Increased Ca2+ signaling through CaV 1.2 induces tendon hypertrophy with increased collagen fibrillogenesis and biomechanical properties.

Tendons are tension-bearing tissues transmitting force from muscle to bone for body movement. This mechanical loading is essential for tendon development, homeostasis, and healing after injury. While Ca2+ signaling has been studied extensively for its roles in mechanotransduction, regulating muscle, bone, and cartilage development and homeostasis, knowledge about Ca2+ signaling and the source of Ca2+ signals in tendon fibroblast biology are largely unknown. Here, we investigated the function of Ca2+ signaling through CaV 1.2 voltage-gated Ca2+ channel in tendon formation. Using a reporter mouse, we found that CaV 1.2 is highly expressed in tendon during development and downregulated in adult homeostasis. To assess its function, we generated ScxCre;CaV 1.2TS mice that express a gain-of-function mutant CaV 1.2 in tendon. We found that mutant tendons were hypertrophic, with more tendon fibroblasts but decreased cell density. TEM analyses demonstrated increased collagen fibrillogenesis in the hypertrophic tendons. Biomechanical testing revealed that the hypertrophic tendons display higher peak load and stiffness, with no changes in peak stress and elastic modulus. Proteomic analysis showed no significant difference in the abundance of type I and III collagens, but mutant tendons had about two-fold increase in other ECM proteins such as tenascin C, tenomodulin, periostin, type XIV and type VIII collagens, around 11-fold increase in the growth factor myostatin, and significant elevation of matrix remodeling proteins including Mmp14, Mmp2, and cathepsin K. Taken together, these data highlight roles for increased Ca2+ signaling through CaV 1.2 on regulating expression of myostatin growth factor and ECM proteins for tendon collagen fibrillogenesis during tendon formation.

Experts Achieve Consensus on a Majority of Statements Regarding Platelet-Rich Plasma Treatments for Treatment of Musculoskeletal Pathology.

PURPOSE: To establish consensus statements on platelet-rich plasma (PRP) for the treatment of musculoskeletal pathologies. METHODS: A consensus process on the treatment of PRP using a modified Delphi technique was conducted. Thirty-five orthopaedic surgeons and sports medicine physicians participated in these consensus statements on PRP. The participants were composed of representatives of the Biologic Association, representing 9 international orthopaedic and musculoskeletal professional societies invited due to their active interest in the study of orthobiologics. Consensus was defined as achieving 80% to 89% agreement, strong consensus was defined as 90% to 99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: There was consensus on 62% of statements about PRP. CONCLUSIONS: (1) PRP should be classified based on platelet count, leukocyte count, red blood count, activation method, and pure-plasma versus fibrin matrix; (2) PRP characteristics for reporting in research studies are platelet count, leukocyte count, neutrophil count, red blood cell count, total volume, the volume of injection, delivery method, and the number of injections; (3) the prognostic factors for those undergoing PRP injections are age, body mass index, severity/grade of pathology, chronicity of pathology, prior injections and response, primary diagnosis (primary vs postsurgery vs post-trauma vs psoriatic), comorbidities, and smoking; (4) regarding age and body mass index, there is no minimum or maximum, but clinical judgment should be used at extremes of either; (5) the ideal dose of PRP is undetermined; and (6) the minimal volume required is unclear and may depend on the pathology. LEVEL OF EVIDENCE: Level V, expert opinion.

Meniscus Extrusion, Radial Tears, and Root Tears.

Management of meniscal radial and root tears and extrusion is complex and has changed significantly over recent years. It is important to provide a comprehensive overview of the management of radial and root tears and meniscal extrusion and be aware of the currently available evidence on repair techniques, rehabilitation, and outcomes following radial and root repairs.

Bilateral glenohumeral internal rotation deficit (GIRD) in elite gymnasts.

INTRODUCTION: The "Glenohumeral Internal Rotation Deficit (GIRD)" is known as the difference in internal rotation range of motion (IRRM) between the dominant and non-dominant shoulder of overhead athletes as a result of asymmetric loading. As in contrast loading pattern in gymnastics are quite symmetric and structural changes often occur bilaterally, the question arises if GIRD might develop bilaterally in gymnasts as one source of common bilateral shoulder pathologies and to search for underlying structural adaptations. MATERIALS AND METHODS: A group of 35 elite gymnasts (8-24 years) were recruited from a local Olympic Training Centre and compared to a paired cohort of 28 non-overhead athletes. Clinical examinations, digital range of motion (ROM)-measurement, ultrasonographic humeral torsion measurement, and standardized MRI scans of both shoulders were obtained and examined for structural pathologies, cross-sectional areas (CSA) of the rotator cuff muscles and capsular thickness. RESULTS: ROM-measurements showed significant decrease in IRRM in the gymnasts groups by age, with IRRM of 48.6° (SD: 8.4°, CI 95%: 43.0-54.3°) at age group 1 (8-10 years) and IRRM of 10° (SD: 11.4°; CI 95%: 0-22.0°) at age group 4 (18-26 years), that was statistically significant for the entire cohort (p = 0.017) compared to the controls. CSA were not significantly different between the cohorts, while there was a slightly increased humeral retrotorsion in the gymnasts as well as a statistically significant posterior capsular thickening. CONCLUSION: A new bilateral form of GIRD was identified in higher age groups of youth and senior elite gymnasts enrolled in this study. Despite to former definition of GIRD there was no compensatory increase in external rotation range of motion (ERRM) but an association with posterior capsular thickening, while there was no periscapular muscle hypertrophy. Humeral retrotorsion was also slightly increased in the gymnasts group.

Evaluating the role of subacromial impingement in rotator cuff tendinopathy: development and analysis of a novel rat model.

BACKGROUND: Subacromial impingement of the rotator cuff caused by variations in acromial anatomy or altered glenohumeral kinematics leads to inflammation and degeneration of the rotator cuff, ultimately contributing to the development of tendinopathy. However, the underlying cellular and molecular changes in the impinged tendon remain poorly understood. Because the rat is an accepted model for rotator cuff studies, we have developed a rat model to study rotator cuff tendinopathy. METHODS: Forty-four adult male Sprague-Dawley rats were allocated to one of 4 study groups: intact control group (group 1, n = 11); bilateral subacromial surgical clip placement to induce supraspinatus impingement for 2 weeks (group 2, n = 11), 4 weeks (group 3, n = 11), and 8 weeks (group 4, n = 11). Bilateral shoulder specimens were harvested for biomechanical testing, histology, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RESULTS: Radiography confirmed that all microvascular clips remained in stable position in the subacromial space. Gross inspection of supraspinatus tendon specimens in the impingement groups revealed changes in tendon morphology at the enthesis and midsubstance. Biomechanical evaluation demonstrated decreased supraspinatus tendon failure force and tissue stiffness at all time points compared with control tendons. Semiquantitative scoring of histologic specimens demonstrated significant, persistent tendinopathic changes over 8 weeks. qRT-PCR analysis of impinged tendon specimens demonstrated upregulation of gene expression for Col3 and Mmp14 in the impingement groups compared with control groups. In muscle samples, significant upregulation was seen in the expression of genes that are commonly associated with muscle atrophy (MuRF1 and Ube2b) and fatty infiltration (Fabp4, Pparg2, and Klf15). CONCLUSION: This new rat subacromial impingement model creates cellular and molecular changes consistent with the development of rotator cuff tendinopathy. The results of this study may serve as a baseline for future investigation.

Subacromial bursa increases the failure force in a mouse model of supraspinatus detachment and repair.

BACKGROUND: It has been shown that subacromial bursa (SAB) harbors connective tissue progenitor cells. The purpose of this study was to evaluate the effects of implantation of SAB-derived cells (SBCs) suspended in a fibrin sealant bead and implantation of SAB tissue at rotator cuff repair site on biomechanical properties of the repair in a mouse (C57Bl/6) model of supraspinatus tendon (ST) detachment and repair. METHODS: Part 1: Murine SAB tissue was harvested and cultured. Viability of SBCs suspended in 10 µL of fibrin sealant beads was confirmed in vitro and in vivo. Eighty mice underwent right ST detachment and repair augmented with either fibrin sealant bead (control group) or fibrin sealant bead with 100,000 SBCs (study group) applied at the repair site. Part 2: 120 mice underwent right ST detachment and repair and were randomized equally into 4 groups: (1) a tissue group, which received a piece of freshly harvested SAB tissue; (2) a cell group, which received SBCs suspended in fibrin sealant bead; (3) a fibrin sealant group, which received plain fibrin sealant bead without cells; and (4) a control group, which received nothing at the ST repair site. An equal number of mice in each group were killed at 2 and 4 weeks. Specimens underwent biomechanical testing to evaluate failure force (part 1 and 2) and histologic analysis of the repair site (part 1 only). RESULTS: Part 1: The mean failure force in the study group was significantly higher than controls at 2 and 4 weeks (3.25 ± 1.03 N vs. 2.43 ± 0.56 N, P = .01, and 4.08 ± 0.99 N vs. 3.02 ± 0.8 N, P = .004, respectively). Mean cell density of the ST at the repair site was significantly lower in the study group at 2 weeks than in controls (18,292.13 ± 1706.41 vs. 29,501.90 ± 3627.49, P = .001). Study group specimens had lower proteoglycan contents than controls, but this difference was not statistically significant. Part 2: There was no difference in failure force between cell and tissue groups at the 2- and 4-week time points (P = .994 and P = .603, respectively). There was no difference in failure force between fibrin sealant bead and control groups at the 2- and 4-week time points (P = .978 and P = .752, respectively). CONCLUSION: This study shows that the application of SBCs and SAB tissue at the rotator cuff repair site increases the strength of repair in a murine model of rotator cuff detachment and repair.

Biomechanical analysis of anterior stability after 15% glenoid bone loss: comparison of Bankart repair, dynamic anterior stabilization, dynamic anterior stabilization with Bankart repair, and Latarjet.

BACKGROUND: Dynamic anterior shoulder stabilization (DAS) with Bankart repair is a recently described stabilization technique thought to be more robust than an isolated Bankart repair while avoiding many coracoid transfer-related complications and technical demands. DAS involves transfer of the long head biceps through a subscapularis split to the anterior glenoid to create a sling effect. We hypothesize that DAS with Bankart repair will restore anterior stability in a human-cadaveric model with subcritical (15%) glenoid bone loss. METHODS: Eight cadaveric shoulders were tested using an established shoulder simulator to record glenohumeral translations with an accuracy of ±0.2 mm. Shoulders were tested in 5 states-intact soft tissues, Bankart defect with 15% bone loss, isolated Bankart repair, DAS with Bankart repair, isolated DAS, and Latarjet. A 45 N anterior force was applied through the pectoralis major tendon, and translation of the humeral head was recorded and compared with repeated measures analysis of variance. RESULTS: The anterior translation in the intact (native) glenoid was 4.7 mm at neutral position and 4.6 mm at 45° external rotation. Anterior translation significantly increased after introducing a Bankart defect with 15% glenoid bone loss to 9.1 mm (neutral, P = .002) and 9.5 mm (45° external rotation, P < .001). All repair conditions showed a significant decrease in anterior translation relative to Bankart defect. DAS with Bankart repair decreased anterior translation compared with the Bankart defect: 2.7 mm (neutral, P < .001) and 2.1 mm (45° external rotation, P < .001). DAS with Bankart repair significantly decreased anterior translation compared with the isolated Bankart repair (2.7 mm vs. 4.7 mm, P = .023) and the isolated DAS (2.7 mm vs. 4.3 mm, P = .041) in neutral position. The Latarjet procedure resulted in the greatest reduction in anterior translation compared with the Bankart defect: 1.2 mm (neutral, P < .001) and 1.9 mm (45° external rotation, P < .001). CONCLUSIONS: DAS with Bankart repair is a viable alternative to restore anterior glenohumeral stability with a 15% glenoid defect at a greater degree than either DAS or Bankart repair alone. The Latarjet procedure was the most effective in reducing anterior translation but restrained the anterior translation significantly more than the native glenoid.

Minimum 15-year follow-up for clinical outcomes of arthroscopic rotator cuff repair.

BACKGROUND AND HYPOTHESIS: Arthroscopic rotator cuff repair surgery is one of the most common shoulder procedures performed in the United States. Although several studies have shown considerable symptomatic relief in the short term following surgery, a relatively high rate of recurrent defects has led surgeons to question the long-term durability of this operation. We hypothesized that outcomes at a minimum of 15 years of follow-up in patients who underwent all-arthroscopic rotator cuff repair would be maintained and would remain significantly improved compared with the preoperative status. METHODS: All-arthroscopic rotator cuff repairs were performed in 193 patients from 2003 to 2005. Patient-reported outcomes were collected preoperatively and at 1, 2, 5, and ≥15 years postoperatively. The primary outcome was the American Shoulder and Elbow Surgeons (ASES) score. Secondary outcomes included Single Assessment Numeric Evaluation (SANE), Shoulder Activity Scale (SAS), visual analog scale, and Patient-Reported Outcomes Measurement Information System (PROMIS)-Upper Extremity (UE) scores. Patient demographic characteristics, revision surgical procedures, and complications were recorded. Generalized estimating equations were used to model scores over time, and multiple comparisons between time points were performed using Tukey adjustment. RESULTS: This study included 60 patients with a mean follow-up period of 16.5 years (range, 15.8-17.7 years). The mean ASES score improved from 60.2 ± 18.8 preoperatively to 93.0 ± 9.4 at ≥15 years (P < .0001). The mean visual analog scale pain score decreased from 4.1 ± 0.7 preoperatively to 0.7 ± 0.3 at ≥15 years (P < .0001). The average SANE, SAS, and PROMIS-UE scores at ≥15 years were 87.8 ± 14.8, 8.8 ± 4.3, and 49.6 ± 10.2, respectively. Of 60 patients, 7 underwent revision surgery. Older age and female sex were associated with lower SAS scores at 15 years, whereas female sex was associated with lower PROMIS-UE scores. There were no factors predictive of ASES or SANE scores. CONCLUSION: At long-term follow-up (≥15 years), the patient-reported outcomes of all-arthroscopic rotator cuff repair show significant improvement from baseline preoperative function and remain durable over a period of 15 years. This information is useful in counseling patients regarding the long-term results of this procedure.

Editorial Commentary: Cell-Based Therapies for Articular Cartilage Repair Require Precise Progenitor Cell Characterization and Determination of Mechanism of Action.

Biologics and cell-based therapies, in particular, have come to the forefront of orthopaedic sports medicine as agents with therapeutic and regenerative potential. Autologous chondrocyte implantation has been used successfully for many years, but a recent focus on autologous progenitor cells derived from bone marrow aspirate, adipose tissue, and/or synovium has garnered significant interest. Mobilized peripheral blood mononuclear cells [PBMCs or connective tissue progenitors (CTPs)] represent a promising cell population for potential use in articular cartilage repair. The term "stem cell" has become widely popularized, but more specific language identifying the cell type by donor type, tissue of origin, cell surface marker profile, culture conditions, and other cell behavior/characteristics should be used. In 2019, Murray et al. proposed a five-item "DOSES" tool in an effort to encourage standardized reporting for cell-based therapies emphasizing donor, origin of tissue, separation from other cell types/preparation method, exhibited cell characteristics associated with behavior, and site of delivery. The advantages of the DOSES tool include both simplicity and ability to be applied to cell types not yet discovered. However, a universally accepted list of criteria for biologics does not yet exist. Additional research is necessary to better elucidate the precise mechanisms by which cell therapies have a clinical effect and define whether the therapies for the treatment of cartilage pathology merely help alleviate symptoms or actually provide structural improvements. There are few data to suggest exogenous cell therapies directly engraft, so identifying the paracrine mediators produced by these cells would be an area of further interest.

Effect of Vancomycin Soaking on Anterior Cruciate Ligament Graft Biomechanics.

PURPOSE: To evaluate the effect of soaking of anterior cruciate ligament (ACL) grafts in vancomycin solution on graft biomechanical properties at the time of implantation. METHODS: The central third of patellar tendons was harvested from mature bovine knees and prepared as a tendon-only graft or a bone-tendon-bone (BTB) graft. Tendons were wrapped in gauze soaked in vancomycin solution (VS) (5 mg/mL) or normal saline (NS) and left to stand for 30 minutes at room temperature, simulating graft exposure times in the operating room during ACL reconstruction. Tensile testing was carried out on a materials testing system with (1) low-magnitude loading (60 N at 3 mm/s) with repeated testing of tendon-only grafts; and (2) high-magnitude loading (600 N at 10 mm/min) of BTB grafts. For tendon-only grafts, specimens were first wrapped in NS-soaked gauze and underwent testing, with repeated testing performed after wrapping in gauze soaked in VS or buffered VS (pH 7.0). For BTB grafts, specimens were randomly assigned to treatment with VS or NS. RESULTS: For tendon-only grafts, there was no difference in Young's modulus (YM) after soaking with VS soaking (baseline, 12.69 MPa; treatment, 16.07 ± 4.44 MPa; P = .99) or buffered VS (baseline, 12.45 ± 4.55 MPa; treatment, 15.56 ± 2.83 MPa; P = .99). For BTB grafts, there were no differences in elongation strain (VS, 46.8% ± 7.0%; NS, 31.5% ± 13.5%, P = .19) or YM (VS, 158.4 ± 15.8 MPa; NS, 158.5 ± 23.3 MPa, P = .99). CONCLUSIONS: According to controlled biomechanical tests, vancomycin soaking of patellar tendon grafts does not adversely affect time-zero material properties. CLINICAL RELEVANCE: This study suggests that vancomycin wrapping has no immediate adverse effects on the biomechanical properties of ACL grafts. Randomized controlled trials are warranted to validate the widespread use of vancomycin soaking of tendon grafts for infection prophylaxis during ACL reconstruction.

Computed Tomography-Based Preoperative Planning Provides a Pathology and Morphology-Specific Approach to Glenohumeral Instability With Bone Loss.

PURPOSE: To use computed tomography (CT) to determine a reproducible method of coracoid measurement to compare the ability of the classic Latarjet technique and the congruent arc modification (CAM) to restore native glenoid diameter and to develop a preoperative planning algorithm for glenoid restoration with a goal of achieving an on-track shoulder. METHODS: Coracoid dimensions were measured on multiplanar reconstructed shoulder CT scans of patients aged 18 to 45 years obtained between December 1, 2019, and March 13, 2020. Patients were excluded if CT demonstrated osteophyte formation, glenoid dysplasia, coracoid fracture, or tumor. The proportion of glenoid diameter able to be restored using classic Latarjet technique and CAM were calculated. A treatment algorithm was proposed considering the amount of bone loss present and coracoid dimensions. RESULTS: Coracoid dimensions of 117 consecutive patients were measured and varied considerably (length: 17.5-31.8 mm, width: 9.1-20.5 mm, thickness: 6.1-15.7 mm). While most patients had harvestable coracoid length ≥20 mm (male: 96.3% vs female: 94.4%, P = .65), only 27.8% of female patients had coracoid thickness ≥10 mm. When comparing Latarjet techniques, there was no difference in the proportion of patients in whom 30% glenoid diameter could be fully restored, but CAM was able to restore at least 35% in more male and female patients (98.8% vs 79.0% and 100% vs 61.1%, respectively, P = .00001). Intra- and inter-rater reliability was excellent ( intraclass correlation coefficient ≥0.950 for all dimensions). CONCLUSIONS: We describe a reliable method of measuring coracoid dimensions for preoperative planning of glenoid restoration. The classic Latarjet technique reliably restores the glenoid anteroposterior diameter with bone loss of up to 30%. The majority of female patients have coracoid thickness <10 mm, which may increase the risk of graft fracture when using CAM. The decision to use the classic Latarjet technique or CAM considers each individual's glenoid and coracoid dimensions with a goal of achieving an on-track shoulder. CLINICAL RELEVANCE: Our reliable method of coracoid measurement demonstrated the differing abilities of the classic Latarjet and CAM to restore the native glenoid diameter. An evidence-based algorithm using these measurements was developed to assist in preoperative planning for glenohumeral instability in the setting of bone loss, with a goal of achieving an on-track shoulder. Alternative techniques may be considered if an on-track shoulder cannot be achieved with Latarjet.

Complications Following Biologic Therapeutic Injections: A Multicenter Case Series.

PURPOSE: To describe the complications that occur following biologic therapeutic injections. METHODS: We queried physician members of the Biologic Association, a multidisciplinary organization dedicated to providing a unified voice for all matters related to musculoskeletal biologics and regenerative medicine. Patients included in this study must have (1) received a biologic injection, (2) sustained an adverse reaction, and (3) had a minimum of 1-year follow-up after the injection. Patient demographic information, medical comorbidities, diagnoses, and previous treatments were recorded. The type of injection, injection setting, injection manufacturers, and specific details about the complication and outcome were collected. RESULTS: In total, 14 patients were identified across 6 institutions in the United States (mean age 63 years, range: 36-83 years). The most common injections in this series were intra-articular knee injections (50%), followed intra-articular shoulder injections (21.4%). The most common underlying diagnosis was osteoarthritis (78.5%). Types of injections included umbilical cord blood, platelet-rich plasma, bone marrow aspirate concentrate, placental tissue, and unspecified "stem cell" injections. Complications included infection (50%), suspected sterile inflammatory response (42.9%), and a combination of both (7.1%). The most common pathogen identified from infection cases was Escherichia coli (n = 4). All patients who had isolated infections underwent treatment with at least one subsequent surgical intervention (mean: 3.6, range: 1-12) and intravenous antibiotic therapy. CONCLUSIONS: This study demonstrates that serious complications can occur following treatment with biologic injections, including infections requiring multiple surgical procedures and inflammatory reactions. LEVEL OF EVIDENCE: Level IV, case series.

Arthroscopic-Assisted Coracoclavicular Ligament Reconstruction: Clinical Outcomes and Return to Activity at Mean 6-Year Follow-Up.

PURPOSE: To report clinical and functional outcomes including return to preinjury activity level following arthroscopic-assisted coracoclavicular (CC) ligament reconstruction (AA-CCR) and to determine associations between return to preinjury activity level, radiographic outcomes, and patient-reported outcomes following AA-CCR. METHODS: A institutional registry review of all AA-CCR using free tendon grafts from 2007 to 2016 was performed. Clinical assessment included Single Assessment Numeric Evaluation (SANE) score and return to preinjury activity level at final follow-up. Treatment failure was defined as (1) revision acromioclavicular stabilization surgery, (2) unable to return to preinjury activity level, or (3) radiographic loss of reduction (RLOR, >25% CC distance compared with contralateral side). SANE scores, return to activity, and RLOR were compared between patients within each category of treatment failure, by grade of injury, and whether concomitant pathology was treated. RESULTS: There were 88 patients (89.8% male) with mean age of 39.6 years and minimum 2-year clinical follow-up (mean 6.1 years). Most injuries were Rockwood grade V (63.6%). Mean postoperative SANE score was 86.3 ± 17.5. Treatment failure occurred in 17.1%: 8.0% were unable to return to activity, 5.7% had RLOR, and 3.4% underwent revision surgery due to traumatic reinjury. SANE score was lower among patients who were unable to return to activity compared with those with RLOR and compared with nonfailures (P = .0002). There were no differences in revision surgery rates, return to activity, or SANE scores according to Rockwood grade or if concomitant pathology was treated. CONCLUSIONS: AA-CCR with free tendon grafts resulted in good clinical outcomes and a high rate of return to preinjury activity level. RLOR did not correlate with return to preinjury activity level. Concomitant pathology that required treatment did not adversely affect outcomes. Return to preinjury activity level may be a more clinically relevant outcome measure than radiographic maintenance of acromioclavicular joint reduction. LEVEL OF EVIDENCE: IV (Case Series).

Mesenchymal stromal cells and platelet-rich plasma promote tendon allograft healing in ovine anterior cruciate ligament reconstruction.

PURPOSE: The effect of bone marrow mesenchymal stromal cells (BMSCs) and platelet-rich plasma (PRP) on tendon allograft maturation in a large animal anterior cruciate ligament (ACL) reconstruction model was reported for the first time. It was hypothesised that compared with non-augmented ACL reconstruction, BMSCs and PRP would enhance graft maturation after 12 weeks and this would be detected using magnetic resonance imaging (MRI). METHODS: Fifteen sheep underwent unilateral tendon allograft ACL reconstruction using aperture fixation and were randomised into three groups (n = 5). Group 1 received 10 million allogeneic BMSCs in 2 ml fibrin sealant; Group 2 received 12 ml PRP in a plasma clot injected into the graft and bone tunnels; and Group 3 (control) received no adjunctive treatment. At autopsy at 12 weeks, a graft maturation score was determined by the sum for graft integrity, synovial coverage and vascularisation, graft thickness and apparent tension, and synovial sealing at tunnel apertures. MRI analysis (n = 2 animals per group) of the signal-noise quotient (SNQ) and fibrous interzone (FIZ) was used to evaluate intra-articular graft maturation and tendon-bone healing, respectively. Spearman's rank correlation coefficient (r) of SNQ, autopsy graft maturation score and bone tunnel diameter were analysed. RESULTS: The BMSC group (p = 0.01) and PRP group (p = 0.03) had a significantly higher graft maturation score compared with the control group. The BMSC group scored significantly higher for synovial sealing at tunnel apertures (p = 0.03) compared with the control group. The graft maturation score at autopsy significantly correlated with the SNQ (r = - 0.83, p < 0.01). The tunnel diameter of the femoral tunnel at the aperture (r = 0.883, p = 0.03) and mid-portion (r = 0.941, p = 0.02) positively correlated with the SNQ. CONCLUSIONS: BMSCs and PRP significantly enhanced graft maturation, which indicates that orthobiologics can accelerate the biologic events in tendon allograft incorporation. Femoral tunnel expansion significantly correlated with inferior maturation of the intra-articular graft. The clinical relevance of this study is that BMSCs and PRP enhance allograft healing in a translational model, and biological modulation of graft healing can be evaluated non-invasively using MRI.

The glenohumeral ligaments: Superior, middle, and inferior: Anatomy, biomechanics, injury, and diagnosis.

The three glenohumeral ligaments (superior, middle, and inferior) are discrete thickenings of the glenohumeral joint capsule and are critical to shoulder stability and function. Injuries to this area are a cause of significant musculoskeletal morbidity. A literature search was performed by a review of PubMed, Google Scholar, and OVID for all relevant articles published up until 2020. This study highlights the anatomy, biomechanical function, and injury patterns of the glenohumeral ligaments, which may be relevant to clinical presentation and diagnosis. A detailed understanding of the normal anatomy and biomechanics is a necessary prerequisite to understanding the injury patterns and clinical presentations of disorders involving the glenohumeral ligaments of the shoulder.

Widespread diversity in the transcriptomes of functionally divergent limb tendons.

KEY POINTS: Tendon is a hypocellular, matrix-rich tissue that has been excluded from comparative transcriptional atlases. These atlases have provided important knowledge about biological heterogeneity between tissues, and our study addresses this important gap. We performed measures on four of the most studied tendons, the Achilles, forepaw flexor, patellar and supraspinatus tendons of both mice and rats. These tendons are functionally distinct and are also among the most commonly injured, and therefore of important translational interest. Approximately one-third of the filtered transcriptome was differentially regulated between Achilles, forepaw flexor, patellar and supraspinatus tendons within either mice or rats. Nearly two-thirds of the transcripts that are expressed in anatomically similar tendons were different between mice and rats. The overall findings from this study identified that although tendons across the body share a common anatomical definition based on their physical location between skeletal muscle and bone, tendon is a surprisingly genetically heterogeneous tissue. ABSTRACT: Tendon is a functionally important connective tissue that transmits force between skeletal muscle and bone. Previous studies have evaluated the architectural designs and mechanical properties of different tendons throughout the body. However, less is known about the underlying transcriptional differences between tendons that may dictate their designs and properties. Therefore, our objective was to develop a comprehensive atlas of the transcriptome of limb tendons in adult mice and rats using systems biology techniques. We selected the Achilles, forepaw digit flexor, patellar, and supraspinatus tendons due to their divergent functions and high rates of injury and tendinopathies in patients. Using RNA sequencing data, we generated the Comparative Tendon Transcriptional Database (CTTDb) that identified substantial diversity in the transcriptomes of tendons both within and across species. Approximately 30% of filtered transcripts were differentially regulated between tendons of a given species, and nearly 60% of the filtered transcripts present in anatomically similar tendons were different between species. Many of the genes that differed between tendons and across species are important in tissue specification and limb morphogenesis, tendon cell biology and tenogenesis, growth factor signalling, and production and maintenance of the extracellular matrix. This study indicates that tendon is a surprisingly heterogenous tissue with substantial genetic variation based on anatomical location and species.

Non-treatment of stable ramp lesions does not degrade clinical outcomes in the setting of primary ACL reconstruction.

PURPOSE: The purpose of this study was to evaluate the clinical outcomes of various methods of treatment of stable and unstable ramp lesions compared to patients with no meniscal pathology at the time of primary ACL reconstruction. METHODS: All patients with a preoperative MRI performed at our facility who were enrolled in an institutional ACL registry and 1-year clinical follow-up were identified. A musculoskeletal radiologist reviewed preoperative MRI scans for evidence of a ramp lesion. Ramp lesions were classified as stable if a peripheral tear of the posterior horn of the medial meniscus was identified by MRI, but did not displace into the medial compartment with anteriorly directed probing at the time of surgery. Ramp lesions were classified as unstable if a tear was identified by preoperative MRI at the meniscocapsular junction and the meniscus was displaceable into the medial compartment with probing. Reoperation rates for ACL graft failure or recurrent medial meniscus pathology were collected. Patient-reported outcome scores (IKDC, SF12 PCS, SF12 MCS, and Marx Activity scale) were recorded at baseline and final follow-up. RESULTS: A total of 162 patients were included in the analysis with median 2-year (range 1-5 years) clinical follow-up. Patients with a repaired unstable ramp lesion had a significantly higher likelihood of reoperation for recurrent medial meniscus pathology than patients without meniscal pathology at the time of index surgery. Patients with an untreated stable ramp lesion had a similar rate of reoperation when compared to patients without meniscal pathology. At final follow-up, there was no difference between groups in IKDC score, SF12 PCS/MCS, or Marx activity score or change in any score. CONCLUSIONS: Patients with untreated stable ramp lesions have similar clinical outcomes at median 2-year (range 1-5 years) follow-up when compared to patients without a ramp lesion. Treatment of stable ramp lesions at the time of ACL reconstruction does not have clinical benefit. LEVEL OF EVIDENCE: III.

The role of biologic agents in the management of common shoulder pathologies: current state and future directions.

The field of orthopedic surgery has seen a rapid increase in the use of various biologic agents for the treatment of common musculoskeletal injuries. Most biologic agents attempt to harness or mimic naturally occurring growth factors, cytokines, and anti-inflammatory mediators to improve tissue healing and recovery. The most commonly used biologic agents are platelet-rich plasma and cells derived from bone marrow aspirate and adipose tissue. These agents have become increasingly popular despite a relative dearth of clinical data to support their use. Much confusion exists among patients and physicians in determining the role of these agents in treating common shoulder pathologies, such as glenohumeral osteoarthritis, rotator cuff tears, and tendinopathy. This article reviews the basic science and clinical evidence for the most commonly used biologic agents in the management of common shoulder pathology.

Cardiovascular screening of Olympic athletes reported by chief medical officers of the Rio 2016 Olympic Games.

OBJECTIVE: The IOC recommends periodic cardiovascular screening of athletes, but the adoption of these recommendations is unknown. The purpose of this investigation was to evaluate and compare cardiovascular screening practices of countries participating in the Rio 2016 Olympic Games. METHODS: A list of chief medical officers (CMOs) was compiled by the IOC during the 2016 Olympic Games. CMOs were requested to complete an online survey about cardiovascular screening of their countries' Olympic athletes. Comparisons of screening practices were made by categorising countries by continent, gross domestic product (GDP) per capita and size of athlete delegation. RESULTS: CMOs for 117/207 (56.5%) countries participating in the 2016 Olympic Games were identified. 94/117 countries (80.3%) completed the survey, representing 45.4% of all countries and 8805/11 358 (77.5%) of all 2016 Olympic athletes. Most of the countries surveyed (70.2%) perform annual cardiovascular screening. Among the survey respondents, all or most athletes from each country were screened at least once with the following components: personal history (86.2% of countries), family history (85.1%), physical examination (87.2%), resting ECG (74.5%), echocardiogram (31.9%) and stress test (30.8%). Athletes were more likely to be screened with ECG in countries with relatively larger athlete delegation (OR 2.05, 95% CI 1.10 to 3.80, p=0.023) and with higher GDP per capita (OR 1.69, 95% CI 1.11 to 2.57, p=0.014). CONCLUSION: Most of the responding countries perform annual cardiovascular screening of Olympic athletes, but there are differences in the components used. Athletes from countries with larger athlete delegations and higher GDP per capita were more likely to be screened with ECG.

Editorial Commentary: The Quest to Prevent Knee Anterior Cruciate Ligament Bone Tunnel Widening Continues.

The exploration of methods to improve healing of a tendon graft in a bone tunnel in anterior cruciate ligament reconstruction has been a subject of basic and translational research for over 30 years. It is well recognized that the graft attachment site to the bone represents the "weak link" in the early healing period. We as clinicians search for methods to augment healing of the tendon graft in the bone tunnel. Agents and techniques that improve osteoinduction may improve healing. Implanted chondrocytes may promote tendon-to-bone healing by participating in new bone formation or, alternatively, by providing signaling molecules that stimulate local or distant endogenous cells. Tracking of cell fate after implantation will be required to further delineate biologic mechanisms.