Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration.

Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74 000 human single cells were profiled. As results, we found that SPP1+ macrophages, RGCC+ endothelial cells, ACKR1+ endothelial cells and ADAM12+ fibroblasts participated in tendon adhesion formation. Interestingly, despite specific fibrotic clusters in tendon adhesion, FOLR2+ macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells. Furthermore, ACKR1 was verified to regulate FOLR2+ macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26RtdTomato mice to lethally irradiated Ackr1-/- mice (Ackr1-/- chimeras; deficient in ACKR1) and control mice (WT chimeras). Compared with WT chimeras, the decline of FOLR2+ macrophages was also observed, indicating that ACKR1 was specifically involved in FOLR2+ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered a novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.

The subacromial bursa modulates tendon healing after rotator cuff injury in rats.

Rotator cuff injuries result in more than 500,000 surgeries annually in the United States, many of which fail. These surgeries typically involve repair of the injured tendon and removal of the subacromial bursa, a synovial-like tissue that sits between the rotator cuff and the acromion. The subacromial bursa has been implicated in rotator cuff pathogenesis and healing. Using proteomic profiling of bursa samples from nine patients with rotator cuff injury, we show that the bursa responds to injury in the underlying tendon. In a rat model of supraspinatus tenotomy, we evaluated the bursa's effect on the injured supraspinatus tendon, the uninjured infraspinatus tendon, and the underlying humeral head. The bursa protected the intact infraspinatus tendon adjacent to the injured supraspinatus tendon by maintaining its mechanical properties and protected the underlying humeral head by maintaining bone morphometry. The bursa promoted an inflammatory response in injured rat tendon, initiating expression of genes associated with wound healing, including Cox2 and Il6. These results were confirmed in rat bursa organ cultures. To evaluate the potential of the bursa as a therapeutic target, polymer microspheres loaded with dexamethasone were delivered to the intact bursae of rats after tenotomy. Dexamethasone released from the bursa reduced Il1b expression in injured rat supraspinatus tendon, suggesting that the bursa could be used for drug delivery to reduce inflammation in the healing tendon. Our findings indicate that the subacromial bursa contributes to healing in underlying tissues of the shoulder joint, suggesting that its removal during rotator cuff surgery should be reconsidered.

Investigation of the pressure value while performing biceps tenodesis for superior capsuler reconstruction.

BACKGROUND: To compare the histopathological results of biceps tenodesis (BT) performed with normal, low, and high pressures for superior capsule reconstruction (SCR) in rabbits with massive rotator cuff tears. MATERIALS AND METHODS: Thirty rabbits were divided into three groups. Rabbits 1-10 underwent SCR with BT at the same pressure (Group 1), value measured in the groove; 50% lower (Group 2); 50% higher (Group 3). After the 4-week follow-up, shoulder were en-bloc excised and histopathological evaluation was performed with modified Bonar's scale. Results were compared between the groups, statistically. RESULTS: Extracellular matrix were significantly lower in group 2 compared to the other groups (p < 0.05). Cellularity levels were significantly lower in group 2 compared to the other groups (p < 0.05). Group 2 had no difference between the sides (p > 0.05). Group 2 had lower vascularity levels compared to the other groups (p = 0.01). DICSUSSION: When the biceps tendon was in the bicipital groove and in a more mobile state with lower pressure exposure. BT performed with a tension that creates less pressure than the biceps in the groove is more successful in SCR.

The association between a rotator cuff tendon tear and a tear of the long head of the biceps tendon: Chart review study.

Rotator cuff (RC) and long head of the biceps tendon (LHBT) tears are common shoulder problems presented to the orthopedic clinic. The aim of this study was to assess the association between RC and LHBT tears among a Saudi population sample. A total of 243 patients who were diagnosed with shoulder pain due to RC or LHBT tear between 2016 and 2018 using a magnetic resonance imaging scan were included in this study. Females comprised 66% of the sample, and 59% (n = 143) of the shoulders were on the right side. The mean age of the patients was 58 ± 11 years, ranging from 23 to 88 years. A significant association was detected between the LHBT and RC tears (P < 0.001). Out of 26 cases showing RC and LHBT tears, 81% had a full thickness tear, whereas 19% had a partial tear. The LHBT tears were presented significantly in 48% of cases with at least two completely torn RC compared to 10% in cases with one completely torn RC (P < 0.001). The LHBT tear was significantly observed in shoulders with RC tears including the tendons of subscapularis, supraspinatus, and infraspinatus, but not the teres minor (P < 0.001). Both types of tears were presented significantly in senior patients aged more than 65 years compared to younger patients (P < 0.01). Thus, the LHBT should be assessed carefully in shoulders with more than one RC tear or in chronic cases.

Effects of adipose-derived cell supplementation on tendon-bone healing in a rat model of chronic rotator cuff tear with suprascapular nerve injury.

OBJECTIVE: To investigate the effect of adipose-derived cells (ADCs) on tendon-bone healing in a rat model of chronic rotator cuff tear (RCT) with suprascapular nerve (SN) injury. METHODS: Adult rats underwent right shoulder surgery whereby the supraspinatus was detached, and SN injury was induced. ADCs were cultured from the animals' abdominal fat. At 6 weeks post-surgery, the animals underwent surgical tendon repair; the ADC (+ve) group (n = 18) received an ADC injection, and the ADC (-ve) group (n = 18) received a saline injection. Shoulders were harvested at 10, 14, and 18 weeks and underwent histological, fluorescent, and biomechanical analyses. RESULTS: In the ADC (+ve) group, a firm enthesis, including dense mature fibrocartilage and well-aligned cells, were observed in the bone-tendon junction and fatty infiltration was less than in the ADC (-ve) group. Mean maximum stress and linear stiffness was greater in the ADC (+ve) compared with the ADC (-ve) group at 18 weeks. CONCLUSION: ADC supplementation showed a positive effect on tendon-bone healing in a rat model of chronic RCT with accompanying SN injury. Therefore, ADC injection may possibly accelerate recovery in massive RCT injuries.

Mechanical overload-induced release of extracellular mitochondrial particles from tendon cells leads to inflammation in tendinopathy.

Tendinopathy is one of the most common musculoskeletal diseases, and mechanical overload is considered its primary cause. However, the underlying mechanism through which mechanical overload induces tendinopathy has not been determined. In this study, we identified for the first time that tendon cells can release extracellular mitochondria (ExtraMito) particles, a subtype of medium extracellular particles (mEPs), into the environment through a process regulated by mechanical loading. RNA sequencing systematically revealed that oxygen-related reactions, extracellular particles, and inflammation were present in diseased human tendons, suggesting that these factors play a role in the pathogenesis of tendinopathy. We simulated the disease condition by imposing a 9% strain overload on three-dimensional mouse tendon constructs in our cyclic uniaxial stretching bioreactor. The three-dimensional mouse tendon constructs under normal loading with 6% strain exhibited an extended mitochondrial network, as observed through live-cell confocal laser scanning microscopy. In contrast, mechanical overload led to a fragmented mitochondrial network. Our microscopic and immunoblot results demonstrated that mechanical loading induced tendon cells to release ExtraMito particles. Furthermore, we showed that mEPs released from tendon cells overloaded with a 9% strain (mEP9%) induced macrophage chemotaxis and increased the production of proinflammatory cytokines, including IL-6, CXCL1, and IL-18, from macrophages compared to mEP0%, mEP3%, and mEP6%. Partial depletion of the ExtraMito particles from mEP9% by magnetic-activated cell sorting significantly reduced macrophage chemotaxis. N-acetyl-L-cysteine treatment preserved the mitochondrial network in overloaded tendon cells, diminishing overload-induced macrophage chemotaxis toward mEP9%. These findings revealed a novel mechanism of tendinopathy; in an overloaded environment, ExtraMito particles convey mechanical response signals from tendon cells to the immune microenvironment, culminating in tendinopathy.

No Difference In Clinical Outcomes Following Repair of Large Retracted Anterior Rotator Cuff Tears Using Patch Augmentation With Human Dermal Allograft Versus Anterior Cable Reconstruction With Biceps Tendon Autograft.

PURPOSE: To compare the clinical outcomes and tendon integrity after rotator cuff repair combined with anterior cable reconstruction (ACR) using the proximal biceps tendon and patch augmentation (PA) using a human dermal allograft (HDA) in a large retracted anterior rotator cuff tear. METHODS: Patients who underwent arthroscopic rotator cuff repair with 2 different augmentation procedures between January 2017 and December 2020 were enrolled. The inclusion criteria were patients who were treated by arthroscopic rotator cuff repair with ACR using the proximal biceps tendon (ACR group) or patch augmentation using a an HDA (PA group) and follow-up for at least 2 years. Clinical outcomes were assessed using American Shoulder and Elbow Surgeons (ASES) score, Constant score, and the number of patients who achieved minimal clinically important differences (MCID). Magnetic resonance imaging was performed to evaluate tendon integrity after surgery. RESULTS: A total of 92 patients were enrolled (ACR group = 55 patients and PA group = 37 patients). The mean ASES and Constant scores significantly improved in the ACR group (68.8 ± 15.3 and 58.4 ± 16.9 before surgery vs 91.4 ± 6.3 and 87.8 ± 6.0 after surgery, P < .001) and in the PA group (63.7 ± 16.7 and 57.9 ± 15.4 before surgery vs 93.1 ± 6.3 and 88.3 ± 6.2 after surgery, P < .001). Overall, 78 patients (84.8%) achieved the MCID with 81.8% in the ACR group and 89.2% in the PA group, with no significant differences between the 2 groups (P = .638). Ten patients (18.2%) had retear in the ACR group, and three patients (8.1%) had retear in the PA group (P = .174). CONCLUSIONS: In large retracted anterior rotator cuff tears, both augmentation techniques using biceps tendon autograft and HDA provided satisfactory clinical outcomes that achieved the MCID in 84.8%, range of motion restoration, and lower retear rates with no significant differences between the two groups. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Minimally invasive ultrasound-assisted cutting thread tenotomy of the deep digital flexor tendon in horses: An ex vivo study.

OBJECTIVE: To evaluate the feasibility and limitations associated with a minimally invasive ultrasound-assisted cutting thread technique for tenotomy of the deep digital flexor tendon (DDFT) in horses. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Twenty cadaveric forelimbs. METHODS: Forelimbs were placed on a jig to mimic a standing semiflexed position and the midmetacarpal region was prepared to perform tenotomy of the DDFT using a percutaneous technique with a cutting thread. For that purpose, the thread was placed percutaneously around the DDFT (first dorsally and then palmarly) with the aid of a curved 20 gauge spinal needle. Tendon palpation/manipulation and ultrasonographic assessment assisted thread placement. Procedure time and skin puncture size were recorded. Limbs were then dissected to evaluate the degree of DDFT transection and the presence of any iatrogenic lesions. RESULTS: The DDFT was completely transected in all cases. Minor lesions of the superficial digital flexor tendon were found in 11/20 limbs and considered clinically irrelevant. However, the neurovascular bundle was damaged in 6/20 limbs (four limbs had nerve damage and two limbs had a nerve and either a palmar artery or vein damaged). The skin puncture hole sizes ranged from undetectable to 5 mm long. The average duration of the procedure was 7 min and 38 s (range: 4 min 56 s to 10 min 19 s). CONCLUSION: A DDFT tenotomy can be performed reliably with a percutaneous cutting thread technique. However, refinement of the technique is required to minimize iatrogenic damage. CLINICAL SIGNIFICANCE: The reported technique allows a DDFT tenotomy to be performed in a minimally invasive manner and has the potential to be clinically applicable.

Management of Patellar Tendinopathy.

Patellar tendinopathy is a common pathology typically seen in athletes involved in repetitive explosive jumping and running activities. Also known as jumpers' knee, it is commonly seen in high-level basketball players. Typically, athletes continue to play with symptoms, which can be aggravated and progress to partial patellar tendon tears. When partial patellar tendon tears occur, prolonged recovery and decreased performance is commonly seen. The pathology and treatment can be frustrating for both the athlete and medical provider. Patellar tendinopathy typically does not involve inflammation but rather microinjury to the tendon fibers, which leads to mucoid degeneration, necrosis, and loss of transitional fibrocartilage. When partial tendon tears do occur, the typical location is posteromedially adjacent to the patella. Treatment involves a stepwise approach starting with nonoperative means, including activity modification, nonsteroidal anti-inflammatories, and physical therapy focused on eccentrics. Extracorporeal shock wave treatments and injections with platelet-rich plasma or bone marrow aspirate concentrate should be considered, with evolving literature to support their use. Ultrasound percutaneous tendon scrapping with a needle supplemented with the aforementioned injections is an emerging treatment option that the authors have found to be helpful, although further studies are required. Surgical intervention is considered after failure of nonoperative treatments, and typically occurs in tears greater than 50% of the tendon thickness and in tendons with increased thickness (>8.8 mm). Open or arthroscopic debridement can be considered, with no studies showing superior outcomes with either technique; however, no high-quality comparison studies exist. The authors prefer an open technique where, much like a bone-patellar tendon-bone harvest, the unhealthy proximal tendon and bone are excised with then closure of the healthy tendon with absorbable sutures. Suture anchor repair may also be used when necessary. In a recent systematic review, surgical management of patellar tendinopathy has been shown to result in improved patient-reported outcomes with return to sport at high levels.1 Treatment for the difficult and sometimes frustrating pathology of patellar tendinopathy continues to evolve, with biologic and less-invasive ultrasound-based treatments showing promise, and surgical intervention providing reliable outcomes.

Editorial Commentary: Dasatinib With Quercetin Shows Promise in Decreasing Age-Related Senescence in the Rotator Cuff Tendon-Can It Work Elsewhere?

Cellular senescence is a fundamental mechanism seen in all age-related diseases. Human supraspinatus tendon and adjacent bursal specimens evaluated for cellular senescence by immunohistochemistry and gene expression show more senescent cells in older patients. This confirms the observation that older patients are more likely to have rotator cuff pathology, and older age is associated with lower rates of rotator cuff healing and more frequent tendon retears. Senolytic drugs can selectively eliminate senescent cells without a localized or systemic impact. Tendon and bursal specimens co-cultured and then incubated with dasatinib and quercetin for 48 hours show a significant decrease in senescent cells. This suggests that these drugs may slow biological aging in rotator cuff tendons and offer the possibility of a clinically effective treatment for the aging rotator cuff tendon. Moreover, this concept is promising for the development of future effective therapies addressing tissue senescence.

Shear wave elastography correlates to degeneration and stiffness of the long head of the biceps tendon in patients undergoing tenodesis with arthroscopic shoulder surgery.

BACKGROUND: Tendinopathy of the long head of the biceps (LHB) tendon causes degeneration and changes its stiffness. However, a reliable means of diagnosis has not been established. Shear wave elastography (SWE) provides quantitative tissue elasticity measurements. In this study, the relationship of preoperative SWE values with biomechanically measured stiffness and degeneration of the LHB tendon tissue was investigated. METHODS: LHB tendons were obtained from 18 patients who underwent arthroscopic tenodesis. SWE values were measured preoperatively at 2 sites, proximal to and within the bicipital groove of the LHB tendon. The LHB tendons were detached immediately proximal to the fixed sites and at their superior labrum insertion. Tissue degeneration was histologically quantified using the modified Bonar score. Tendon stiffness was determined using a tensile testing machine. RESULTS: The SWE values of the LHB tendon were 502.1 ± 113.6 kPa proximal to the groove and 439.4 ± 123.3 kPa within the groove. The stiffness was 39.3 ± 19.2 N/mm. The SWE values displayed a moderate positive correlation with the stiffness proximal to the groove (r = 0.80) and within it (r = 0.72). The SWE value of the LHB tendon within the groove showed a moderate negative correlation with the modified Bonar score (r = -0.74). CONCLUSIONS: These findings suggest that preoperative SWE values of the LHB tendon correlate moderately positively with stiffness and moderately negatively with tissue degeneration. Therefore, SWE may predict LHB tendon tissue degeneration and changes in stiffness caused by tendinopathy.

Treatment of Naturally Occurring Tendon Disease with Allogeneic Multipotent Mesenchymal Stromal Cells: A Randomized, Controlled, Triple-Blinded Pilot Study in Horses.

The treatment of tendinopathies with multipotent mesenchymal stromal cells (MSCs) is a promising option in equine and human medicine. However, conclusive clinical evidence is lacking. The purpose of this study was to gain insight into clinical treatment efficacy and to identify suitable outcome measures for larger clinical studies. Fifteen horses with early naturally occurring tendon disease were assigned to intralesional treatment with allogeneic adipose-derived MSCs suspended in serum or with serum alone through block randomization (dosage adapted to lesion size). Clinicians and horse owners remained blinded to the treatment during 12 months (seven horses per group) and 18 months (seven MSC-group and five control-group horses) of follow-up including clinical examinations and diagnostic imaging. Clinical inflammation, lameness, and ultrasonography scores improved more over time in the MSC group. The lameness score difference significantly improved in the MSC group compared with the control group after 6 months. In the MSC group, five out of the seven horses were free of re-injuries and back to training until 12 and 18 months. In the control group, three out of the seven horses were free of re-injuries until 12 months. These results suggest that MSCs are effective for the treatment of early-phase tendon disease and provide a basis for a larger controlled study.

Radiographic evaluation of the bicipital groove morphology does not predict intraarticular changes in the long head of biceps tendon.

INTRODUCTION AND OBJECTIVES: This study aimed to examine the clinical utility of the radiographic evaluation of the bicipital groove in predicting long head of biceps tendon (LHBT) pathology. MATERIAL AND METHODS: A prospective study was conducted, and sixty consecutive patients proposed to shoulder arthroscopic surgery were selected. Before surgery, a radiographic evaluation was performed with a supine and a Fisk radiograph. Most supine radiographs (>75%) were non-interpretable and were excluded from the study. As some Fisk radiographs (26.7%) were also non-interpretable, that left 44 interpretable radiographs in the study. These were measured for medial opening angle, total opening angle, width and depth of the bicipital groove. The radiographic measurements and the presence of LHBT pathology, as assessed at arthroscopy, were correlated. RESULTS: Radiographic evaluation of the bicipital groove showed a mean medial opening angle of 53 ±â€¯15° (23-90), a mean total opening angle of 80 ±â€¯26° (30-135), a mean width of 10.3 ±â€¯2.5 mm (6-19) and a mean depth of 4.1 ±â€¯1.5 mm (1-8). Men had higher medial opening angle (60 vs 50°, p = 0.044) and wider grooves (11.9 vs 9.7 mm, p = 0.019). Twenty-five patients (56.8%) were found to have an abnormal LHBT. No correlation was found between the radiographic measurements and LHBT pathology. Only age was correlated with a LHBT lesion (61.8 vs 46.3 years, p < 0.001). CONCLUSIONS: Our results show that there is no correlation between radiographic morphologic evaluation of the bicipital groove and LHBT pathology.

A Mass on the Sole Revealing a Giant-Cell Tumor of the Tendon Sheath.

A 61-year-old woman presented with a 3-year history of painless soft-tissue mass on the right sole. The patient reported gradual growth, with a rapid increase in size over the past few months, leading to difficulty in walking. She had no history of past trauma. Examination revealed a 4-cm ovoid mass located over the ball of the foot. It was firm in consistency, with well-defined margins, a smooth surface, and an overlying normal skin (Figure 1). An ultrasound image revealed an eccentric, hypoechoic, nonvascular subcutaneous lobular mass. A magnetic resonance imaging (MRI) of the foot revealed a well-defined mass arising from the flexor tendon sheath of the right foot. The lesion was heterogeneously hyperin-tense on T1- and T2-weighted images with an avid contrast enhancement. All of the surrounding soft tissues indicated normal signal intensity patterns. There was no associated bony destruction. Histopathologic examination after complete excision of the mass established a well-circumscribed lesion composed of osteoclast-like giant cells and mononuclear cells in a hyalinized stroma, consistent with a giant cell tumor of the tendon sheath (GCT-TS) (Figure 2). There was no recurrence during a 6-month follow-up period (Figure 3).

Perivascular wall tumour presenting as pastern mass in a Standardbred gelding.

A 2-year-old Standardbred gelding was referred for a mass on the palmaromedial right front pastern which was accompanied by progressively worsening lameness. The mass was firm to palpation and covered by normal skin. Ultrasonographically, a smooth encapsulated mass was present, medial to the flexor tendons and palmar to the neurovascular bundle. Because of a poor prognosis for future athletic performance without surgical or chemotherapeutic intervention and economic constraints preventing further diagnostics and treatment, the horse was euthanised. Post-mortem magnetic resonance imaging, histopathology and immunohistochemistry revealed the mass to be a perivascular wall tumour, the first record of such a neoplasia in the horse.

Cytomorphologic panorama of giant cell tumour of tendon sheath.

BACKGROUND: Giant Cell Tumour of Tendon Sheath (GCTTS) is a slow growing benign soft tissue tumour arising from synovium of tendon sheath or joint. These tumours occur more frequently in upper limbs, especially hands. In the present study, we aimed to evaluate the cytomorphological spectrum of GCTTS. METHODS: This retrospective study includes a total of 56 cases of GCTTS diagnosed over a period of 8 years. The clinical and radiological details of these cases were retrieved from the cytopathology records and detailed cytomorphological features were studied and analysed. Histopathological correlation was done in 16/56 cases, where follow-up was available. RESULTS: The mean age of patients at the time of presentation was 32 years and were predominantly females (68%). The most common site of GCTTS was fingers (76%), followed by foot, wrist and toes. The most consistent finding on cytology was stromal cells (100%) of polygonal, spindle and plasmacytoid morphology with interspersed multinucleated osteoclastic giant cells (100%), followed by binucleated stromal cells (75%), xanthoma cells (61%) and hemosiderin laden macrophages (52%). Presence of proteinaceous fluid background was also observed in 50% of the cases. CONCLUSION: GCTTS can be diagnosed with certainty on FNAC based on characteristic cytomorphological features in an appropriate clinical and radiological setting. FNAC plays a pivotal role in diagnosing GCTTS and differentiating it from other giant cell rich lesions, thus obviating the need of tissue biopsy for diagnosis, which in turn helps the clinician in timely and adequate management of the patient.

Giant Cell Tumour of Tendon Sheath of Distal Phalanx of Thumb: A Case Report.

Giant cell tumour of tendon sheath is an uncommon benign soft tissue tumour. Histopathological examination plays a crucial role in the definitive diagnosis of giant cell tumour although pre-operative imaging supports its suspicion. We report a case of a giant cell tumour of the tendon sheath in a 26-year-old man as a painless, firm, localized, slow-growing benign soft tissue tumour of the thumb; managed by complete excision. The patient continues to do well at 7 months post-surgery with no complaints and no signs of recurrence. Giant cell tumour of the phalanges is a locally aggressive entity; therefore delayed or missed diagnosis of giant cell tumour especially of the thumb distal phalanx can be extremely debilitating. Hence, high degree of suspicion and early en bloc resection is the key to its management. Keywords: case reports; giant cell tumors; tendons; thumb.

Gender and degree of tendon healing are independent predictive factors for clinical outcome in successfully healed rotator cuff tears.

PURPOSE: Arthroscopic rotator cuff repair (aRCR) is a commonly performed procedure and has been reported to be a successful treatment. Successful healing has traditionally been considered to be associated with good outcome; however, knowledge on predictive factors affecting final outcome other than tendon healing is limited. This study aims to investigate predictive factors influencing clinical outcome following aRCR in patients with successfully healed tears. METHODS: This retrospective case-control study was conducted in a single center with 135 patients who had successfully healed tendons based on Sugaya classification (grades I-III) on postoperative magnetic resonance imaging (MRI) scans following aRCR. Clinical outcome measures included Constant-Murley score (CMS), range of motion (ROM), pain score. Various preoperative, intraoperative factors and degree of postoperative tendon healing were assessed to identify independent predictive factors for final clinical outcome. RESULTS: Mean age of patients was 55.9 ± 9.0 years and mean follow-up duration was 46.8 ± 14.9 months. There were 50 (37%) male and 85 (63.0%) female patients. At final follow-up, mean CMS was 85.7 ± 12.0. Considering mean postoperative CMS and the minimal clinically important difference (MCID) of 10 points for CMS, a cutoff level of 75 points for CMS was set (85-10 = 75) and study population was divided into two study groups (group I, poor outcome, CMS ≤ ;75, and group II, good outcome, CMS > 75). There were 24 (17.8%) patients in group I and 111 (82.2%) patients in group II. Univariate analysis revealed that gender, body mass index (BMI) and degree of tendon healing (Sugaya classification) differed significantly between two groups (p < 0.05). Multivariate logistic regression analysis which was conducted with these variables showed that female gender (odds ratio 3.65) and Sugaya grade III (odds ratio 8.19) were independent predictive factors which were significantly associated with poor outcome (p < 0.05). CONCLUSIONS: This study showed that despite achieving a successful healing, considerable amount of patients (17.8%) have ended up with poor outcome. Female gender and degree of tendon healing were identified as independent predictive factors for poor outcome. These data would help surgeons during decision-making, risk assessment and patient counseling. LEVEL OF EVIDENCE: III.

Can pirfenidone prevent tendon adhesions? An experimental study in rats.

OBJECTIVES: In this experimental study, we aimed to investigate the effectiveness of oral pirfenidone (PFD) treatment on preventing tendon adhesion and tendon healing in rats. MATERIALS AND METHODS: A total of 21 rats were assigned into three groups including seven rats in each group. In Group 1 (sham group), no surgical procedure was performed. In Group 2 (control group), tendon repair was performed following right achillotomy. In Group 3 (treatment group), the rats also underwent tendon repair after right achillotomy. Additionally, 30 mg/kg of oral PFD was initiated from the postoperative Day 1 and administered via gavage for 28 days. At the end of the study, tendon healing and fibrosis levels in the tendon repair site were compared macroscopically, histopathologically, and immunohistochemically among the groups. RESULTS: Macroscopically, moderate and severe adhesions were observed in four and three rats, respectively in the control group, while no adhesion was found in four rats and filmy adhesions were observed in three rats in the treatment group (p<0.01). Microscopically, there was moderate adhesions in three rats and severe adhesions in four rats in the control group, while three rats had no adhesions and four rats had slight adhesions in the treatment group (p<0.01). Microscopically, tendon healing was good in six rats and fair in one rat in the control group, while five rats showed excellent tendon healing and two rats showed good tendon healing in the treatment group (p<0.01). Immunohistochemically, expressions of collagen I (p<0.01), collagen III (p<0.001), vascular endothelial growth factor (VEGF) (p<0.001), and proliferating cell nuclear antigen (PCNA) (p<0.001) significantly decreased in the treatment group compared to the control group. CONCLUSION: Our study results indicated that PFD decreased collagen synthesis and prevented the formation of peritendinous adhesion in rats; however, it did not impair tendon healing.

Methods to analyse the long head of the biceps in the management of distal ruptures of the supraspinatus tendon. Part 1: the concept of the "biceps box": dynamic rotator interval approach. Incidence of lesions of the long head of the biceps tendon.

INTRODUCTION: The area encompassing the long head of the biceps (LHB) can be represented as a rectangular parallelepiped. This geometric view can be likened to a box, the "biceps box", where the sides are the extrinsic structures and the LHB is the intrinsic structure. Since these structures are mobile in relation to each other, a dynamic "biceps box" model can modify assessments of the LHB, in its healthy or pathological state, and make the therapeutic approach to treating LHB lesions less arbitrary. MATERIAL AND METHOD: In order to describe the different sides of the "biceps box", and to understand their possible physiological and pathological consequences, a literature review using PRISMA methodology was used. RESULTS: The supraspinatus (SSP) has expansions on its anterior aspect that project anteriorly and cross the coracohumeral ligament (CHL). The most functionally important expansion is the fasciculus obliquus, which extends perpendicular to the axis of the tendon fibers of the SSP, divides the CHL into a deep and a superficial layer, and terminates on the superficial aspect of the subscapularis. The humeral insertion of the SSP may be binary, making a bridge over the LHB, with a posterior branch inserting on the greater tuberosity and an anterior branch on the lesser tuberosity. The superior glenohumeral ligament (SGHL) has a twisted course, downward and forward, and ends at the proximal opening of the bicipital groove with a flap on which the LHB rests. The bicipital pulley is not an independent structure but an arciform structure resulting from the fusion of several tissues. DISCUSSION: The presence of structures linked together by common expansions in the 3 planes of space validates the relevance of a "biceps box" as a functional geometric model. The structure that acts as a crossroads through which all expansions pass is the CHL. An extrinsic SSP lesion can be compensated for by other "biceps box" structures, whereas an extrinsic SGHL lesion rarely exists without the presence of an intrinsic LHB lesion. The CHL constitutes a connective tissue crossed by a vasculonervous pedicle from the lateral pectoral nerve, which may explain some anterior shoulder pain attributed to the biceps. CONCLUSION: The LHB can be likened to an intrinsic structure contained in a box whose sides are made up of different interconnected stabilizing structures defining the extrinsic structures. The concept of a dynamic "biceps box" allows LHB lesions to be accurately classified, separating extrinsic and intrinsic lesions, and thus potentially modifying therapeutic approaches to the LHB. LEVEL OF EVIDENCE: IV; systematic review.