Search Results (33)

Rotator cuff tears are a leading cause of shoulder pain and dysfunction, yet the molecular mechanisms that link tendon injury to inflammation and nociceptive signaling remain poorly understood. Netrin-1, a classical axon guidance cue signaling through dependence receptors UNC5B and Neogenin-1, has been implicated in both neuronal plasticity and inflammatory processes, but its role in tendon pathology has not been explored. A rat supraspinatus tear model was employed to assess, in vivo, the expression of genes encoding netrin-1 (Ntn1) and its receptors (Unc5b and Neo1) at 0, 7, 14, 28, and 56 days post-injury (n = 10 per time point). Primary rat tenocytes isolated from rotator cuff tissue were treated in vitro with recombinant netrin-1, and transcriptional changes in genes encoding TNF-α (Tnfa), IL-6 (Il6), MMP-1 (Mmp1), and MMP-3 (Mmp3) were quantified by qRT-PCR. Separately, human iPSC-derived sensory neurons were exposed to netrin-1, and dose- and time-dependent effects on neurite outgrowth were measured at 4 and 14 days in culture. In injured tendons, Ntn1 mRNA increased significantly at day 14 (p = 0.010) and 28 (p = 0.042), Unc5b at day 7 (p = 0.002) and 14 (p < 0.001), and Neo1 at day 14 (p < 0.001) versus intact controls. Tenocyte exposure to 500 ng/mL netrin-1 induced transient upregulation of Tnfa (3 h, p = 0.023; 6 h, p = 0.009) and Il6 (3 h–24 h, all p < 0.013), as well as Mmp3 (3–24 h, p < 0.043) and Mmp1 (6 h–24 h, p < 0.024); no induction was observed at 50 ng/mL. In sensory neurons, 50 ng/mL of netrin-1 enhanced neurite extension at day 4 (p = 0.006) but not at 500 ng/mL or at day 14 for either dose. Netrin-1 and its receptors are upregulated in a rat rotator cuff tear model, and netrin-1 elicits distinct pro-inflammatory and matrix-remodeling responses in tenocytes while promoting early neurite growth in sensory neurons. These findings suggest netrin-1 as a key modulator of tendon inflammation, matrix turnover, and peripheral nerve plasticity following injury. Full article

Objective: This descriptive systematic review aimed to assess in the available literature on the current application and overall performance of Artificial Intelligence (AI) models in the diagnosis and classification of Rotator Cuff Tears (RCTs) using MRIs. Methods: The systematic review was performed by two of the authors from 2020 to November 2024. Only diagnostic studies involving AI application to MRI images of the rotator cuff were considered, including supraspinatus and biceps tears. Studies evaluating AI applications to Ultrasound or X-ray, or including only healthy rotator cuffs, were not analyzed in this paper. Results: The coronal plane in the T2 sequence emerged as the predominant imaging protocol, with the VGG network being the most widely utilized AI model. The studies included in this research exhibited a solid performance of the AI models with accuracy, ranging from 71.0% to 100%. The statistical analysis revealed no significant differences (p > 0.05) in accuracy, sensitivity, specificity, or precision between AI and human experts across studies that included such comparisons. Conclusions: While AI can significantly improve diagnostic efficiency and workflow optimization, future studies must focus on external validation, regulatory approval, and AI-human collaboration models to ensure safe and effective integration into orthopedic imaging. Full article

Background: Quantitative magnetic resonance imaging (MRI) techniques such as T₂ mapping may detect early tendon changes following biologic therapies. This study aimed to assess the structural remodeling of the supraspinatus tendon using mean T₂ values and T₂ distribution profiles after an ultrasound (US)-guided single platelet-rich plasma (PRP) injection. Methods: Twenty-six patients with symptomatic supraspinatus tendinopathy were divided into tendinosis (n = 9) and partial tear (n = 13) groups. T₂ mapping and clinical evaluations (shoulder pain and disability index questionnaire (SPADI), Constant-Murley score) were conducted at baseline and 6 months post-PRP. Mean T₂ values were measured in three tendon segments (lateral, middle, and medial), and T₂ profiles were compared to asymptomatic controls. Results: Clinical outcomes showed significant improvement in both the tendinosis and partial tear groups at the 6-month follow-up. Although no significant changes were observed in the mean T₂ relaxation times across tendon segments following PRP treatment, T₂ distribution profiling revealed statistically significant alterations in both groups. In the tendinosis group, post-treatment T₂ profiles approached those of the asymptomatic controls, suggesting structural remodeling consistent with tendon healing. Conclusions: T₂ mapping is an effective tool for detecting tendon remodeling following PRP therapy. Structural improvements indicative of tissue healing were observed in cases of tendinosis, but not in partial tendon tears. These findings support the use of T₂ mapping—particularly the T₂ distribution profiling—as a quantitative biomarker for assessing treatment response to PRP. Full article

Background/Objectives: This study aimed to identify the risk factors for retears after arthroscopic rotator cuff repair (ARCR) and to establish a hierarchy of their importance using machine learning. Methods: This study analyzed 788 primary ARCR cases performed by a single senior surgeon from January 2016 to December 2022. The condition of the repaired supraspinatus was assessed via magnetic resonance imaging (MRI) or sonography within 2 years after surgery. In total, 27 preoperative demographic, objective, and subjective clinical variables were analyzed using five well-established models: Extreme Gradient Boosting (XGBoost), Random Forest (RF), Support Vector Machine (SVM), Neural Network (NN), and logistic regression (LR). The models were trained on an 8:2 split training and test set, with three-fold validation. The primary metric for evaluating model performance was the area under the receiver operating characteristic curve (AUC). The top five influential features were extracted from the best-performing models. Univariate and multivariate LRs were performed independently as a reference. Results: The overall retear rate was 11.9%. The two best-performing prediction models were RF (validation AUC = 0.9790) and XGBoost (validation AUC = 0.9785). Both models consistently identified the tear size in the medial–lateral (ML) and anterior–posterior (AP) dimensions, full-thickness tears, and BMI among the top five risk factors. XGBoost uniquely included female sex, while RF highlighted the visual analogue scale (VAS) pain score. While conventional univariate regression indicated multiple significant factors associated with retears (age, full-thickness tear, AP and ML tear size, biceps conditions, fatty infiltration of three rotator cuff muscles, and atrophy of supraspinatus), multivariate analysis demonstrated that only age and the ML tear size are significant factors. Conclusions: Machine learning models demonstrated enhanced predictive accuracy compared to traditional LR in predicting retears, and the importance of risk factors was derived. Tear size, full-thickness tears, BMI, female sex, and VAS pain score emerged as the most influential risk factors. Full article

Background: Because of its anatomy and function, the rotator cuff (RC) is vulnerable to considerable morbidity. The prevalence of RC diseases (RCDs) among the general population is 5–39%, reaching over 30% in patients older than 60. The aim of the present systematic review is to investigate the effects of the use of collagen injections in the treatment of RCDs. Methods: A systematic search of scientific electronic databases (such as PubMed, Scopus and Web of Science) was performed up to November 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two independent authors conducted the search and assessed the articles. The inter-rater reliability for the quality assessment was measured using Cohen’s kappa coefficient, while the Modified Coleman Methodology Score (CMS) was applied to evaluate the methodological quality of the articles included in this systematic review. Results: A total of eight articles were included, with the overall quality of the included articles being evaluated as fair. Despite the use of different types of collagen and injection protocols, as well as the different scores applied, each included study showed clinically relevant improvements. However, given the high degree of heterogeneity of the included studies, we cannot draw conclusions regarding which type of collagen and injection protocol are best for RCD treatment. Discussion: Collagen administration for RCDs seems to be effective at reducing pain and improving function, as well as the tendon structure, especially in partial tears and RC tendinopathy. High-quality, prospective studies with long-term follow-up are necessary to validate the findings of the articles included in this systematic review. Full article

Shoulder and elbow injuries are prevalent among baseball players, particularly pitchers, who experience repetitive eccentric loading of the shoulder, leading to muscle damage and increased injury risk. Nearly 40% of shoulder injuries in baseball occur in pitchers, with many facing low rates of return to sport. The rotator cuff (RC) muscles—supraspinatus (SSP), infraspinatus (ISP), subscapularis (SSC), and teres minor (TMin)—are crucial for shoulder stability, movement, and force generation, particularly in overhead sports. Each RC muscle comprises subregions with distinct biomechanical properties, such as strength, moment arm behavior, and activation patterns. These differences allow for a finely tuned balance between joint stability and mobility. For example, the superior subregion of the ISP significantly contributes to external rotation, a function critical in sports like baseball that require precision and power. During pitching, the SSP, ISP, and SSC stabilize the glenohumeral joint through high activation during explosive phases, such as stride, arm cocking, and arm acceleration. Understanding these functional subregional differences is vital for diagnosing and managing shoulder pathologies like RC tears. Despite advancements, clinicians face challenges in predicting re-injury risks and determining return-to-play readiness for athletes with shoulder injuries. Integrating insights into subregional biomechanics with patient care could enhance outcomes. Tailored interventions—whether surgical or rehabilitative—targeting specific subregions could improve recovery times, reduce re-injury risks, and enable more personalized treatment plans. Such approaches are especially beneficial for athletes, older individuals, and those prone to RC injuries, promoting better long-term shoulder health and performance. The present work aims to highlight some of the research on these subregions and their differences, providing insights to enhance treatment approaches for shoulder injuries. Full article

Background/Objectives: Patients with diabetes have been reported to experience a higher prevalence of shoulder disorders compared to those without diabetes or with other medical conditions. However, the specific types of shoulder injuries and the extent of functional impairment associated with diabetes mellitus remain unclear. This study aimed to assess the association between diabetes and specific shoulder injuries, as well as the degree of functional impairment in affected patients. Methods: A case–control study was conducted involving 136 patients with shoulder functional impairment (UCLA Shoulder Scale ≤ 27). The study included 38 patients with diabetes and 98 non-diabetic controls. Shoulder injuries were diagnosed using ultrasonography, focusing on the supraspinatus tendon, long head of the biceps tendon, subscapularis tendon, and the presence of adhesive capsulitis or rotator cuff tears. Results: Diabetic patients had significantly higher rates of poor shoulder function compared to non-diabetic controls (89.47% vs. 63.26%, adjusted OR [adOR] 5.22, 95% CI 1.57–17.32, p = 0.007). While both groups had high rates of supraspinatus and long head of the biceps tendon injuries (~80%), no significant differences were found between them (p > 0.300). However, diabetic patients were more than three times as likely to have subscapularis tendon injuries (adOR 3.15, 95% CI 1.26–7.90, p = 0.014) and massive rotator cuff tears (adOR 3.76, 95% CI 1.16–12.15, p = 0.027). Additionally, diabetes was associated with a fourfold increased risk of adhesive capsulitis (adOR 4.16, 95% CI 1.20–14.47, p = 0.025). Conclusions: Diabetes mellitus is linked to greater functional and structural deterioration of the shoulder, highlighting the importance of considering diabetes as a risk factor for specific shoulder injuries. Early diagnosis and treatment may improve outcomes for diabetic patients with shoulder disorders. Full article

Rotator cuff tears (RCT) are the most common cause of shoulder pain among adults. “Rotator cuff” refers to the four muscles that cover the shoulder joint: supraspinatus, infraspinatus, subscapularis, and teres minor. These muscles help maintain the rotational movement and stability of the shoulder joint. RCT is a condition in which one or more of these four muscles become ruptured or damaged, causing pain in the arms and shoulders. RCT results from degenerative changes caused by chronic inflammation of the tendons and consequent tendon tissue defects. This phenomenon occurs because of the exhaustion of endogenous tendon stem cells. Tendon regeneration requires rejuvenation of these endogenous tendon stem/progenitor cells (TSPCs) prior to their growth phase. TSPCs exhibit clonogenicity, multipotency, and self-renewal properties; they express classical stem cell markers and genes associated with the tendon lineage. However, specific markers for TSPC are yet to be identified. In this review, we introduce novel TSPC markers and discuss various strategies for TSPC reprogramming. With further research, TSPC reprogramming technology could be adapted to treat age-related degenerative diseases, providing a new strategy for regenerative medicine. Full article

The success of rotator cuff tendon repair relies on both tendon healing and muscle recovery. The objective of this descriptive study was to investigate the regenerative potential of the supraspinatus muscle in rotator cuff tear conditions by quantifying the expression of Pax7, MyoD, and myogenin, basic factors that regulate myogenesis. Muscle biopsies were collected from thirty-three patients aged 34 to 73 years who underwent surgery for a rotator cuff tear affecting the supraspinatus muscle. Among these patients, twenty-seven percent were women, and the age of the lesions ranged from 2 to 72 months post-initial trauma. Biopsies were harvested from the supraspinatus muscle at the end closest to the tendon, and control biopsies were harvested from the ipsilateral deltoid muscle. The densities of immunohistochemically stained Pax7⁺, MyoD⁺, and myogenin⁺ nuclei/mm² were used to estimate the myogenic potential of the muscle. Adjustments were made for patient age and lesion age. We found increased density of MyoD⁺ and myogenin⁺ cells in supraspinatus muscles compared to deltoid muscles (p < 0.001 and p = 0.003, respectively). Regression analyses that combined the density of positive nuclei with patient age showed a continuous increase in Pax7 with age but also a reduction of MyoD and myogenin in older patients. When combined with lesion age, there was a decline in the density of all myogenic markers after an initial rise. Pax7 density continued to be higher in supraspinatus compared to the deltoid muscle, but the density of MyoD and myogenin terminally dropped to a density lower than in the deltoid. Our findings suggest that the supraspinatus muscle in tear conditions showed signs of initial activation of muscle regeneration. When compared to the unaffected deltoid muscle, an apparent reduction in capacity to progress to full muscle fiber maturity was also demonstrated. This pattern of inhibited myogenesis seemed to increase with both patient age and lesion age. Our results on muscle regenerative capacity indicate that younger patients with rotator cuff tears have better chances of muscle recovery and may benefit from early surgical reconstruction. Full article

Background: This study evaluates the clinical efficacy and safety of two ultrasound (US)-guided injections of a 5 mg/1 mL low-molecular-weight peptide (LWP) solution derived from hydrolyzed bovine collagen in patients with supraspinatus partial tendon tears. Methods: A total of 21 patients with symptomatic partial tears of the supraspinatus tendon, detected by US, were consecutively enrolled and received one injection at a baseline visit (T0) and one after two weeks (T1). The primary outcome measure was the visual analogue scale (VAS) for pain. Secondary outcomes were the shoulder pain and disability index (SPADI) total score and the safety of LWP injections. Patients were examined at baseline (T0), at a week 2 follow-up visit (T1), and at a week 12 follow-up visit (T2). Results: A statistically significant improvement was found for both VAS pain and SPADI total scores, between T0 and T2 visits. US-guided injections were well tolerated and, apart from one patient with a progression of a tendon tear, no adverse events were recorded. Conclusions: Intratendinous tear US-guided injection therapy with an LWP solution was found to be safe and effective in improving both pain and shoulder function at a 12-week follow-up visit. The present pilot study should be considered the first step justifying a larger confirmatory investigation. Full article

The positive effect of platelet-rich plasma (PRP) on tendon metabolism has been extensively investigated and proven in vitro. Additionally, in vivo animal studies have correlated the application of PRP with the enhancement of tenocyte anabolic activity in the setting of tendon degeneration. However, less is known about its in vivo effect on human tendon biology. The purpose of the current prospective randomized comparative study was to evaluate the effect of PRP on torn human supraspinatus tendon. Twenty consecutive eligible patients with painful and magnetic resonance imaging (MRI)-confirmed degenerative supraspinatus tendon tears were randomized in a one-to-one ratio into two groups. The patients in the experimental group (n = 10) underwent an ultrasound-guided autologous PRP injection in the subacromial space 6 weeks before the scheduled operation. In the control group (n = 10), no injection was made prior to surgery. Supraspinatus tendon specimens were harvested from the lateral end of the torn tendon during shoulder arthroscopy and were evaluated under optical and electron microscopy. In the control group, a mixed cell population of oval and rounded tenocytes within disorganized collagen and sites of accumulated inflammatory cells was detected. In contrast, the experimental group yielded abundant oval-shaped cells with multiple cytoplasmic processes within mainly parallel collagen fibers and less marked inflammation, simulating the intact tendon structure. These findings indicate that PRP can induce microscopic changes in the ruptured tendon by stimulating the healing process and can facilitate a more effective recovery. Full article

With the increasing occurrence of rotator cuff injuries every year, there is a great need for a reliable treatment option. Wharton’s Jelly contains several components that can positively impact the replacement and repair of musculoskeletal defects. The overall objective of this study is to evaluate the improvement of patient-reported pain scales after applying Wharton’s Jelly (WJ) in rotator cuff defects. Eighty-seven patients with rotator cuff defects who failed at least eight weeks of conservative treatment were selected from the retrospective repository. A total of 2 cc of WJ flowable allograft was applied to the specific affected anatomy, the most common being supraspinatus tendon, biceps tendon insertion, labral tear, and subscapularis tear. No adverse reactions were reported. Statistically significant improvements were found from the initial to Day 90 in all scales. Patient satisfaction was calculated using minimal clinically important differences. No statistically significant differences were found in mean changes between gender, BMI, and age. Scanning electron microscopy images reveal the similarities between the collagen matrix in WJ and the rotator cuff. The significant improvement in patient outcomes coincides with the current literature analyzing WJ applications with other structural defects around the body. WJ is a promising alternative for musculoskeletal defects when the standard of care fails. Full article

The prevalence of partial rotator cuff tears (PRCTs) is high in the general population. Our hypothesis is that barbotage, when associated with platelet-rich plasma (PRP), is an effective method for healing these tears. The aim of this study was to compare the effects of barbotage with or without PRP on the healing of partial supraspinatus tendon tears (PSTTs). This study assessed the Western Ontario Rotator Cuff Index score and ultrasound (US) images at 6 weeks and 6 months after treatment. Patients in both groups showed clinical improvement, with no significant difference in scores at 6 weeks. However, at 6 months, the PRP group exhibited significant improvement (p = 0.019). Both groups experienced a reduction in ST tear size, but the PRP group demonstrated a significant enhancement at 6 weeks and 6 months. In conclusion, the US-guided barbotage technique, whether associated with PRP or saline solution, proved to be an effective treatment for clinical improvement and reduction in the size of PSTT. Better clinical improvement results were observed with PRP at 6 months. The combination of PRP with barbotage was superior in reducing the size of the ST tear at both 6 weeks and 6 months, resulting in complete healing in 79.3% of the tears. Full article

Background and Purpose: Despite the prevalent incidence of re-tear following rotator cuff repair, there is a notable lack of comparative studies investigating the outcomes between patients with re-tear who underwent primary repair versus those who received patch augmentation for large-to-massive tears. We assessed clinical outcomes of these techniques through a retrospective, randomized controlled trial. Methods: 134 patients diagnosed with large-to-massive rotator cuff tears from 2018 to 2021 underwent surgery; 65 had primary repair and 69 had patch augmentation. A total of 31 patients with re-tears were included, split into two groups; Group A (primary repair, 12 patients) and Group B (patch augmentation, 19 patients). Outcomes were evaluated using several clinical scales and MRI imaging. Results: Most clinical scores improved postoperatively in both groups. No significant difference in clinical outcomes was observed between groups, except for pain visual analog scale (P-VAS) scores. P-VAS scores showed greater decrease in the patch-augmentation group, a statistically significant difference. Conclusions: for large-to-massive rotator cuff tears, patch augmentation led to greater decreases in pain than primary repair, despite similar radiographic and clinical results. Greater tuberosity coverage of the supraspinatus tendon footprint may impact P-VAS scores. Full article

Advanced glycation end-products (AGEs) play a critical supportive role during musculoskeletal disorders via glycosylation and oxidative stress. Though apocynin, identified as a potent and selective inhibitor of NADPH oxidase, has been reported to be involved in pathogen-induced reactive oxygen species (ROS), its role in age-related rotator cuff degeneration has not been well clarified. Therefore, this study aims to evaluate the in vitro effects of apocynin on human rotator cuff-derived cells. Twelve patients with rotator cuff tears (RCTs) participated in the study. Supraspinatus tendons from patients with RCTs were collected and cultured. After the preparation of RC-derived cells, they were divided into four groups (control group, control + apocynin group, AGEs group, AGEs + apocynin group), and gene marker expression, cell viability, and intracellular ROS production were evaluated. The gene expression of NOX, IL-6, and the receptor for AGEs (RAGE) was significantly decreased by apocynin. We also examined the effect of apocynin in vitro. The results showed that ROS induction and increasing apoptotic cells after treatment of AGEs were significantly decreased, and cell viability increased considerably. These results suggest that apocynin can effectively reduce AGE-induced oxidative stress by inhibiting NOX activation. Thus, apocynin is a potential prodrug in preventing degenerative changes of the rotor cuff. Full article