occurrence of TE, CDI, and AAD. We also evaluated a composite of these three outcomes, FQAEI. MAIN RESULTS: The study population consisted of 1071 patients. The overall incidence of FQAEI, TE, AAD, and CDI was 6.5%, 1.8%, 4.5%, and 0.3%, respectively. For each outcome evaluated, the probability of the event of interest was predicted by the presence of certain comorbidities, previous healthcare exposure, choice of specific FQ antibiotic, or therapy duration. Concomitant steroids, pneumonia in preceding 180 days, and creatinine clearance <30 mL/min predicted FQAEI. CONCLUSIONS: Individual frequencies of three important FQAEIs were quantified, and risk scores were developed to estimate the probabilities of experiencing these events to help clinicians individualize treatment decisions for patients and reduce the potential risks of select FQAEIs.

Examining the Potential of Vitamin C Supplementation in Tissue-Engineered Equine Superficial Digital Flexor Tendon Constructs.

Because equine tendinopathies are slow to heal and often recur, therapeutic strategies are being considered that aid tendon repair. Given the success of utilizing vitamin C to promote tenogenesis in other species, we hypothesized that vitamin C supplementation would produce dose-dependent improvements in the tenogenic properties of tendon proper (TP) and peritenon (PERI) cells of the equine superficial digital flexor tendon (SDFT). Equine TP- and PERI-progenitor-cell-seeded fibrin three-dimensional constructs were supplemented with four concentrations of vitamin C. The gene expression profiles of the constructs were assessed with 3'-Tag-Seq and real-time quantitative polymerase chain reaction (RT-qPCR); collagen content and fibril ultrastructure were also analyzed. Moreover, cells were challenged with dexamethasone to determine the levels of cytoprotection afforded by vitamin C. Expression profiling demonstrated that vitamin C had an anti-inflammatory effect on TP and PERI cell constructs. Moreover, vitamin C supplementation mitigated the degenerative pathways seen in tendinopathy and increased collagen content in tendon constructs. When challenged with dexamethasone in two-dimensional culture, vitamin C had a cytoprotective effect for TP cells but not necessarily for PERI cells. Future studies will explore the effects of vitamin C on these cells during inflammation and within the tendon niche in vivo.

Combined extract (Curcuma longa-Glycyrrhiza glabra) alleviates the inflammations of Achilles tendinopathy in Wistar rats.

OBJECTIVE: Achilles tendinopathy is a frequent pathological condition in adults with overused ankles, causing microtrauma, inducing tenocyte apoptosis and inflammatory response. Common treatment involves oral prescription or injection of anti-inflammatory agents, surgery, or shock-wave therapy. However, prolonged administration is not advisable due to adverse effects. Therefore, a novel and safe regimen is needed. Curcuma longa and Glycyrrhiza glabra extracts are known for their anti-inflammatory effects owing to their active compounds (curcumin and glycyrrhizin, respectively). This study aimed to determine the effect of combined extracts of Curcuma longa and Glycyrrhiza glabra on tendon healing in an animal model of Achilles tendinopathy (Wistar rats). MATERIALS AND METHODS: This study took place from February to May 2022 and compared the regimens administered to 32 animal models of Wistar rats with 4 healthy rats as a control group to determine the most effective therapeutic regimen: immobilization, immobilization with ibuprofen, or immobilization with the combined extract. The outcomes were measured to find which intervention provided the lowest inflammatory markers [High Mobility Group Box-1 (HMGB-1), Tumor Necrosis Factor-α (TNF-α), Chemokin motif ligand 12 (CXCL-12)], and improved tissue morphology represented by the BONAR score, decreased cross-sectional area (CSA), and increased Macrophage 2 (M2) differentiation. RESULTS: After Achilles tendinopathy was induced, total immobilization (I1) was proven to be the most effective with the lowest CSA, whereas immobilization+175 mg/kg Curcuma longa+110 mg/kg Glycyrrhiza glabra extract (I5) was the most effective with the lowest HMGB-1 levels and the lowest CXCL-12 levels. Immobilization+131 mg/kg Curcuma longa+82.5 mg/kg Glycyrrhiza glabra extract (I6) was the most effective with the lowest Bonar score, while immobilization+87.5 mg/kg Curcuma longa+55 mg/kg Glycyrrhiza glabra extract (I7) was proven to be the most effective with the highest M2 coverage area and the lowest TNF-α levels. CONCLUSIONS: We found that combined extract therapy was the most effective intervention for treating Achilles tendinopathy due to its ability to provide the lowest inflammatory markers.

The JUMPFOOD study: additional effect of hydrolyzed collagen and vitamin C to exercise treatment for patellar tendinopathy (jumper's knee) in athletes-study protocol for a double-blind randomized controlled trial.

BACKGROUND: Patellar tendinopathy (PT) is a common problem in jumping athletes. Management can be challenging and treatment outcome is not always successful. In combination with tendon loading exercises, hydrolyzed collagen/vitamin C supplementation appears to have a promising effect on the recovery of tendinopathy. The aim of this study is to evaluate whether the use of oral supplementation of hydrolyzed collagen and vitamin C in combination with progressive tendon loading exercises (PTLE) is superior to PTLE and placebo on VISA-P score (which rates pain, function, sports participation) after 24 weeks for athletes with PT. METHODS: The JUMPFOOD study is a double-blinded, two-armed randomized controlled trial, in which the effectiveness of oral supplementation of hydrolyzed collagen/vitamin C combined with PTLE compared to PTLE with placebo on pain and recovery of function in athletes with PT will be investigated. Seventy-six athletes aged 16-40 years, with symptoms of PT for at least 12 weeks, who play sports at least once a week will be included. All participants will receive education, advice with regard to load management and a PTLE program according to the Dutch guidelines for anterior knee pain. In addition, the intervention group will receive daily 10 g hydrolyzed collagen and 40 mg vitamin C supplementation for 24 weeks whereas the control group receives 10 g maltodextrin placebo supplementation. Measurements will take place at baseline and at 12 and 24 weeks' follow-up. Primary outcome is the VISA-P score, which evaluates pain, function, and sports participation. For secondary outcome measures, data with regard to pain during functional tests, flexibility measurements, blood withdrawals, imaging characteristics of the tendon, and health questionnaires will be collected. During the follow-up period, participants will register sports participation, amount of training and tendon load, pain during sports, co-medication, and side-effects in a digital weekly diary. DISCUSSION: The JUMPFOOD study is the first large RCT to study the effectiveness of hydrolyzed collagen/vitamin C supplementation in combination with the PTLE program in athletes with patellar tendinopathy. If supplementation of collagen/vitamin C appears to be effective, this treatment can be implemented in daily sports medicine practice to improve the treatment outcome of patients with PT. TRIAL REGISTRATION: ClinicalTrials.gov NCT05407194. Registered on 7 June 2022.

Can Achilles tendinosis be treated effectively with lidocaine and glucose infiltrations, and if so, is the effect lasting? A longitudinal, observational on 27 consecutive patients.

OBJECTIVE: Our aim was to add to the small but growing body of evidence on the effectiveness of ultrasound-guided Achilles intratendinous hyperosmolar dextrose prolotherapy and introduce a novel, preceding step of paratenon hydrodissection with lidocaine in patients with chronic Achilles tendinosis resistant to rehabilitation therapy. METHODS: We conducted a longitudinal, observational study on 27 consecutive patients diagnosed with Achilles tendinosis, in whom conservative treatment, ie, physiotherapy or shock wave therapy, had failed. A 2% lidocaine paratenon anesthesia and hydrodissection was followed by ultrasound-guided, intratendinous injections of 25% glucose every 5 weeks. Visual analogue scales (VAS) were used for pain assessment at rest, for activities of daily living, and after moderate exercise at the begining and at the end of the treatment. Moreover, tendon thickness and vascularisation were recorded at baseline and final treatment consultation. Effectiveness was estimated from scoring and relative pain reduction using a 95% CI. The non-parametric Wilcoxon test and a general linear model for repeated measures were applied. Statistical significance was established as p < 0.05. RESULTS: A median of 5 (1-11) injection consultations per patient were required. Pain scores decreased significantly in all three conditions (p < 0.001). Relative reductions were 75% in pain at rest (95% CI;61-93%), 69% in pain with daily living activities (95% CI; 55-83%), and 70% in pain after moderate exercise (95% CI; 57-84%). Tendon neo-vascularisation was significantly reduced (p < 0.001). We did not observe significant changes in tendon thickness (p = 0.083). CONCLUSIONS: Achilles tendinosis treatment with paratenon lidocaine hydrodissection and subsequent prolotherapy with hyperosmolar glucose solution is safe, effective, inexpensive, and virtually painless with results maintained over time.

Inhibition of IKKß via a DNA-Based In Situ Delivery System Improves Achilles Tendinopathy Healing in a Rat Model.

BACKGROUND: The inhibition of IKKß by the inhibitor 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3-pyridine carbonitrile (ACHP) is a promising strategy for the treatment of Achilles tendinopathy. However, the poor water solubility of ACHP severely hinders its in vivo application. Moreover, the effective local delivery of ACHP to the tendon and its therapeutic effects have not been reported. PURPOSE: To investigate the therapeutic effects of IKKß inhibition via injection of ACHP incorporated into a DNA supramolecular hydrogel in a collagenase-induced tendinopathy rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Dendritic DNA, a Y-shaped monomer, and a crosslinking monomer were mixed with ACHP and self-assembled into an ACHP-DNA supramolecular hydrogel (ACHP-Gel). The effects of ACHP-Gel in tendon stem/progenitor cells were investigated via RNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 120 collagenase-induced rats were randomly assigned to 5 groups: blank, phosphate-buffered saline (PBS), DNA-Gel, ACHP, and ACHP-Gel. Healing outcomes were evaluated using biomechanic and histologic evaluations at 4 and 8 weeks. RESULTS: ACHP-Gel enhanced the solubility of ACHP and sustained its release for ≥21 days in vivo, which significantly increased the retention time of ACHP and markedly reduced the frequency of administration. RNA sequencing and qRT-PCR showed that ACHP effectively downregulated genes related to inflammation and extracellular matrix remodeling and upregulated genes related to tenogenic differentiation. The cross-sectional area (P = .024), load to failure (P = .002), stiffness (P = .039), and elastic modulus (P = .048) significantly differed between the ACHP-Gel and PBS groups at 8 weeks. The ACHP-Gel group had better histologic scores than the ACHP group at 4 (P = .042) and 8 weeks (P = .009). Type I collagen expression (COL-I; P = .034) and the COL-I/collagen type III ratio (P = .015) increased while interleukin 6 expression decreased (P < .001) in the ACHP-Gel group compared with the ACHP group at 8 weeks. CONCLUSION: DNA supramolecular hydrogel significantly enhanced the aqueous solubility of ACHP and increased its release-retention time. Injection frequency was markedly reduced. ACHP-Gel suppressed inflammation in Achilles tendinopathy and promoted tendon healing in a rat model. CLINICAL RELEVANCE: ACHP-Gel injection is a promising strategy for the treatment of Achilles tendinopathy in clinical practice.

Ultrasound guided lavage with corticosteroid injection versus sham lavage with and without corticosteroid injection for calcific tendinopathy of shoulder: randomised double blinded multi-arm study.

OBJECTIVE: To compare treatment effects between ultrasound guided lavage with corticosteroid injection and sham lavage with and without corticosteroid injection in patients with calcific tendinopathy of the shoulder. DESIGN: Pragmatic, three arm, parallel group, double blinded, sham controlled, randomised, superiority trial with repeated measurements over 24 months. SETTING: Six hospitals in Norway and Sweden. PARTICIPANTS: 220 adults with calcific tendinopathy of the shoulder, persistent for at least three months. INTERVENTIONS: Ultrasound guided deposit lavage plus subacromial injection of 20 mg triamcinolone acetonide and 9 mL 1% lidocaine hydrochloride (lavage+steroid); sham lavage plus subacromial injection of 20 mg triamcinolone acetonide and 9 mL 1% lidocaine hydrochloride (sham lavage+steroid); or sham lavage plus subacromial injection of 10 mL 1% lidocaine hydrochloride (sham). All patients received a physiotherapeutic treatment regimen consisting of four home exercises. MAIN OUTCOME MEASURES: The primary outcome was the result on the 48 point scale (0=worst; 48=best) of the Oxford Shoulder Score (OSS) at four month follow-up. Secondary outcomes included measurements on the short form of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) and of pain intensity up to 24 months. The influence of the size of the deposit at baseline and of the persistence or disappearance of the deposit was investigated. RESULTS: Data from 218 (99%) participants were included in the primary analysis. Differences between groups on the OSS at four months were not significant: lavage+steroid versus sham 0.2 (95% confidence interval -2.3 to 2.8; P=1.0); sham lavage+steroid versus sham 2.0 (-0.5 to 4.6; P=0.35); lavage+steroid versus sham lavage+steroid -1.8 (-4.3 to 0.7; P=0.47). After four months, 143 patients with insufficient treatment effect received supplementary treatment. At 24 months, none of the study procedures was superior to sham. No serious adverse events were reported. CONCLUSIONS: This study found no benefit for ultrasound guided lavage with a corticosteroid injection or for sham lavage with a corticosteroid injection compared with sham treatment in patients with calcific rotator cuff tendinopathy of the shoulder. TRIAL REGISTRATION: NCT02419040EudraCT 2015-002343-34; Ethical committee Norway 2015-002343-34; Ethical committee Sweden 2015/79-31; Clinicaltrials.gov NCT02419040.

Complication of barbotage, acute calcific bursitis treated successfully.

One of the most common causes of chronic shoulder pain that significantly impairs patients' quality of life is rotator cuff calcific tendinitis. The supportive approach of analgesics, anti-inflammatory medications, and physiotherapy is preferred to treat mild symptoms. However, severe intractable symptoms necessitate alternative treatment, and ultrasonography-guided percutaneous barbotage is regarded as an effective treatment technique due to its minimal invasiveness, low cost, and rapid significant pain relief. Post-barbotage complications are reported as acute calcific bursitis along with infection, bleeding, and tendon rupture. In our case, a 41-year-old female presented with a substantial amount of pain shortly after barbotage, which was diagnosed as acute calcific bursitis, a complication of the procedure. Subacromial-subdeltoid steroid injection was used successfully to treat this condition.

Silk protein sericin: a promising therapy for Achilles tendinopathy-evidence from an experimental rat model.

OBJECTIVE: This study investigated the efficacy of sericin in treating experimental Achilles tendinopathy (AT) in rats via the transforming growth factor-beta (TGF-ß)/mothers against decapentaplegic (Smad) pathway compared with diclofenac sodium (DS). METHOD: An AT model was induced in rats using collagenase enzyme type I and divided into 5 groups: C (control), AT (diseased control), ATS (AT treated with sericin), ATN (AT treated with DS), and ATSN (AT treated with sericin and DS). Sericin injection was given on the 3rd and 6th days by intratendinous injection (0.8 g/kg/mL), and DS was administered for 14 days by oral gavage (1.1 mg/kg/day). Serum concentrations of total oxidant-antioxidant status (TOS-TAS), TGF-ß1, decorin, Smad2, and connective tissue growth factor (CTGF) were measured. Histopathologic and immunohistochemical (IHC) studies were conducted on Achilles tendon samples. RESULTS: The TOS, oxidative stress index (OSI), TGF-ß1, Smad2, CTGF, and decorin serum concentrations were significantly higher in AT than in C and significantly lower in ATS than in AT (P<0.05). Histopathological examination revealed that irregular fibers, degeneration, and round cell nuclei were significantly elevated in AT. Spindle-shaped fibers were similar to those in C, and degeneration was reduced in ATS. TGF-ß1 and Smad2/3 expression was increased, and collagen type I alpha-1 (Col1A1) expression was decreased in AT vs. C (P=0.001). In the ATS, TGF-ß1 and Smad2/3 expression decreased, and Col1A1 expression increased. The Bonar score significantly increased in the AT group (P =0.001) and significantly decreased in the ATS group (P =0.027). CONCLUSION: Sericin shows potential efficacy in reducing oxidative stress and modulating the TGF-ß/Smad pathway in experimental AT models in rats. It may be a promising therapeutic agent for AT, warranting further clinical studies for validation. Key Points • This study revealed that sericin mitigates AT-induced damage through the TGF-ß/Smad pathway in an AT rat model. • ELISA and IHC investigations corroborated the effectiveness of sericin via the pivotal TGF-ß/Smad pathway in tissue repair. • Evidence indicates that sericin enhances collagen synthesis,shapes tendon fiber structure, and diminishes histopathological degeneration. • Sericin's antioxidant properties were reaffirmed in its AT treatment application.

Terminating Corticosteroid Injection in Tendinopathy? Hasta la Vista, Baby.

SYNOPSIS: Two recent randomized-controlled trials showed promising results of local corticosteroid injections combined with exercise therapy for Achilles tendinopathy and plantar fasciopathy. Should clinicians go back to using corticosteroid injections to treat tendinopathy? Are corticosteroids back (baby)? In this viewpoint we critically appraise the new evidence and humbly share our clinical reasoning when advising athletes about corticosteroid injections in practice. Our goal is to help clinicians decide what to do and what to recommend to patients. We prioritize the risk for higher recurrence rates and tendon rupture when weighing the reasonable treatment options for tendinopathy, and recommend against using corticosteroid injections. The best systematic review evidence shows that local corticosteroid injections are not effective for tendinopathies after the first few weeks, and produce worse long-term outcomes compared to other treatments. For now, we consider corticosteroid injections remain terminated. J Orthop Sports Phys Ther 2023;53(11):1-4. Epub: 28 July 2023. doi:10.2519/jospt.2023.11875.

Is Ultrasound (US)-Guided Platelet-Rich Plasma Injection More Efficacious as a Treatment Modality for Lateral Elbow Tendinopathy Than US-Guided Steroid Injection?: A Prospective Triple-Blinded Study with Midterm Follow-up.

Background: Lateral elbow tendinopathy (LET) has an array of modalities described for its management. The present study analyzed two modalities used for managing the condition. Methods: The present study included 64 non-athletes with LET who failed conservative treatment that included avoiding strenuous activities, ice-fomentation, non-steroidal anti-inflammatory drugs, bracing, and physiotherapy for 6 months. A random allocation of the participants was done, with one group injected with platelet-rich plasma (PRP) and the other group with corticosteroids. The procedure was performed by the same blinded orthopedic surgeon after localizing the pathology using ultrasound. Visual analog scale (VAS) scores, disabilities of the arm, shoulder and hand (DASH) scores, Patient-Rated Tennis Elbow Evaluation (PRTEE) scores, and handgrip strengths were recorded by blinded observers other than the surgeon administering the injection. Results: The average age of the patients was 40 years. The mean VAS score at the latest follow-up of 2 years in the PRP group was 1.25 and it was significantly better than the score of 3.68 in the steroid group (p < 0.001). The mean DASH score at the latest follow-up of 2 years in the PRP group was 4.00 and it was significantly better than the score of 7.43 in the steroid group (p < 0.001). The mean PRTEE score at the latest follow-up of 2 years in the PRP group was 3.96 and it was significantly better than the score of 7.53 in the steroid group (p < 0.001). The scores were better in the steroid group at a short-term follow-up of 3 months (p < 0.05), while they were better in the PRP group at a long-term follow-up of 2 years (p < 0.05). Hand-grip strength was comparable in the PRP group (84.43 kg force) and steroid group (76.71 kg force) at the end of the 2-year follow-up with no statistically significant difference (p = 0.149). Conclusions: Corticosteroid injections alleviated symptoms of LET over short-term follow-up providing quicker symptomatic relief; however, the effect faded off over the long term. PRP injections provided a more gradual but sustained improvement over the long-term follow-up, indicating the biological healing potential of PRP.

Effects of adjuvant application of corticosteroid and ozone after ultrasound-guided puncture and lavage for the treatment of rotator cuff calcific tendinitis: study protocol for a non-inferiority randomized controlled trial.

BACKGROUND: Steroid injection after percutaneous irrigation of calcific deposits is a common method for the treatment of rotator cuff calcific tendinitis (RCCT). However, steroids may prevent calcification resorption and cause potentially irreversible damage to tendons. Recent studies have confirmed the positive effects of ozone injection in shoulder tendinopathies, but no RCCTs have been reported. Thus, our study aims to evaluate the non-inferiority of ozone versus steroid injection. METHODS: This is a prospective, randomized, parallel control and non-inferiority trial. A total of 100 patients with unilateral symptomatic RCCT will be enrolled and randomized in a 1:1 ratio to two groups: ultrasound-guided injection with ozone or corticosteroid. The primary outcome is the numeric rating scale for pain (NRS) at 1 week and 3 months following the procedure. Secondary outcomes include a multi-dimensional evaluation of shoulder disability and quality of life improvement, the degree of calcification absorption after treatment, and the number of multiple treatments. DISCUSSION: The results of this study will provide short-term and long-term evidence for the effectiveness of ozone treatment in RCCT in relieving pain or improving shoulder function. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200063469. Registered on 7 September 2022.