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The expression of some chemokines and chemokine receptors is induced during the development of post-traumatic osteoarthritis (PTOA), but their involvement in the pathogenesis of the disease is unclear. The goal of this study was to test whether CCL21 and CXCL13 play a role in PTOA development. For this purpose, we evaluated the expression profiles of the chemokines Ccl21 and Cxcl13, matrix metalloproteinase enzymes Mmp3 and Mmp13, and inflammatory cell markers in response to partial medial meniscectomy and destabilization (MMD). We then assessed the effect of local administration of CCL21 neutralizing antibody on PTOA development and post-knee injury inflammation. The mRNA expression of both Ccl21 and Cxcl13 was induced early post-surgery, but only Ccl21 mRNA levels remained elevated 4 weeks post-surgery in rat MMD-operated knees compared to controls. This suggests that while both CXCL13 and CCL21 are involved in post-surgery inflammation, CCL21 is necessary for development of PTOA. A significant increase in the mRNA levels of Cd4, Cd8 and Cd20 was observed during the first 3 days post-surgery. Significantly, treatment with CCL21 antibody reduced post-surgical inflammation that was accompanied by a reduction in the expression of Mmp3 and Mmp13 and post-MMD cartilage degradation. Our findings are consistent with a role for CCL21 in mediating changes in early inflammation and subsequent cartilage degeneration in response to knee injury. Our results suggest that targeting CCL21 signaling pathways may yield new therapeutic approaches effective in delaying or preventing PTOA development following injury., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The aim of this study was to propose and validate a new six-item topographical classification of knee bone marrow lesions in coronal MRI images, to provide an easy-to-use aid to describe their location in a more reproducible and accurate way., Methods: This study was conducted in four phases. The first was to do a literature search for methods of describing bone marrow lesions in MRI of the knee. The second was creation of a six-area topographic classification of bone marrow lesions in coronal MRI of the knee. The third phase was selection of cases with bone marrow lesions on knee MRI performed in a single hospital between January of 2017 and December of 2018. The fourth phase was categorization of the bone marrow lesions' location according to the new proposed classification by three independent examiners, two orthopedic surgeons and one radiologist. Patient's demographic data and associated lesions were collected. The inter-observer and intra-observer reliability of the proposed classification was then calculated., Results: MRI examination of 4000 patients were studied and in 520 patients a total of 666 bone marrow lesions were identified and their location classified using the new system. The inter-observer and intra-observer reliability analysis found a Fleiss' Kappa value of 0.96 (0.95-0.97) and 0.97 (0.96-0.97), respectively, confirming the high reproducibility of the proposed classification., Conclusions: The proposed six-location classification of bone marrow lesions is highly reproducible and can help researchers develop studies and share information in a more accurate and reliable way. The correct classification of bone marrow lesions can lead to a more accurate description of this pathology and help clinicians to propose appropriate therapies for this group of patients., Level of Evidence: V.

Introduction: Injuries to the quadriceps extensor mechanism are rare in patients with Osteogenesis Imperfecta (OI). To the best of our knowledge, non-union of the patella in OI, either as an isolated problem or in combination with an acute fracture, has not been previously reported., Case Report: We describe how we surgically approached both the fracture and the non-union simultaneously. The surgical technique and steps are described in detail. Post-operative course was uneventful and the outcome was favorable, with full return of function for the patient., Conclusion: A review of various knee extensor mechanism injuries in OI is described as illustrated in a single patient. The unusual simultaneous surgical treatment of a non-union and an acute fracture in the same patella shows that despite the severely compromised bone in this rare bone disease the bone still has a capacity to heal with a functional outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kloen, Hamdy and Bech.)

Very few case reports have been reported on traumatic separation of the bipartite patella along with quadriceps tendon rupture. These reports relate to separation of superolateral bipartite patella (Saupe type 3). We describe a new variant which to our knowledge has not been described or classified so far, which is purely a superior bipartite patella with traumatic separation and complete functional disruption of the extensor mechanism of the knee in a young patient working in the army which was managed with open reduction and internal fixation along with repair of the extensor mechanism of the knee achieving complete functional recovery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A description of the precise locations of ligamentous and myotendinous injury patterns of acute posterolateral corner (PLC) injuries and their associated osseous and neurovascular injuries is lacking in the literature., Purpose: To characterize the ligamentous and myotendinous injury patterns and zones of injury that occur in acute PLC injuries and determine associated rates of peroneal nerve palsies and vascular injuries, as well as fracture and dislocation., Study Design: Case series; Level of evidence, 4., Methods: We retrospectively identified all patients treated for an acute multiligament knee injury (MLKI) at our level 1 trauma center from 2001 to 2018. From this cohort, all patients with PLC injuries were identified. Demographics, involved ligaments and tendons, neurovascular injury, and presence of fracture and dislocation were compared with the larger multiligament knee cohort. Incidence and location of injury of PLC structures-from proximal to midsubstance and distal injury-were recorded., Results: A total of 100 knees in 100 patients were identified as having MLKIs. A total of 74 patients (74%) had lateral-sided ligament injuries. Of these, 23 (31%) had a peroneal nerve palsy associated with their injury; 10 (14%), a vascular injury; and 23 (31%), a fracture. Patients with PLC injuries had higher rates of peroneal nerve injury as compared with those having acute MLKIs without a PLC injury (31% vs 4%; P = .005). Patients with a complete peroneal nerve palsy (n = 17) were less likely to regain function than those with a partial peroneal nerve palsy (n = 6; 12% vs 100%; P < .0001). Complete injury to the lateral collateral ligament (LCL) occurred in 71 of 74 (96%) PLC injuries, with 3 distinct patterns of injury demonstrated. Fibular avulsion of the LCL was the most common zone of injury (65%), followed by femoral avulsion (20%) and midsubstance tear (15%). Location of injury to the LCL was associated with the rate of peroneal nerve injury, with midsubstance tears and fibular avulsions associated with higher rates of peroneal nerve injury., Conclusion: MLKIs with involvement of the PLC are more likely to suffer peroneal nerve injury. The LCL is nearly always involved, and its location of injury is predictive of peroneal nerve injury. Patients with a complete peroneal nerve palsy at presentation are much less likely to regain function.

Cartilage injuries in the knee are common and can occur in isolation or in combination with limb malalignment, meniscus, ligament, and bone deficiencies. Each of these problems must be addressed to achieve a successful outcome for any cartilage restoration procedure. If nonsurgical management fails, surgical treatment is largely based on the size and location of the cartilage defect. Preservation of the patient's native cartilage is preferred if an osteochondral fragment can be salvaged. Chondroplasty and osteochondral autograft transfer are typically used to treat small (<2 cm) cartilage defects. Microfracture has not been shown to be superior to chondroplasty alone and has potential adverse effects, including cyst and intralesional osteophyte formation. Osteochondral allograft transfer and matrix-induced autologous chondrocyte implantation are often used for larger cartilage defects. Particulated juvenile allograft cartilage is another treatment option for cartilage lesions that has good to excellent short-term results but long-term outcomes are lacking.

Osteoarthritis (OA) leads to joint pain from intraarticular inflammation with articular cartilage erosion, deterioration of joint function and abnormal subchondral bone structure. Besides aging, chronic repetitive joint injury is a common risk factor in young individuals. Nevertheless, whether OA is associated with bone loss at other skeletal sites is unclear. Since OA-associated proinflammatory cytokines-some of which are osteoclastogenic factors-are often detected in the circulation, we hypothesized that the injury-induced knee OA could result in widespread osteopenia at bone sites distant to the injured knee. Here we performed anterior cruciate ligament transection (ACLT) to induce knee OA in one limb of female Sprague-Dawley rats and determined bone changes post-OA induction by micro-computed tomography and computer-assisted bone histomorphometry. We found that although OA modestly altered bone density, histomorphometric analyses revealed increases in bone resorption and osteoid production with impaired mineralization. The bone formation rate was also reduced in OA rats. In conclusions, ACLT in young growing rats induced microstructural defects in the trabecular portion of weight-bearing (tibia) and non-weight-bearing bones (L5 vertebra), in part by enhancing bone resorption and suppressing bone formation. This finding supports the increasing concern regarding the repetitive sport-related ACL injuries and the consequent bone loss.

Aim: A limited healing response to focal cartilage lesions is frequently encountered in the clinical cartilage pathology. This study compares the gene expression patterns of damaged and undamaged regions of cartilage obtained from the same patient with focal cartilage lesions. The aim of this study is to provide new genes and proteins, which may be a potential future target of research., Methods: During the autologous chondrocyte implantation (MACI) surgery, cartilage tissues (healthy non-weight bearing and Damaged-lesion side) were obtained from 10 patients with knee focal cartilage lesions. The degeneration status of the cartilage was characterized according to ICRS criteria. Whole genome microarray gene expression profiling was performed and some of the differentially regulated genes were validated with RT-PCR., Results: Damaged and undamaged non-weight bearing cartilage showed distinct gene expression profiles. Genes involved in cell signaling, matrix degradation, hypoxia, and the inflammatory response showed significant up- or down-regulation. In the focal lesions, expression of genes such as HIF1α, TIMP-2, EID1, EID2, NCOA3, NBR1, SP100, and HSP90AA1 was significantly higher compared to healthy non-weight bearing cartilage from the same joint, whereas TIMP-4 was lower., Conclusion: The genes examined in this study differ distinctly between focal cartilage (ICRS 3-4) lesions and undamaged sites of the same joint. We believe that the data set forth in this study may be used for clinical purposes and be a guide in the development of new biological approaches for therapy.

Introduction: rheumatoid arthritis (RA) is a common autoimmune disease with unknown etiology and pathogenesis. Biomarkers have the potential to aid in the clinical diagnosis of the disease, or to provide means of detecting early signs of the disease. Evaluating Melanoma associated antigen genes (MAGE-1) mRNA expression rate in synovial fluid cells and serum levels of anti-cyclic citrullinated peptides (anti-CCP) and rheumatoid factor (RF) for RA early diagnosis., Methods: a total of 213 subjects were enrolled in the study, 135 RA patients and 78 normal subjects with traumatic knee joints (control group). Serum RF and anti-CCP were estimated quantitatively using ELISA. MAGE-1 mRNA expression rate was analyzed by RT-PCR., Results: a significant increase in serum levels of RF IgM and anti-CCP in RA patients compared to the controls. A positively significant correlation was found between serum anti-CCP and RF IgM. The expression rate of MAGE-1 mRNA was 100% in RA patients versus the controls (0%). The specificity and the sensitivity of the three biomarkers was 100%., Conclusion: the high expression rate of MAGE-1 in synovial fluid cells of RA patients is encouraging its utilization as a diagnostic biomarker for RA. The combined use of MAGE-1 transcript in synovial fluid cells, serum RF and anti-CCP is recommended for improving early diagnostic ability of RA., Competing Interests: The authors declare no competing interests., (Copyright: Al-Qtaitat Aiman et al.)

Purpose: The aim of the present study was to translate, cross-culturally adapt, and assess the psychometric properties of the Pedi-IKDC and Pedi-FABS scores in the Italian paediatric population with various knee pathologies., Methods: In accordance with the Paediatric Anterior Cruciate Ligament Monitoring Initiative (PAMI) research protocol, the original English versions of the questionnaires were translated into Italian. All patients aged 8-16 and scheduled for knee surgery were considered eligible in the study. An open-source platform was implemented to collect responses to the surveys which included general patient information, the questionnaires Pedi-IKDC, and Pedi-FABS. Two surveys were sent under stable clinical conditions before surgery (Q 1 and Q 2 ); a third survey was sent 3-4 months after surgery (Q 3 ). The following properties were calculated: reliability, internal consistency, criterion validity, responsiveness, and floor/ceiling effects., Results: Eighty-nine patients completed Q 1 , 81 patients completed Q 2 , and 49 patients completed Q 3 . Both questionnaires demonstrated acceptable properties. Pedi-IKDC: standard error of measurement (SEM) = 4.4, smallest detectable change (SDC) = 12.3, interclass correlation coefficient (ICC) = 0.96, Cronbach alpha (α) = 0.92, moderate-to-low correlation to Pedi-FABS, effect size (ES) = 0.79, standardized response mean (SRM) = 0.86, floor = 0%, ceiling = 22%. Pedi-FABS: SEM = 2.1, SDC = 5.8, ICC = 0.94, Cronback alpha (α) = 0.93, moderate-to-low correlation to Pedi-IKDK, ES = 0.60, SRM = 0.51, floor = 19%, ceiling = 0%., Conclusions: The Italian version of Pedi-IKDC and Pedi-FABS is valuable tools for patient assessment, by demonstrating good psychometric properties. In clinical setting, these questionnaires can be used to properly evaluate outcomes in Italian pediatric patients with knee pathologies., Level of Evidence: II.

Purpose: To determine the incidence and characterize the severity of iatrogenic cartilage injuries., Methods: Technique videos of arthroscopic femoral acetabular impingement procedures and meniscus repairs on VuMedi (n = 85) and Arthroscopy Techniques (n = 45) were reviewed and iatrogenic cartilage injuries were identified and graded (minor, intermediate, and major injury) by 2 independent reviewers. To demonstrate that even minor injuries on a cellular scale result in damage, a bovine osteochondral explant was used to create comparable minor iatrogenic injuries at varied forces that do not disrupt the articular surface (1.5 N, 2.5 N, and 9.8 N). Dead chondrocytes at the site of injury were stained with ethidium homodimer-2 and imaged with an Olympus FV1000 confocal microscope. χ 2 tests were used for analysis; all results with P < .05 were considered significant., Results: In total, 130 videos of arthroscopic meniscus and femoral acetabular impingement procedures were analyzed and the incidence of iatrogenic cartilage injury was 73.8%. There were 110 (70.0%) minor, 35 (22.3%) intermediate, and 11 (7.0%) major iatrogenic injuries. All forces tested in the minor injury bovine model resulted in chondrocyte death at the site of contact., Conclusions: Iatrogenic articular cartilage injuries are common in arthroscopy, occurring in more than 70% of the surgeon-published instructional videos analyzed. At least some chondrocyte death occurs with minor simulated iatrogenic injuries (1.5 N)., Clinical Relevance: The high rate of cartilage damage during arthroscopic technique videos likely under-represents the true incidence in clinical practice. Cell death occurs in the bovine minor injury model with minimal contact forces. This suggests iatrogenic cartilage damage during arthroscopy could contribute to clinical outcomes., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background Tumor-like cortical irregularities at the posterior distal femur are common incidental findings in adolescents, but the origin of these irregularities is debated. Purpose To compare the prevalence of distal femoral cortical irregularities (DFCIs) at different tendon attachment sites in youth competitive alpine skiers with that in young adults. Materials and Methods In this secondary analysis of a prospective trial, unenhanced 3-T knee MRI scans obtained in youth competitive alpine skiers were compared with images in control participants of the same age from 2014 to 2019 (Cantonal Ethics Committee Zurich registry number: KEK-ZH-2017-01395) for presence of DFCIs at the femoral attachment of the medial head of the gastrocnemius muscle (MHG) and/or lateral head of the gastrocnemius muscle (LHG) and adductor magnus tendon by two radiologists. DFCI size and tendon attachment position were measured. Tendon attachment position and associated MRI findings (meniscus, cartilage, bone marrow edema, joint effusion, ligaments, tendons) were examined for an association with DFCI. Pearson χ 2 , Student t test, logistic regression, and κ statistics were applied. Results Unilateral knee MRI scans obtained in 105 skiers (mean age, 14.8 years ± 0.6 [standard deviation]; 66 boys) and in 105 control participants (mean age, 14.6 years ± 0.5; 59 boys) were evaluated. DFCIs were found in 61 of 105 skiers (58%; 95% confidence interval [CI]: 48.5%, 67.2%) compared with 28 of 105 control participants (27%; 95% CI: 18.9%, 35.7%) ( P < .001). Two skiers had more than one DFCI. Distribution of DFCIs for skiers and control participants was 60 of 63 (95.2%) and 26 of 28 (92.8%) at the MHG, three of 63 (4.8%) and one of 28 (3.6%) at the LHG, and zero of 63 (0%) and one of 28 (3.6%) at the adductor magnus attachment site, respectively. Interreader agreement was almost perfect (κ = 0.87; 95% CI: 0.80, 0.93). The mean size of MHG-related DFCIs in skiers (3.7 mm) was not different compared to the size of those in control participants (3.4 mm) ( P = .32), nor was a difference found for the MHG tendon attachment position in knees with DFCI (63.9 mm vs 63.0 mm, P = .83) or without DFCI (63.6 mm vs 62.8 mm, P = .86). Regarding associated MRI findings, increased signal intensity of the MHG tendon showed a significant association with MHG-related DFCI in both groups ( P = .01 for both). Conclusion A distal femoral cortical irregularity at the attachment sites of tendons was a frequent incidental finding on knee MRI scans, with an increased prevalence in youth competitive alpine skiers. © RSNA, 2020 Online supplemental material is available for this article.

Meniscal root tears are an increasingly recognized injury leading to notable functional limitations, potential rapid cartilage deterioration of the affected compartment, and subsequent risk of total knee arthroplasty if left untreated. Repair of these tears is advised when articular cartilage remains intact because both medial and lateral meniscus root repairs have demonstrated favorable results. Recent literature demonstrates decreased rates of osteoarthritis and arthroplasty after medial meniscus root repair compared with partial meniscectomy and nonsurgical management. The transtibial pull-out repair technique is most commonly used and provides a biomechanically strong suture construct with standard and familiar knee arthroscopy portals. Furthermore, repair has recently been shown to be economically effective by decreasing overall societal healthcare costs when compared with more conservative management strategies. This review outlines the evaluation, treatment, and documented outcomes of meniscal root repair, which is imperative to the preservation of knee function and maintaining quality of life.

Aim: To evaluate the safety, pain, functional and structural improvements after autologous adipose-derived mesenchymal stem cell (ADMSC) therapy in combination with arthroscopic abrasion arthroplasty in focal chondral defects of the knee. Methods: Eight patients with a focal full thickness chondral defect of the knee underwent arthroscopic abrasion arthroplasty followed by postoperative intra-articular injections of autologous ADMSCs (50 × 10 6 ADMSCs at baseline and 6 months). Clinical outcome was assessed using numeric pain rating scale, Knee Injury and Osteoarthritis Outcome Score and the Western Ontario and McMaster Universities Osteoarthritis Index. Structural outcome was determined by magnetic resonance imaging. Outcome was assessed over 24 months. Results: No serious adverse events occurred. Participants observed clinically significant improvement in pain and function. Magnetic resonance imaging analysis showed cartilage regeneration with T2 mapping values comparable to hyaline cartilage. Conclusion: Arthroscopic abrasion arthroplasty in combination with intra-articular ADMSC therapy results in reproducible pain, functional and structural improvements with regeneration of hyaline-like cartilage. Trial registration number: ACTRN12617000638336.

Background: The development of heterotopic ossification (HO) might nullify any benefit of multiple-ligament reconstruction of the knee joint. The purpose of this study was to investigate the incidence and the specific explanatory factors for the development of HO after multiple-ligament reconstruction of the knee joint., Methods: From January 2011 to June 2016, 72 consecutive patients with knee dislocations received multiple-ligament reconstructions, of which 57 (79%) were available for a minimum follow up of 12 months and were included in this study. Anteroposterior (AP) and lateral radiographs were reviewed for all patients. This knee dislocation cohort was separated into two groups based on the presence or absence of HO for comparisons. In addition, the HO group was divided into three subgroups based on a modified quadrant grading system introduced by the senior author for further evaluation. Multivariate logistic regression analysis was then performed to identify specific explanatory factors predicting development of HO in patients after multiple-ligament reconstructions of the knee joint., Results: Among the 72 consecutive patients, 57 (79%) were available for the clinical evaluations with an average period of 28.4 months (range, 12-51 months). Twenty-one patients (37%) showed radiological evidence of HO. The HO group (n = 21) showed significantly inferior results of knee flexion angle compared with the non-HO group (n = 36) (HO group vs. non-HO group: 124 ± 13° vs. 132 ± 5°; P<0.01). According to the quadrant grading system, there were seven patients with grade I, nine with grade II, and five with grade III HO. Subgroup analysis further revealed that higher HO grade would lead to lower knee flexion angle. In addition, multivariate regression analysis showed that concomitant posterior cruciate ligament reconstruction was the only independent explanatory factor predicting the development of HO after multiple-ligament reconstruction of the knee joint (P=0.018; odds ratio, 8.75; 95% confidence interval, 1.69-39.7)., Conclusion: In this cohort of knee dislocations, the incidence of HO development following multiple-ligament reconstruction was 37%, with grade III HO showing the most inferior range of motion outcome. Moreover, concomitant posterior cruciate ligament reconstruction was the only independent predictor for the development of HO., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Multipotent Mesenchymal Stem/Stromal Cells (MSCs) are widely used in cellular therapy for joint repair. However, the use of MSC therapies is complicated by a lack of understanding of the behaviour of cells and repair within the joint. Current methods of MSC tracking include labelling the cells with Super Paramagnetic Iron Oxide nanoparticles (SPIOs). However, standard acquisition sequences (T 2 and T 2 *) give poor anatomical definition in the presence of SPIOs. To avoid anatomical compromise in the presence of SPIOs, we have investigated the use of Ultra-short Echo Time (UTE) MRI, using a 3D cones acquisition trajectory. This method was used to track SPIO labelled MSC injected into joints containing osteochondral defects in experimental sheep. This study demonstrates that multiple echo times from UTE with 3 T MRI can provide excellent anatomical detail of osteochondral defects and demonstrate similar features to histology. This work also monitors the location of SPIO-labelled cells for regenerative medicine of the knee with MRI, histology, and Prussian blue staining. With these methods, we show that the SPIOs do not hone to the site of defect but instead aggregate in the location of injection, which suggests that any repair mechanism with this disease model must trigger a secondary process.

Purpose/Aim: Knee meniscus is a wedge-shaped fibrocartilaginous tissue, playing important roles in maintaining joint stability and function. Injuries to the meniscus, particularly with the avascular inner third zone, hardly heal and frequently progress into structural breakdown, followed by the initiation of osteoarthritis. As the importance of meniscus in joint function and diseases is being recognized, the field of meniscus research is growing. Not only development, biology, and metabolism but also injury, repair, and healing of meniscus are being actively investigated. As meniscus functions as an integrated unit of a knee joint, in vivo models with various species have been the predominant method for studying meniscus pathophysiology and for testing healing/regeneration strategies. However, in vivo models for meniscus studies suffer from low reproducibility and high cost. To complement the limitations of in vivo animal models, several types of meniscus explants have been applied as highly controlled, standardized in vitro models to investigate meniscus metabolism, pathophysiology, and repair or regeneration process. This review summarizes and compares the existing meniscus explant models. We also discuss the advantages and disadvantages of each explant model. Conclusion: Despite few outstanding challenges, meniscus explant models have potential to serve as an effective tool for investigations of meniscus metabolism, injury, repair and healing.

Objective: Acute synovial inflammation following joint trauma is associated with posttraumatic arthritis. Synovial macrophages have been implicated in degenerative changes. In this study, we sought to elucidate the role of intra-articular macrophages in the acute inflammatory response to fracture in the mouse knee., Method: A closed articular fracture was induced in two models of synovial macrophage depletion: genetically-modified MaFIA mice administered AP20187 to induce programmed macrophage apoptosis, and wild-type C57BL/6 mice administered clodronate liposomes, both via intra-articular injection. Synovial inflammation, bone morphology, and levels of F4/80+ macrophages, NOS2+ M1 macrophages, and CD206+ M2 macrophages were quantified 7 days after fracture using histology and micro-computed tomography., Results: Intra-articular macrophage depletion with joint injury did not reduce acute synovitis or the number of synovial macrophages 7 days after fracture in either macrophage-depleted MaFIA mice or in clodronate-treated C57BL/6 mice. In macrophage-depleted MaFIA mice, macrophage polarity shifted to a dominance of M1 macrophages and a reduction of M2 macrophages in the synovial stroma, indicating a shift in M1/M2 macrophage ratio in the joint following injury. Interestingly, MaFIA mice depleted 2 days prior to fracture demonstrated increased synovitis (P = 0.003), reduced bone mineral density (P = 0.0004), higher levels of M1 macrophages (P = 0.013), and lower levels of M2 macrophages (not statistically significant, P=0.084) compared to control-treated MaFIA mice., Conclusion: Our findings indicate that macrophages play a critical immunomodulatory role in the acute inflammatory response surrounding joint injury and suggest that inhibition of macrophage function can have prominent effects on joint inflammation and bone homeostasis after joint trauma., (Copyright © 2020 Osteoarthritis Research Society International. All rights reserved.)

A 24-yr-old male soccer player presented with a 7-yr history of left posterior knee "looseness." Evaluation 7 yrs ago, at the time of initial injury, revealed atraumatic anterior and posterior cruciate ligament sprains. On representation, the patient described the pain as a constant, dull ache, 3/10, but his biggest complaint was this feeling of "instability" and looseness where his knee would "buckle" 3-4 times a week. Physical examination was positive for grade 1 posterior drawer and grade 1 posterior sag signs. Reverse KT-1000 testing showed a 3-mm side-to-side difference. Sonographic evaluation confirmed magnetic resonance imaging findings of posterior cruciate ligament laxity and buckling and a small cystic lesion abutting the posteromedial margin of the distal 1/3 of the posterior cruciate ligament. After a trial of physical therapy, the patient elected to undergo experimental injection of dextrose hyperosmolar solution. This resulted in resolution of the cyst and reverse KT-1000 measurements improved to a side-to-side difference of 1 mm. The patient's subjective feeling of looseness and instability resolved by 7 wks.

This article summarises the clinical decision tools available to help decide when acute lower limb joint injuries should be referred for plain film radiography. The Ottawa foot and ankle rules are a tool for deciding whether to refer a patient for X-ray or not. The rules are highly sensitive, gaining National Institute for Health and Care Excellence recommendation in the UK, although they have limited benefit in some patient groups, such as those with peripheral neuropathy. The Ottawa knee rules are highly sensitive but less specific than the Pittsburgh decision rules. Although the Pittsburgh rules are more specific, they have been less extensively investigated and, unlike the Ottawa rules, are not National Institute for Health and Care Excellence recommended. A major barrier to use of these rules in clinical practice is the concern of litigation, although National Institute for Health and Care Excellence recommendation should reassure clinicians and thus reduce the amount of unnecessary radiation exposure.

Background: Bone bruising of the posterolateral tibial plateau and the lateral femoral condyle sulcus terminalis has a well-established association with anterior cruciate ligament (ACL) tears. Impaction fractures of the femur and tibia may occur in these locations; however, there is a paucity of literature describing these fractures., Purpose: The primary objective was to quantify the incidence, size, and location of impaction fractures of the posterolateral tibial plateau and lateral femoral condyle in patients with primary ACL tears. The secondary objective was to investigate the association between impaction fractures and concomitant meniscal and ligamentous injuries., Study Design: Case series; Level of evidence 4., Methods: Patients with available magnetic resonance imaging (MRI) scans who were treated for primary ACL tear by a single surgeon were identified. MRI scans were reviewed with denotation of posterolateral tibial and femoral condylar contusions and displaced impaction fractures. Measurements of the lateral tibial plateau were taken in all patients with displaced lateral tibial plateau fractures and in a subset of control patients without tibial plateau fracture present to characterize the size and location of the bony lesion. Associations of impaction fractures with concomitant meniscal or ligamentous injuries were evaluated through use of chi-square testing., Results: There were 825 knees identified with available MRI scans. Lateral tibial plateau bone bruising was present in 634 knees (76.8%), and lateral femoral condyle bone bruising was present in 407 knees (49.3%). Posterolateral tibial plateau impaction fractures were present in 407 knees (49.3%), and lateral femoral condylar impaction fractures were present in 214 knees (25.9%). Patients with posterolateral tibial plateau impaction fractures were older than patients without these fractures (42.6 vs 32.7 years; P < .001), whereas patients with lateral femoral condylar impaction fractures were younger (23.8 vs 32.7 years; P < .001). There were 71 knees (8.6%) with a posterolateral tibial plateau impaction fracture with greater than 10% loss of lateral tibial plateau depth, and this group had an increased incidence of lateral meniscus posterior root tears (22.1% vs 12.0%; P = .02)., Conclusion: Posterolateral tibial plateau impaction fractures occurred with a high incidence (49.3%) in patients with primary ACL tears and demonstrated an increased association with lateral meniscus posterior horn root tears as their size increased. Lateral femoral condylar impaction fractures occurred in 25.9% of patients with primary ACL tears and entailed an increased incidence of lateral meniscal tears and medial meniscal ramp lesions.

Characteristic injury patterns have been described in pedestrians struck by motor vehicles. The common injury pattern seen in upright pedestrians consists of a triad of head, pelvis, and lower extremity trauma. There are several factors such as vehicular type, design, mass and speed, and impact surfaces that influence the type and distribution of these injuries. We report a case that illustrates the importance of examination of the knee at autopsy when the typical lower extremity diaphyseal fractures that are usually seen in a motor vehicle-pedestrian collision are absent.

Background: To study the role of lysosomal decomposition and elimination of old bone matrix, as well as the mechanism of promoting chondrocyte growth and bone recovery through the perspective of TFEB-mediated lysosomal autophagy., Methods: Rat models of acute knee injury were designed, and autophagy flow was detected by injection of autophagy inhibitors 3-methyladenine. Autophagy flow was detected by RFP-GFP-LC3 double fluorescence molecule. The expression of TFEB, DRAM, MAPLC3, and MITF were analyzed by Western blot, and the expression of genes NITF, Bcl2, and TYR in rat cartilage tissues were detected by RT-PCR., Results: The number of autophagosomes was increasing in the auto group compared with the inhibitor-auto group and normal group. There was a significant difference of LC3 levels in the auto group and inhibitor-auto group compared with the normal control. The expression of TFEB, DRAM, MAPLC3, and MITF proteins by Western blot analysis were significantly increased in the auto group and decreased in the inhibitor-auto group. The expression of NITF, Bcl2, and TYR by RT-PCR determination were higher in the auto group and inhibitor-auto group than the normal group., Conclusions: Autophagy can inhibit apoptosis, promote chondrocyte growth and bone regeneration, and restore knee joint injury of rats. The main mechanism is to promote the effect of TFEB-mediated lysosomal autophagy.

The relative velocity of the tibiofemoral surfaces during gait before and after partial-ACL and full MCL transection (p-ACL/MCL Tx) was examined in an ovine model (N = 5) and the relation between the variation in the relative sliding velocity component and gross morphological damage was investigated. We defined the in vivo kinematics of the tibiofemoral joints by using an instrumented spatial linkage and then determining the relative velocity components on the reconstructed femoral condyle surfaces. One major finding was that the magnitude of the relative velocity components was relatively high during the initial stance period of the gait and oscillated with a decaying envelope. Interestingly, for most subjects, the highest value of relative sliding velocity occurred during the stance phase, and not swing. The magnitude of the relative velocity components was increased in 3/5 subjects during stance after an injury. For the lateral compartment, there was a significant correlation (p value = 0.005) between the joint gross morphological damage and the increase in the maximum relative sliding velocity during stance. For the medial compartment, there was a trend (p value < 0.1) between the joint gross morphological score and the increase in the maximum relative sliding velocity during stance, 20 weeks after injury. In conclusion, a connection between an increase in the relative surface velocity and gross morphological damage might be due to an increase in the normal stress and the plowing friction between the surfaces.

This study sought to develop a noninvasive, reliable, clinically relevant, and easy-to-implement mouse model that can be used for investigation of the pathophysiology of PTOA and for preclinical testing of new therapies of PTOA. Accordingly, we have established a closed intraarticular tibial plateau compression loading-induced injury model of PTOA in C57BL/6J mice. In this model, a single application of a defined loading force was applied with an indenter to the tibial plateau of the right knee to create injuries to the synovium, menisci, ligaments, and articular cartilage. The limiting loading force was set at 55 N with the loading speed of 60 N/s. This loading regimen limits the distance that the indenter would travel into the joint, but still yields substantial compression loading energy to cause significant injuries to the synovium, meniscus, and articular cartilage. The joint injury induced by this loading protocol consistently yielded evidence for key histological hallmarks of PTOA at 5-11 weeks post-injury, including loss of articular cartilage, disorganization of chondrocytes, meniscal hyperplasia and mineralization, osteophyte formation, and degenerative remodeling of subchondral bone. These arthritic changes were highly reproducible and of a progressive nature. Because 50% of patients with meniscal and/or ligament injuries without intraarticular fractures developed PTOA over time, this intraarticular tibial plateau compression loading-induced injury model is clinically relevant. In summary, we have developed a noninvasive intraarticular tibial plateau compression loading-induced injury model in the mouse that can be used to investigate the pathophysiology of PTOA and for preclinical testing for new therapies.

Purpose : Aging is a known risk factor for osteoarthritis (OA). Several transgenic rodent models have been used to investigate the effects of accelerated or delayed aging in articular joints. However, age-effects on the progression of post-traumatic OA are less frequently evaluated. The objective of this study is to evaluate how animal age affects the severity of intra-articular inflammation and joint damage in the rat medial collateral ligament plus medial meniscus transection (MCLT+MMT) model of knee OA. Methods : Forty-eight, male Lewis rats were aged to 3, 6, or 9 months old. At each age, eight rats received either an MCLT+MMT surgery or a skin-incision. At 2 months post-surgery, intra-articular evidence of CTXII, IL1β, IL6, TNFα, and IFNγ was evaluated using a multiplex magnetic capture technique, and histological evidence of OA was assessed via a quantitative histological scoring technique. Results : Elevated levels of CTXII and IL6 were found in MCLT+MMT knees relative to skin-incision and contralateral controls; however, animal age did not affect the severity of joint inflammation. Conversely, histological investigation of cartilage damage showed larger cartilage lesion areas, greater width of affected cartilage, and more evidence of hypertrophic cartilage damage in MCLT+MMT knees with age. Conclusions : These data indicate the severity of cartilage damage subsequent to MCLT+MMT surgery is related to the rat's age at the time of injury. However, despite greater levels of cartilage damage, the level of intra-articular inflammation was not necessarily affected in 3, 6, and 9 month old male rats.

Objectives: To evaluate the diagnostic accuracy of dual-energy computed tomography (CT) virtual non-calcium (VNCa) reconstructions for the depiction of traumatic knee bone marrow edema., Methods: Fifty-seven patients (mean age, 50 years; range, 20-82 years) with acute knee trauma further divided into 30 women and 27 men, who had undergone third-generation dual-source dual-energy CT and 3-T magnetic resonance imaging (MRI) within 7 days between January 2017 and May 2018, were retrospectively analyzed. Six radiologists, blinded to clinical and MRI information, independently analyzed conventional grayscale dual-energy CT series for fractures; after 8 weeks, readers evaluated color-coded VNCa reconstructions for the presence of bone marrow edema in six femoral and six tibial regions. Quantitative analysis of CT numbers on VNCa reconstructions was performed by a seventh radiologist. Two additional radiologists, blinded to clinical and CT information, analyzed MRI series in consensus to define the reference standard. Sensitivity, specificity, and the area under the curve (AUC) were the primary metrics of diagnostic accuracy., Results: MRI revealed 197 areas with bone marrow edema (91/342 femoral, 106/342 tibial). In the qualitative analysis, VNCa showed high overall sensitivity (1108/1182 [94%]) and specificity (2789/2922 [95%]) for depicting bone marrow edema. The AUC was 0.96 (femur) and 0.97 (tibia). A cutoff value of - 51 Hounsfield units (HU) provided high sensitivity (102/106 [96%]) and specificity (229/236 [97%]) for differentiating tibial bone marrow edema., Conclusions: In both quantitative and qualitative analyses, dual-energy CT VNCa reconstructions yielded excellent diagnostic accuracy for depicting traumatic knee bone marrow edema compared with MRI., Key Points: • Dual-energy CT (DECT) virtual non-calcium (VNCa) reconstructions are highly accurate in depicting bone marrow edema of the femur and tibia. • Diagnostic confidence, image noise, and image quality were rated as equivalent in VNCa reconstructions and MRI (magnetic resonance imaging) series. • VNCa images may serve as an alternative imaging approach to MRI.

The case of an individual with a bilateral anterior cruciate ligament (ACL) tear combined with a medial meniscus (MM) posterior root tear is described. A 34-year-old Japanese man with bilateral ACL rupture that occurred > 10 years earlier was diagnosed with bilateral ACL tear combined with MM posterior root tear (MMPRT). We performed a transtibial pullout repair of the MMPRT with ACL reconstruction. The tibial tunnels for the MM posterior root repair and ACL reconstruction were created separately. Postoperatively, a good clinical outcome and meniscal healing were obtained. Our surgical technique may thus contribute to anatomical MM posterior root repair and ACL reconstruction., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background Use of a T2 mapping sequence in addition to the conventional knee MRI protocol increases sensitivity to early cartilage lesions but is time consuming. Purpose To test the in vitro validity of quantitative data from an accelerated parallel T2 mapping sequence (combined generalized autocalibrating partially parallel acquisition and model-based accelerated relaxometry by iterative nonlinear inversion [GRAPPATINI]) of the knee and to compare in vivo synthetic images generated with this sequence with those generated with conventional morphologic sequences. Materials and Methods T2 estimations with GRAPPATINI were validated in vitro in comparison with T2 estimations with routine multisection multiecho and reference standard single-section single-echo spin-echo T2 mapping sequences by using a Bland-Altman plot. Synthetic morphologic images (intermediate-weighted sequence, 34-msec echo time; T2-weighted sequence, 80-msec echo time) were compared in vivo with corresponding conventional morphologic turbo spin-echo 3-T sequences by three readers in consecutive patients recruited retrospectively from February to May 2018. Synthetic and conventional morphologic images were compared by using rates of interreader agreement, κ statistics, and rates of findings. Results T2 values with GRAPPATINI were accurate compared with those obtained with the reference single-section single-echo sequence, with slight T2 overestimation (2.7 msec). Sixty-one patients (mean age, 43 years ± 16 [standard deviation]; 32 men) were included. The rate of agreement when one reader used synthetic morphologic images and the other used conventional sequences was not inferior to the rate of agreement when all readers used conventional sequences (upper bounds of 95% confidence intervals of differences between rates of agreement ≤ 4.8%). Interreader agreement was similar for the conventional set alone, the synthetic set alone, and when readers used different sets (two-by-two differences between κ values for all items ≤ 0.15). The rates of findings were not different between synthetic and conventional image sets (all P ≥ .07) except for two items (femoral trochlear cartilage [3.0% vs 0.3%, P = .006] and joint effusion [0.3% vs 2.7%, P = .005]). Conclusion This T2 mapping sequence yields, in one acquisition, accurate T2 values and synthetic morphologic images that are comparable with those obtained with conventional turbo spin-echo sequences. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Fritz in this issue.

Background: Although the femoral tunnel position is crucial to anatomic single-bundle anterior cruciate ligament (ACL) reconstruction, the recommendations for the ideal femoral footprint position are mostly based on cadaveric studies with small sample sizes, elderly patients with unknown ACL status, and 2-dimensional techniques. Furthermore, a potential difference in the femoral ACL footprint position and ACL orientation between ACL-ruptured and ACL-intact knees has not been reported in the literature., Hypothesis: The femoral ACL footprint position and ACL orientation vary significantly between ACL-ruptured and matched control ACL-intact knees., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Magnetic resonance images of the knees of 90 patients with an ACL rupture and 90 matched control participants who had a noncontact knee injury without an ACL rupture were used to create 3-dimensional models of the femur and tibia. The ACL footprints were outlined on each model, and their positions (normalized to the lateral condyle width) as well as ACL orientations were measured with an anatomic coordinate system., Results: The femoral ACL footprint in patients with an ACL rupture was located at 36.6% posterior and 11.2% distal to the flexion-extension axis (FEA). The ACL orientation was 46.9° in the sagittal plane, 70.3° in the coronal plane, and 20.8° in the transverse plane. The ACL-ruptured group demonstrated a femoral ACL footprint position that was 11.0% more posterior and 7.7% more proximal than that of the control group (all P < .01). The same patients also exhibited 5.7° lower sagittal elevation, 3.1° higher coronal plane elevation, and 7.9° lower transverse plane deviation (all P < .01). The optimal cutoff value of the femoral ACL footprint position to prevent an ACL rupture was at 30% posterior and 12% distal to the FEA., Conclusion: The ACL femoral footprint position might be a predisposing factor to an ACL rupture. Patients with a >30% posterior and <12% distal position of the femoral ACL footprint from the FEA might have a 51.2-times increased risk of an ACL rupture.

Seven different autologous chondrocyte implantation (ACI) grafts were used consecutively over a period of 18 years for the treatment of cartilage lesions in the knees. The aim was to evaluate this entire ACI patient series for graft-related or unrelated serious adverse events (SAE), graft failures, and to reveal potential risk factors for these incidents. The study group comprised 151 operated patients: classical periosteum-ACI ( n = 45); ACI-seeded fibrin-collagen patch, fixed by either periosteum ( n = 59), collagen membrane ( n = 15), or fibrin glue ( n = 6); ACI seeded alginate-agarose hydrogel ( n = 14); and biomimetic collagen-hydroxyapatite scaffold injected with the ACI suspension ( n = 12). The covariates analyzed as possible predicting factors were: age, gender, BMI, lesion depth, lesion size, lesion location, previous surgeries, and concomitant procedures. The Kaplan-Meier method for estimating survival curves, and Cox's proportional hazards model to test for covariates, were used in the statistical analysis. The patients in this series, follow-up 10.1 (2.1-18.3) years, encountered 11% of graft-related SAE (risk factors: previous cartilage surgery, age over 40 years, BMI over 25 kg/m 2 , and meniscus surgery) and 10% of graft unrelated SAE (risk factors: meniscus surgery and osteotomy). None of these factors was a risk for definitive graft failure. The 10-year graft survival rate was 86%. Females had 2.8 times higher incidence of graft failures than males. There was a tendency toward higher graft failures after a previous cartilage surgery. Different ACI graft types offered safe and durable cartilage repair. Female gender, age over 40 years, increased weight, previous cartilage surgery, and meniscus loss showed increased risk for revision surgery or graft failures.

Osteochondral lesions (OCs) are typically of traumatic origins but are also caused by degenerative conditions, in primis osteoarthritis (OA). On the other side, OC lesions themselves, getting worse over time, can lead to OA, indicating that chondral and OC defects represent a risk factor for the onset of the pathology. Many animal models have been set up for years for the study of OC regeneration, being successfully employed to test different treatment strategies, from biomaterials and cells to physical and biological adjuvant therapies. These studies rely on a plethora of post-explant investigations ranging from histological and histomorphometric analyses to biomechanical ones. The present review aims to analyze the methods employed for the evaluation of OC treatments in each animal model by screening literature data within the last 10 years. According to the selected research criteria performed in two databases, 60 works were included. Data revealed that lapine (50% of studies) and ovine (23% of studies) models are predominant, and knee joints are the most used anatomical locations for creating OC defects. Analyses are mostly conducted on paraffin-embedded samples in order to perform histological/histomorphometric analyses by applying semiquantitative scoring systems and on fresh samples in order to perform biomechanical investigations by indentation tests on articular cartilage. Instead, a great heterogeneity is pointed out in terms of OC defect dimensions and animal's age. The choice of experimental times is generally adequate for the animal models adopted, although few studies adopt very long experimental times. Improvements in data reporting and in standardization of protocols would be desirable for a better comparison of results and for ethical reasons related to appropriate and successful animal experimentation., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 M. Maglio et al.)

The articular cartilage is an avascular and aneural tissue and its injuries result mostly in osteoarthritic changes and formation of fibrous tissue. Efforts of scientists worldwide are focused on restoration of cartilage with increase in life quality of patients. Novel polymeric polyhydroxybutyrate/chitosan (PCH) porous 3D scaffolds were developed and characterized. The rat mesenchymal stem cells (MSCs) were seeded in vitro on PCH scaffolds by a simple filtration of MSCs suspension over scaffolds using syringe. The chondrogenesis of cell-scaffold constructs was carried out in supplemented chondrogenic cultivation medium. After 2 and 4 weeks of in vitro culturing cell-scaffold constructs in chondrogenic differentiation medium, the cartilage extracellular matrix components like glycosaminoglycans and collagens were identified in scaffolds by biochemical assays and histological and immunohistochemical staining. Preliminary in vivo experiments with acellular scaffolds, which filled the artificially created cartilage defect in sheep knee were done and evaluated. Cells released from the bone marrow cavity have penetrated into acellular PCH scaffold in cartilage defect and induced tissue formation similar to hyaline cartilage. The results demonstrated that PCH scaffolds supported chondrogenic differentiation of MSCs in vitro. Acellular PCH scaffolds were successfully utilized in vivo for reparation of artificially created knee cartilage defects in sheep and supported wound healing and formation of hyaline cartilage-like tissue.

Purpose: To develop a statement on the diagnosis, classification, treatment, and rehabilitation concepts of posterolateral corner (PLC) injuries of the knee using a modified Delphi technique., Methods: A working group of three individuals generated a list of statements relating to the diagnosis, classification, treatment, and rehabilitation of PLC injuries to form the basis of an initial survey for rating by an international group of experts. The PLC expert group (composed of 27 experts throughout the world) was surveyed on three occasions to establish consensus on the inclusion/exclusion of each item. In addition to rating agreement, experts were invited to propose further items for inclusion or to suggest modifications of existing items at each round. Pre-defined criteria were used to refine item lists after each survey. Statements reaching consensus in round three were included within the final consensus document., Results: Twenty-seven experts (100% response rate) completed three rounds of surveys. After three rounds, 29 items achieved consensus with over 75% agreement and less than 5% disagreement. Consensus was reached in 92% of the statements relating to diagnosis of PLC injuries, 100% relating to classification, 70% relating to treatment and in 88% of items relating to rehabilitation statements, with an overall consensus of 81%., Conclusions: This study has established a consensus statement relating to the diagnosis, classification, treatment, and rehabilitation of PLC injuries. Further research is needed to develop updated classification systems, and better understand the role of non-invasive and minimally invasive approaches along with standardized rehabilitation protocols., Level of Evidence: Consensus of expert opinion, Level V.

Introduction: Floating knee is a flail knee joint resulting from fractures of the shafts or adjacent metaphyses of the femur and the ipsilateral tibia. It is usually associated with several complications and mortality. This study was designed to present our experience with the treatment of this injury., Material and Method: This study was performed between January 2004 and December 2014. 224 cases of floating knee injuries gathered from the 34,480 lower extremities trauma files were studied, and the target information recorded. The injuries most frequently occurred in subjects between 16 and 35 years of age (60.71%), and in male subjects (85.71%). The most frequent mechanism of injury was traffic accident (92.85%). External fixation was the common type of treatment (82.14%) in emergency or as a definitive treatment. The treatment was performed within 24 h of the trauma. We performed a 36-month follow up with clinical examination, radiographs, assessing the complications, and using the Modified Cincinnati Rating System Questionnaire (MCRSQ) and the Karlström/Olerud Score (KOS) to evaluate the progression of the outcomes., Results: Early complications included 8 cases of compartment syndrome, 60 open fractures and 24 partially amputated limbs. A total amputation was performed in 3 patients. The most common late complication was heterotopic calcifications of the knee (n = 68, 30.6%). Good scores for MCRSQ and KOS were obtained only after patients were sent to a reference center for knee surgery., Conclusions: Our experience revealed that the complication rate associated with floatingknee injuries remains high, regardless of the performed treatment. Surgeons should focus on reducing complications while treating these severe injuries., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: After a trauma, exuberant tissue healing with fibrosis of the joint capsule can lead to posttraumatic joint stiffness (PTJS). Losartan and atorvastatin have both shown their antifibrotic effects in different organ systems., Objective: The purpose of this study was the evaluation of the influence of losartan and atorvastatin on the early development of joint contracture. In addition to joint angles, the change in myofibroblast numbers and the distribution of bone sialoprotein (BSP) were assessed., Study Design and Methods: In this randomized and blinded experimental study with 24 rats, losartan and atorvastatin were compared to a placebo. After an initial joint injury, rat knees were immobilized with a Kirschner wire. Rats received either losartan, atorvastatin or a placebo orally daily. After 14 days, joint angle measurements and histological assessments were performed., Results: Losartan increased the length of the inferior joint capsule. Joint angle and other capsule length measurements did not reveal significant differences between both drugs and the placebo. At cellular level both losartan and atorvastatin reduced the total number of myofibroblasts (losartan: 191±77, atorvastatin: 98±58, placebo: 319±113 per counting field, p <0.01) and the percentage area of myofibroblasts (losartan: 2.8±1.8% [ p <0.05], atorvastatin: 2.5±1.7% [ p <0.01], vs control [6.4±4%], respectively). BSP was detectable in equivalent amounts in the joint capsules of all groups with only a trend toward a reduction of the BSP-stained area by atorvastatin., Conclusion: Both atorvastatin and losartan reduced the number of myofibroblasts in the posterior knee joint capsule of rat knees 2 weeks after trauma and losartan increased the length of the inferior joint capsule. However, these changes at the cellular level did not translate an increase in range of motion of the rats´ knee joints during early contracture development., Competing Interests: Dr Andreas Baranowski reports grants from the Johannes Gutenberg-University Mainz and the German Society of Shoulder and Elbow Surgery (DVSE), during the conduct of the study. Dr Anja Klein reports grants from the German Society of Shoulder and Elbow Surgery (DVSE) and Inneruniversitäre Forschungsförderung Stufe I, during the conduct of the study. The authors report no other conflicts of interest in this work.

Objectives: To examine the metabolic profiles alterations of synovial fluids from anterior cruciate ligament- (ACL-) injured rabbit knees at early stage and analyze the correlation with T2 relaxation times of cartilage and meniscus., Methods: The right knees of 15 rabbits were selected for the construction of ACL injury models, whereas the contralateral knees served as control group. After 4 weeks, both knees were examined by MRI with quantitative T2 mapping sequence, and the T2 relaxation times of cartilage and meniscus were measured. Then, the synovial fluids were obtained from both knee capsules and performed liquid chromatography-mass spectrometry analysis (LC-MS)., Results: The T2 relaxation times of cartilage and meniscus in ACL-injured knees were significantly higher than those in control knees (Cartilage: 41.52 ± 2.98 ms vs 36.02 ± 2.71 ms, P < 0.001; Meniscus: 33.35 ± 3.57 ms vs 27.27 ± 2.10 ms, P < 0.001). Twenty-eight differential metabolites were identified based on a total of 1569 detected signatures between ACL-injured knees and control knees. These differential metabolites primarily implied perturbations in the fluxes of lipids and steroid-based compounds. The Linear regression analysis demonstrated satisfactory correlations between glycerophospholipid metabolism and T2 relaxation times of both cartilage and meniscus in ACL-injured knees (R 2 = 0.8204 and 0.8197, respectively)., Conclusion: ACL injury of rabbit knees resulted in elevated T2 relaxation times of cartilage and meniscus and perturbed metabolism of various lipids and steroids in synovial fluids, particularly glycerophospholipids. Glycerophospholipid metabolism related compounds could serve as potential biomarkers for early degenerative changes of cartilage and meniscus after ACL injury., Competing Interests: The authors have no potential conflict of interest.

Objective: The purpose of this study was to investigate the degree of standardized evaluation and reporting of cartilage lesion characteristics in high-impact clinical studies for symptomatic lesions of the knee. We hypothesized that there are significant inconsistencies in reporting these metrics across orthopedic literature., Design: A total of 113 clinical studies on articular cartilage restoration of the knee were identified from 6 high-impact orthopedic journals between 2011 and 2016. Full-text review was used to evaluate sources for details on study methodology and reporting on the following variables: primary procedure, location, size, grade, and morphology of cartilage lesions., Results: All studies reported on the type of primary cartilage procedure and precise lesion location(s). Approximately 99.1% reported lesion morphology (chondral, osteochondral, mixed). For lesion size, 32.7% of articles did not report how size was measured and 11.5% did not report units. The lesion sizing method was variable, as 27.4% used preoperative magnetic resonance imaging to measure/report lesion size, 31.0% used arthroscopy, and 8.8% used both. The majority of studies (83.2%) used area to report size, and 5.3% used diameter. Formal grading was not reported in 17.7% of studies. Only 54.8% of studies reported depth when sizing osteochondral defects., Conclusions: Recent literature on cartilage restoration provides adequate information on surgical technique, lesion location, and morphology. However, there is wide variation and incomplete reporting on lesion size, depth, and grading. Future clinical studies should include these important data in a consistent manner to facilitate comparison among surgical techniques.

Purpose: Synovial cyst of knee cruciate ligament (SCKCL) is a rare condition but can cause severe knee pain. The understanding of its etiology is relatively poor. This current study aimed to elucidate the pathogenesis of SCKCL based on a series of histo- and cytopathological examination., Methods: Ten SCKCL patients who underwent arthroscopy were enrolled, among five patients claimed past knee injury. Hematoxylin & eosin staining was conducted to the cyst wall tissue sections and Papanicolaou staining to the cyst fluid smear. Prussian blue staining was employed to both the wall section and fluid smear. Immumohistochemical staining for mesothelial cells (MC), epithelial cells (CK), vascular endothelial cells (CD31), monocytes (CD68), and hematogenous stem cells (CD117) were taken to elucidate the possible involvement of various cell types in the development of SCKCL., Results: No erythrocyte was discovered in the fluid; however, Prussian blue stained hemosiderin particles were found in the cyst wall and fluid, suggesting past hemorrhage in all patients. Abundant lymphocytes and plasmocytes were observed in the cyst wall and fluid. In addition, the cyst lining was infiltrated with abundant CD68(+) monocytes while only few MC(+) mesothelial cells were sporadically observed in four samples. The cyst submucosa was also diffused with abundant CD68(+) monocytes and proliferated capillaries stained with CD31. CD117-positve hematogenous stem cells were sporadically observed in eight specimens., Conclusion: Our findings provided evidence that SCKCL is not a mature synovial cyst but rather an inflammatory pseudo-cyst. It may have resulted from past minor hemorrhage and intra-ligament chronic inflammation.

Background: Osteochondral allograft transplantation (OCA) is a successful knee joint preservation technique; however, the effects of defect size and defect size:condyle ratio (DSCR) are poorly understood., Purpose: To quantify clinical outcomes of isolated OCA of the knee based on defect size and DSCR., Study Design: Cohort study; Level of evidence, 3., Methods: Data from patients who underwent OCA of the knee without major concomitant procedures by a single surgeon were analyzed at a minimum follow-up of 2 years. Osteochondral defect size was measured intraoperatively, and femoral condyle size was measured with preoperative imaging. Patient-reported outcomes, reoperations, and survival rates were analyzed per defect size and DSCR, comparing males and females and patients <40 and ≥40 years old., Results: Sixty-eight patients were included, of whom 57% were male (mean ± SD: age, 34.5 ± 10.3 years; follow-up, 5.2 ± 2.6 years). Mean osteochondral defect size and DSCR were 3.48 ± 1.72 cm 2 and 0.2 ± 0.1, respectively. Defect size was larger among males as compared with females (3.97 ± 1.71 cm 2 vs 2.81 ± 1.16 cm 2 , P = .005), while DSCRs were not significantly different between sexes ( P = .609). The cohort as a whole demonstrated improvements in the following scores: Lysholm, International Knee Documentation Committee, Knee injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, and 12-Item Short Form Health Survey Physical ( P < .05). There were 27 reoperations (39.7%) at a mean of 2.5 ± 1.92 years and 8 failures (11.8%) at a mean of 2.62 ± 1.3 years. Mean DCSR was higher among patients with graft failure (0.26 ± 0.20 vs 0.19 ± 0.07, P = .049). After stratification by age, failures among patients ≥40 years old were associated with a larger defect size (mean 5.37 ± 3.50 cm 2 vs 3.22 ± 1.32 cm 2 , P = .03) and higher DSCR (mean 0.30 ± 0.25 vs 0.19 ± 0.06, P = .05) when compared with nonfailures. Failures among patients <40 years old were not significantly associated with defect size or DSCR ( P > .05) as compared with nonfailures., Conclusion: Patients undergoing isolated OCA transplantation demonstrated significant clinical improvements and a graft survival of 88.2% at 5.2 years. Failures overall were associated with a larger DSCR, and failures among patients ≥40 years old with a larger DSCR and larger defect size. Increasing defect size among males was positively correlated with some improved outcomes, although this was not maintained in analysis of the DSCR, suggesting similar prognosis after OCA regardless of sex., Clinical Relevance: Failed osteochondral allografts are associated with larger defect sizes and defect:condyle ratios in this study, providing additional information to surgeons for appropriate patient consultation.

Knee injury is known as a frequently occurred damage related to sports, which may affect the function of cartilage. This study aims to explore whether Insulin-like growth factor 1 (IGF-1) and bone morphogenetic protein-7 (BMP-7)-modified bone-marrow mesenchymal stem cells (BMSCs) affect the repair of cartilage damage found in the knee. Primarily, BMSCs were treated with a series of pEGFP-C1, IGF-1, and BMP-7, followed by determination of IGF-1 and BMP-7 expression. A rabbit cartilage defect model was also established. Afterfward, cell morphology, viability, cartilage damage repair effect, and expression of collagen I and collagen II at the 6th and the 12th week were measured. BMSCs treated with pEGFP-C1/IGF-1, pEGFP-C1/BMP-7, and pEGFP-C1/BMP-7-IGF-1 exhibited elevated expression of BMP-7 and IGF-1. Besides, BMSCs in the P10 generation displayed decreased cell proliferation. Moreover, BMSCs treated with IGF-1, BMP-7, and IGF-1-BMP-7 showed reduced histological score and collagen I expression while elevated collagen II expression, as well as better repair effect, especially in those treated with IGF-1-BMP-7. Collectively, these results demonstrated a synergistic effect of IGF-1 and BMP-7 on the BMSC chondrogenic differentiation on the articular cartilage damage repair in the rabbit knees, highlighting its therapeutic potential for the treatment of articular cartilage damage., (© 2018 Wiley Periodicals, Inc.)

Purpose: The purpose of the study is to assess the stability of a dehydrated cartilage allograft combined with platelet-rich plasma sealed with fibrin glue within trochlear and medial femoral condyle (MFC) chondral defects in a cadaver knee model., Methods: Defects were made in the trochlea (20, 25, and 30 mm) and MFC (15, 20, and 25 mm) of 6 cadaver specimens. Allograft was applied utilizing 2 different techniques: (1) proud in which the fibrin level extends beyond surrounding cartilage and (2) recessed in which the fibrin level is even with or below the surrounding cartilage. The knees were cycled by using a continuous passive motion machine through a range of motion. Defects were assessed for superficial delamination and displacement of the allograft. This was quantified as the percentage of surface delamination and/or exposed bone. Comparisons were made with regard to defect size, location, and fill., Results: In both the MFC and trochlea, proud application resulted in an increased rate of fibrin delamination. In the trochlea, an average of 38% delamination was detected in the recessed 20-mm defect compared with 70% in the proud 30-mm defect (P < .05). This effect was increased with increasing defect size. In the MFC, mean delamination of 43% and 28% exposed bone was noticed in the proud 15-mm defect compared with 95% delamination and 71% exposed bone at 25 mm. In 82% of specimens, displacement and/or delamination occurred within the first 15 minutes of testing., Conclusions: Increased defect size in both the trochlea and femoral condyle, as well as a proud construct application, were associated with significant delamination and displacement of the allograft/fibrin construct., Clinical Relevance: Proud application of allograft increases the likelihood of fibrin delamination and graft displacement in both trochlear and MFC defects. This effect is increased with increasing defect size. These data may support limiting range of motion immediately after an allograft procedure., (Copyright © 2019 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: We described patellofemoral alignment and trochlear morphology at one and five years after anterior cruciate ligament reconstruction (ACLR), and evaluated the associations between alignment and trochlear morphology (at one year) and worsening patellofemoral osteoarthritis (OA) features by five years. We also evaluated the associations between alignment and morphology to self-reported pain and function (Knee injury and Osteoarthritis Outcome Score, KOOS) at five years., Materials and Methods: In this longitudinal observational study, we followed 73 participants (mean age 29[9] years, 40% women) from one- to five-years after ACLR. Using MRI, we measured alignment and morphology, and scored cartilage and bone marrow lesions at both time points. We used mixed effects and linear regression models to achieve our stated aims., Results: Greater lateral patella displacement increased risk of cartilage worsening (Odds Ratio [95% CI]: 1.09 [1.01, 1.16]); while less lateral tilt (0.91 [0.83, 0.99]) and greater trochlear angle (0.88 [0.77, 1.00]) were protective. Greater medial trochlear inclination increased risk of bone marrow lesion worsening (1.12 [1.04, 1.19]); while greater trochlear angle was protective (0.80 [0.67, 0.96]). Greater lateral displacement was associated with worse self-reported KOOS sport and recreation scores (β [95% CI]: -11.0 [-20.9, -1.2]) and quality of life scores (-10.5 [-20.4, -0.7])., Conclusions: Lateral displacement, lateral tilt, and morphology at 1 year post-ACLR altered the risk of worsening patellofemoral OA features four years later. Lateral displacement was the only measure associated with worse self-reported symptoms at five years. These findings may lead to novel treatment strategies for secondary prevention after ACLR., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Surgery or trauma may induce extensive arthrofibrosis around joints and tendon for the restrictive range of motion. Although some approaches were proposed, this problem is not solved satisfactorily. Extracorporeal shock wave therapy (ESWT) has been used for orthopedic, musculoskeletal, and fibrotic disorders. Whether it could prevent the formation of arthrofibrosis during the joint repair is unknown., Methods: Intra-articular adhesions were created in the right knee of the rabbit by cortical bone shaving and subsequent cast immobilization. Arthrofibrosis in the control and ESWT group was evaluated and compared at week 4., Results: Macroscopic score of arthrofibrosis and contracture angle of the control group are significantly higher. Histologically, the apparent gap between patella and tibia, loose connective tissue, and much less density of the blood vessel are found in the ESWT group., Conclusions: ESWT could noninvasively, effectively, and safely prevent the formation of arthrofibrosis during the knee repair., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Surgical transection of the anterior cruciate ligament (ACL) in the porcine model leads to posttraumatic osteoarthritis if left untreated. However, a recently developed surgical treatment, bridge-enhanced ACL repair, prevents further cartilage damage. Since the synovial fluid bathes all the intrinsic structures of knee, we reasoned that a comparative analysis of synovial fluid protein contents could help to better understand the observed chondroprotective effects of the bridge-enhanced ACL repair. We hypothesized that post-surgical changes in the synovial fluid proteome would be different in the untreated and repaired knees, and those changes would correlate with the degree of cartilage damage. Thirty adolescent Yucatan mini-pigs underwent unilateral ACL transection and were randomly assigned to either no further treatment (ACLT, n = 14) or bridge-enhanced ACL repair (BEAR, n = 16). We used an isotopically labeled high resolution LC MS/MS-based proteomics approach to analyze the protein profile of synovial fluid at 6 and 12 months after ACL transection in untreated and repaired porcine knees. A linear mixed effect model was used to compare the normalized protein abundance levels between the groups at each time point. Bivariate linear regression analyses were used to assess the correlations between the macroscopic cartilage damage (total lesion area) and normalized abundance levels of each of the identified secreted proteins. There were no significant differences in cartilage lesion area or quantitative abundance levels of the secreted proteins between the ACLT and BEAR groups at 6 months. However, by 12 months, greater cartilage damage was seen in the ACLT group compared to the BEAR group (p = 0.005). This damage was accompanied by differences in the abundance levels of secreted proteins, with higher levels of Vitamin K-dependent protein C (p = 0.001), and lower levels of Apolipoprotein A4 (p = 0.021) and Cartilage intermediate layer protein 1 (p = 0.049) in the ACLT group compared to the BEAR group. There were also group differences in the secreted proteins that significantly changed in abundance between 6 and 12 months in ACLT and BEAR knees. Increased concentration of Ig lambda-1 chain C regions and decreased concentration of Hemopexin, Clusterin, Coagulation factor 12 and Cartilage intermediate layer protein 1 were associated with greater cartilage lesion area. In general, ACLT knees had higher concentrations of pro-inflammatory proteins and lower concentrations of anti-inflammatory proteins than BEAR group. In addition, the ACLT group had a lower and declining synovial concentrations of CILP, in contrast to a consistently high abundance of CILP in repaired knees. These differences suggest that the knees treated with bridge-enhanced ACL repair may be maintaining an environment that is more protective of the extracellular matrix, a function which is not seen in the ACLT knees., Competing Interests: The authors have no competing interests directly related to this study. However, it should be noted that Dr. Murray holds several patents related to the BEAR surgical procedure, and that Drs. Murray and Fleming recently founded a company (Miach Orthopaedics Inc) to translate the BEAR surgical procedure to clinical use. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Patents: - Biologic replacement for fibrin clot (EP US WO Application US20040059416A1 & US WO Application US20020123805A1) - Device for mixing and delivering fluids for tissue repair (CA EP JP US WO Grant US8308681B2) - Methods and procedures for ligament repair (CA EP JP US WO Application WO2007087353A2) - Activation and delivery devices for therapeutic compositions(US Application US20120116300A1) - Methods and collagen products for tissue repair (US EP JP CA WO Application WO2008060361A2) - Biologic replacement for fibrin clot for intra-articular use (WO Application WO2000078370A1 & EP CA Application CA2377595A1) - Indirect method of articular tissue repair (CA WO Application CA3024196A1)

Meniscal tears are the most common orthopaedic injuries, with chronic lesions comprising up to 56% of cases. In these situations, no benefit with surgical treatment is observed. Thus, the purpose of this study was to investigate the effectiveness and safety of percutaneous intrameniscal platelet rich plasma (PRP) application to complement repair of a chronic meniscal lesion. This single centre, prospective, randomized, double-blind, placebo-controlled study included 72 patients. All subjects underwent meniscal trephination with or without concomitant PRP injection. Meniscal non-union observed in magnetic resonance arthrography or arthroscopy were considered as failures. Patient related outcome measures (PROMs) were assessed. The failure rate was significantly higher in the control group than in the PRP augmented group (70% vs. 48%, P = 0.04). Kaplan-Meyer analysis for arthroscopy-free survival showed significant reduction in the number of performed arthroscopies in the PRP augmented group. A notably higher percentage of patients treated with PRP achieved minimal clinically significant difference in visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) symptom scores. Our trial indicates that percutaneous meniscal trephination augmented with PRP results in a significant improvement in the rate of chronic meniscal tear healing and this procedure decreases the necessity for arthroscopy in the future (8% vs. 28%, P = 0.032).

The human meniscus plays a crucial role for transmission and distribution of load across the knee, as well as shock absorption, joint stability, lubrication, and congruity. The aim of this study was to compare the complex geometry, and unique ultrastructure and tissue composition of the meniscus in healthy (control) and pathological conditions to provide understanding of structural changes that could be helpful in the future design of targetted therapies and improvement of treatment indications. We analyzed meniscus samples collected from 3 healthy multi-organ donors (median age, 66 years), 5 patients with traumatic meniscal tear (median age, 41 years) and 3 patients undergoing total knee replacement (TKR) for end-stage osteoarthritis (OA) (median age, 72 years). We evaluated the extracellular matrix (ECM) organization, the appearance and distribution of areas of calcification, and modifications of cellular organization and structure by electron microscopy and histology. The ECM structure was similar in specimens from traumatic meniscus tears compared to those from patients with late-stage OA, showing disorganization of collagen fibers and increased proteoglycan content. Cells of healthy menisci showed mainly diffuse chromatin and well preserved organelles. Both in traumatic and in OA menisci, we observed increased chromatin condensation, organelle degeneration, and cytoplasmic vacuolization, a portion of which contained markers of autophagic vacuoles. Areas of calcification were also observed in both traumatic and OA menisci, as well as apoptotic-like features that were particularly prominent in traumatic meniscal tear samples. We conclude that meniscal tissue from patients with traumatic meniscal injury demonstrate pathological alterations characteristic of tissue from older patients undergoing TKR, suggesting that they have high susceptibility to develop OA.

The aim of this PRISMA review was to assess whether the CMI and Actifit scaffolds, when used in clinical practice, improve clinical outcomes and demonstrate the ideal biological and biomechanical properties of scaffolds: being chondroprotective, porous, resorbable, able to mature and promote regeneration of tissue. This was done by only including studies that assessed clinical outcome and used a scale to assess both integrity of the scaffold and its effects on articular cartilage via MRI. A search was performed on PubMed, EMBASE, Scopus and clinicaltrials.gov. 2457 articles were screened, from which eight studies were selected: four used Actifit, three used CMI and one compared the two. All studies reported significant improvement in at least one clinical outcome compared to baseline. Some studies suggested that the scaffolds appeared to show porosity, mature, resorb and/or have possible chondroprotective effects, as assessed by MRI. The evidence for clinical translation is limited by differences in study methodology and small sample sizes, but is promising in terms of improving clinical outcomes in the short to mid-term. Higher level evidence, with MRI and histological evaluation of the scaffold and articular cartilage, is now needed to further determine whether these scaffolds exhibit these useful properties.