Diagnostic Accuracy of MRI in Knee Meniscus Tear and ACL Injury.

Objective: Knee injuries are very common and may lead to other secondary injuries if effective treatment is lacking. In addition to standardized physical examination, magnetic resonance imaging (MRI) is sometimes considered an aid in the diagnosis of knee trauma. In order to have a more accurate diagnosis of knee injuries, we compared MRI with arthroscopic findings in this study to evaluate the diagnostic accuracy of MRI for meniscal tears and anterior cruciate ligament injuries of the knee. Methods: One hundred and ten patients with suspected meniscal tears and anterior cruciate ligament injuries of the knee who were admitted to our hospital from June 2020 to June 2022 were selected as study subjects, and the clinical data of the patients were retrospectively analyzed. All patients underwent MRI for preoperative diagnosis, and the sensitivity, specificity, MRI findings, and confirmation of diagnosis were compared and analyzed, and the accuracy of MRI in diagnosing meniscal tears and ACL injuries of the knee was analyzed. Results: The mean ACL angle was (98.0 ± 5.4) in the MRI group and (118.0 ± 6.8) in the arthroscopic group, the difference between the two groups was statistically significant P < .05. The mean L/H value of the ACL was (2.12 ± 0.38) in the MRI group and (1.81 ± 0.19) in the arthroscopic group, which was statistically different between the two groups (P < .05). Among the patients, 68 meniscal injuries were found in the MRI examination, including 45 cases of knee meniscal tears and 23 cases of anterior cruciate ligament injuries. The sensitivity, specificity, positive and negative predictive values, agreement rate, kappa value, and Youden index of MRI in diagnosing meniscal tears and ACL injuries were all high. Conclusions: In terms of sensitivity and accuracy, MRI is an excellent imaging technique for the diagnosis of meniscal tears and anterior cruciate ligament injuries of the knee.

Sports rehabilitation in athletes with meniscal lesions based on electroacupuncture associated with sports therapy / Reabilitação esportiva de atletas com lesão meniscal baseada em eletroacupuntura combinada à terapia esportiva / Rehabilitación deportiva de atletas con lesión meniscal basada en electroacupuntura combinada con la terapia deportiva

ABSTRACT Introduction: Meniscal injury is a common condition that can lead to disability due to pain and proprioceptive failure, requiring immediate attention. Combination therapies involve advanced approaches aiming to accelerate rehabilitation in athletes, and electroacupuncture presents therapeutic benefits, although there is still no evidence of its combination with sports therapy. Objective: This paper analyzes the performance of sports rehabilitation in athletes with meniscal lesions using electroacupuncture combined with sports therapy. Methods: The intervention in the control group was based on a traditional range of motion work, muscle strength, proprioceptive training, and other exercise therapies, while the experimental group received a 30 min electro-acupuncture protocol three times a week for four consecutive weeks. The surrogate data (gender, age, disease course, location) are the same. Before treatment, joint activity, muscle strength, total joint scale score of the LYSHOLM questionnaire, and other observational indices were measured during the 6th and 12th week of treatment. The non-parametric statistical method and T-test were used to analyze the changes of each index before and after treatment. After 12 weeks of treatment, the difference between the experimental group and the combination before treatment was significant. Results: The treatment effect of the experimental group was significantly better than the control group. Conclusion: The effect of sports rehabilitation of athletes with meniscus injury based on electroacupuncture combined with sports therapy showed high resolutive application value, indicating an alternative for non-surgical treatment in knee meniscus injuries. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A lesão meniscal é um acometimento comum que pode gerar incapacitação por dor e falha proprioceptiva, exigindo atenção imediata. Terapias combinadas envolvem abordagens avançadas com o objetivo de acelerar a reabilitação nos atletas, e a eletroacupuntura apresenta benefícios terapêuticos, embora ainda não possua evidencias de sua combinação com a terapia esportiva. Objetivo: Analisar o desempenho da reabilitação esportiva em atletas com lesão meniscal utilizando eletroacupuntura combinada à terapia esportiva. Métodos: A intervenção no grupo controle baseou-se no trabalho tradicional de amplitude de movimento, força muscular, treinamento proprioceptivo e outros tipos de terapias de exercício enquanto que ao grupo experimental foi adicionado um protocolo de eletro-acupuntura de 30 minutos de duração, 3 vezes por semana durante 4 semanas consecutivas. Os dados de substituição (sexo, idade, curso de doença, localização) são basicamente os mesmos. Antes do tratamento, a atividade articular, a força muscular, o escore total da escala articular do questionário LYSHOLM e outros índices de observação foram medidos na 6ª e 12ª semana do tratamento. O método estatístico não paramétrico e teste-T foram utilizados para analisar as alterações de cada índice antes e depois do tratamento. Após 12 semanas de tratamento, a diferença entre o grupo experimental e a combinação antes do tratamento foi significativa. Resultados: O efeito de tratamento do grupo experimental foi significativamente melhor do que o grupo controle. Conclusão: O efeito de reabilitação esportiva de atletas com lesão meniscal baseada em eletroacupuntura combinada à terapia esportiva demonstrou alto valor de aplicação resolutiva, indicada como alternativa para o tratamento não cirúrgico em lesões no menisco do joelho. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

Resumen Introducción: La lesión meniscal es una lesión común que puede causar incapacidad por dolor y fallo propioceptivo, requiriendo atención inmediata. Las terapias combinadas implican enfoques avanzados con el objetivo de acelerar la rehabilitación en los deportistas, y la electroacupuntura presenta beneficios terapéuticos, aunque todavía no hay pruebas de su combinación con la terapia deportiva. Objetivo: Analizar el rendimiento de la rehabilitación deportiva en atletas con lesión meniscal utilizando electroacupuntura combinada con la terapia deportiva. Métodos: La intervención en el grupo de control se basó en el trabajo tradicional de amplitud de movimiento, fuerza muscular, entrenamiento propioceptivo y otros tipos de terapias de ejercicio, mientras que al grupo experimental se le añadió un protocolo de electroacupuntura de 30 minutos de duración, 3 veces a la semana durante 4 semanas consecutivas. Los datos sustitutivos (sexo, edad, evolución de la enfermedad, localización) son básicamente los mismos. Antes del tratamiento, se midieron la actividad articular, la fuerza muscular, la puntuación total de la escala articular del cuestionario LYSHOLM y otros índices de observación en la 6ª y 12ª semana de tratamiento. Se utilizó el método estadístico no paramétrico y la prueba T para analizar los cambios de cada índice antes y después del tratamiento. Tras 12 semanas de tratamiento, la diferencia entre el grupo experimental y la combinación antes del tratamiento era significativa. Resultados: El efecto del tratamiento del grupo experimental fue significativamente mejor que el del grupo de control. Conclusión: El efecto de la rehabilitación deportiva de atletas con lesión de menisco basada en la electroacupuntura combinada con la terapia deportiva mostró un alto valor de aplicación resolutiva, indicada como alternativa de tratamiento no quirúrgico en las lesiones de menisco de rodilla. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Rehabilitation and Return to Play Following Meniscus Repair.

Injuries to the meniscus, particularly tears, can have significant negative impacts on pain, function, and quality of life. Preservation of the meniscus is favorable, especially in the athletic and active populations. While first line treatment is often nonoperative in nature, recalcitrant, and more complex tears, typically require surgery. Meniscus repair rates have increased significantly during the last 2 decades as surgical techniques and postoperative outcomes have improved. Longer postoperative timeframes are to be expected when compared with menisectomy, however, accelerated programs have demonstrated favorable outcomes. Rehabilitation and return to play guidelines should reflect the intricacies of the tear type and repair procedure. Close communication with the surgeon is a vital component to optimize patient outcomes. Further, the patient's goals and expected level of return to function, or sport, must be taken into account for a rehabilitation program to be fully successful.

A predictive model with radiographic signs can be a useful supplementary diagnostic tool for complete discoid lateral meniscus in adults.

PURPOSE: To investigate the diagnostic accuracy of radiographic signs for complete discoid lateral meniscus and whether a predictive model combining the radiographic signs can improve its diagnostic accuracy in adults. METHODS: A total of adult 119 knees with complete discoid lateral meniscus confirmed by arthroscopy and 119 age- and sex-matched knees with normal meniscus were included. The radiographic signs of lateral joint space, fibular head height, lateral tibial spine height, lateral tibial plateau obliquity, lateral femoral condyle squaring, lateral tibial plateau cupping, lateral femoral condyle notching, and the condylar cut-off sign were evaluated. The receiver-operating characteristic (ROC) curves and area under the curve (AUC) were evaluated for best accuracy. A prediction model was developed by multivariable regression with generalized estimating models, and was validated using data from 111 knees of children with complete discoid lateral meniscus and 111 normal controls. RESULTS: The fibular head height, lateral joint space, lateral tibial plateau obliquity, and the condylar cut-off sign were significantly different between the complete discoid lateral meniscus and the normal groups (p < 0.05). Among the four radiographic signs, the fibular head height showed the highest accuracy with 78.9% sensitivity and 57.3% specificity. The prediction models developed by logistic regression showed significantly improved accuracy for complete discoid lateral meniscus compared to the fibular head height (sensitivity: 69.8%, specificity: 82.9%, p = 0.001). For validation, the AUC of children seemed to be larger than that of adults, which indicated that the prediction models could be applied for children to detect complete discoid lateral meniscus. CONCLUSION: Among several radiographic signs, the fibular head height can be used as a screening tool for complete discoid lateral meniscus. The prediction models combined with lateral joint space, fibular head height, lateral tibial plateau obliquity, and/or the condylar cut-off sign yielded a much higher diagnostic value than each radiographic sign. Therefore, fibular head height and prediction models combined with radiographic signs can provide improved diagnostic value for complete discoid lateral meniscus. LEVEL OF EVIDENCE: III.

Isolated Meniscus Tears in Adolescent Patients Treated with Platelet-Rich Plasma Intra-articular Injections: 3-Month Clinical Outcome.

OBJECTIVES: Meniscus repair is a challenge for a practitioner, as an injured meniscus can lead to osteoarthritic joint changes with a greatly disabling outcome. Platelet-rich plasma has been regarded as a promising therapy to help induce healing. The purpose of the study is to clinically assess the effectiveness of PRP treatment in adolescents with meniscal lesions. METHODS: This retrospective study analyzed 30 patients with meniscal tears, aged 12 to 17 years, who had documented MRI meniscal lesion and persistent knee pain. In order to evaluate the outcome, the Lysholm knee scoring scale and numerical rating scale were used before injection and 3 months after treatment. RESULTS: Patients had a mean age of 13.93 years, 70% girls and 30% boys. The most affected was the medial meniscus. The mean value before injection on the numerical rating scale (NRS) of pain was 7.73, after the treatment being of 2.0. After treatment, 76.7% of the patients had "excellent" and "good" outcomes, while before injection, just 3% of the patients had a "good" score. CONCLUSIONS: Platelet-rich plasma treatment can be effective in improving the clinical outcomes of adolescent patients with meniscus tears, for whom conservative management and physical therapy have failed to achieve pain relief.

Predictive validity of radiographic signs of complete discoid lateral meniscus in children using machine learning techniques.

The diagnostic utility of radiographic signs of complete discoid lateral meniscus remains controversial. This study aimed to investigate the diagnostic accuracy and determine which sign is most reliably detects the presence of a complete discoid lateral meniscus in children. A total of 141 knees (age 7-16) with complete discoid lateral meniscus and 141 age- and sex-matched knees with normal meniscus were included. The following radiographic signs were evaluated: lateral joint (LJ) space, fibular head (FH) height, lateral tibial spine (LTS) height, lateral tibial plateau (LTP) obliquity, lateral femoral condyle (LFC) squaring, LTP cupping, LFC notching, and prominence ratio of the femoral condyle. Prediction models were constructed using logistic regressions, decision trees, and random forest analyses. Receiver operating characteristic curves and area under the curve (AUC) were estimated to compare the diagnostic accuracy of the radiographic signs and model fit. The random forest model yielded the best diagnostic accuracy (AUC: 0.909), with 86.5% sensitivity and 82.2% specificity. LJ space height, FH height, and prominence ratio showed statistically large AUC compared with LTS height and LTP obliquity (P < .05 in all). The cut-off values for diagnosing discoid meniscus to be <12.55 mm for FH height, <0.804 for prominence ratio, and >6.6 mm for LJ space height when using the random forest model. On the basis of the results of this study, in clinical practice, LJ space height, FH height and prominence ratio could be easily used as supplementary tools for complete discoid lateral meniscus in children.

Terapias biológicas en artroscopía de rodilla. De las ciencias básicas a la aplicación clínica / Biological therapies in knee arthroscopy. From basic sciences to clinical application

Las estructuras intraarticulares, como el cartílago, el ligamento cruzado anterior (LCA) y los meniscos tienen un potencial de cicatrización limitado una vez que se lesionan. Un mayor conocimiento de las ciencias básicas y el advenimiento de las terapias biológicas han creado un gran interés en la utilización de diferentes estrategias de aumentación, cuyo objetivo es facilitar el proceso de cicatrización de dichas estructuras de la rodilla. Nuestro propósito es presentar una revisión de los conceptos actuales sobre las terapias biológicas en artroscopía de rodilla.Se realizó una revisión de la literatura que incluyó búsquedas en las bases de datos PubMed, Medline, Embase y Cochrane, utilizando las siguientes palabras clave: terapias biológicas, lesión del LCA, lesión meniscal, lesión del cartílago articular, PRP, BMAC, Bio-Ortopedia y Ortobiológicos.Se ha reportado que la utilización de técnicas biológicas de aumentación, incluidas el plasma rico en plaquetas (PRP), la médula ósea concentrada (BMAC) y otras terapias celulares para lesiones del cartílago articular, del LCA y de los meniscos podría facilitar el proceso de cicatrización con resultados clínicos prometedores.Podemos concluir que, efectivamente, existe un creciente interés en la utilización de terapias biológicas en las lesiones de rodilla con resultados clínicos heterogéneos, pero promisorios. Se necesitan estudios adicionales, randomizados, prospectivos, controlados y comparativos para determinar la eficacia real de las diferentes estrategias de aumento biológico en el entorno clínico

Intra-articular structures such as articular cartilage, anterior cruciate ligament (ACL), and menisci have limited healing potential after injury. The greater knowledge of the basic sciences and the advent of biological therapies have created a great interest in the use of different augmentation strategies, whose objective is to facilitate the healing process of these knee structures.To present a current concept review on the use of biological therapies in knee arthroscopy.A literature review was performed that included searches of the PubMed, Medline, Embase and Cochrane databases using the following keywords: Biological therapies, ACL tears, meniscal tears, articular cartilage injury, PRP, BMAC, Bio-Orthopaedics and Orthobiologics.It has been reported that the use of biological augmentation techniques, including Platelet rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and other cellular therapies for injuries to articular cartilage, ACL, and menisci, could facilitate the healing process with promising clinical results.There is a growing interest in the use of biological therapies in knee injuries with heterogeneous but promising clinical results. Additional, randomized, prospective, controlled, and comparative studies are needed to determine the true efficacy of different biological augmentation strategies in the clinical setting

Factors associated with bilateral discoid lateral meniscus tear in patients with symptomatic discoid lateral meniscus tear using MRI and X-ray.

BACKGROUND: The incidence of bilateral discoid lateral meniscus (DLM) is as high as 73 to 85%, and associated contralateral meniscus tears ranged from 4 to 33% in symptomatic surgical DLM. The goal of the study was analyzing the factors that predict contralateral presence and tearing of DLM in patients who underwent surgery for symptomatic DLM. Our hypothesis was that there is a significant correlation between operative DLM properties and the incidence of bilateral DLM with associated contralateral meniscus tears. These properties include tear patterns, younger patient age, and characteristic X-ray findings. PATIENTS AND METHODS: This prospective study included 76 patients who underwent arthroscopic surgery for symptomatic DLM. The contralateral knees were evaluated with X-ray and MRI. Based on the MRI findings, DLM was categorized into three types, and tear patterns were analyzed. The characteristic X-ray findings were evaluated as follows: (1) high fibular head, (2) squared-off appearance of the lateral femoral condyle, (3) cupping of the lateral tibial plateau, (4) widened femorotibial joint space, (5) hypoplasia of the lateral intercondylar spine, (6) notching of the LFC. The number of characteristic X-ray findings (0/1/more than 2) was noted. Binary logistic analysis was performed to find the factors that predict the presence and tear of contralateral DLM. RESULTS: MRI of contralateral knees revealed 43 cases (57%) of complete DLM, 25 cases (33%) of incomplete DLM, and 8 cases (11%) of normal meniscus. Meniscus tears were found in 29 cases (38%) in the contralateral knee. X-ray of the contralateral knee revealed that 27 patients (36%) had one and 24 patients (32%) had two or more characteristic X-ray findings. On logistic regression analysis, the associations between contralateral knee meniscal tear and the presence of one or more than two characteristic X-ray findings were statistically significant (OR: 16.5, p=0.028; OR: 264.0, p=0.000, respectively). DISCUSSION: The number of characteristic X-ray findings in the contralateral knee is a significant predictive factor for contralateral DLM type and/or tear. Symptomatic DLM patients with characteristic X-ray findings should be carefully evaluated for contralateral DLM and meniscal tears. LEVEL OF EVIDENCE: III, prospective diagnostic study of consecutive patients.

Effect of dose and release rate of CTGF and TGFß3 on avascular meniscus healing.

Meniscus tears in the avascular region rarely functionally heal due to poor intrinsic healing capacity, frequently resulting in tear propagation, followed by meniscus deterioration. Recently, we have reported that time-controlled application of connective tissue growth factor (CTGF) and transforming tissue growth factor ß3 (TGFß3) significantly improved healing of avascular meniscus tears by inducing recruitment and step-wise fibrocartilaginous differentiation of mesenchymal stem/progenitor cells (MSCs). In this study, we investigated effects of the dose of CTGF and the release rate of TGFß3 on avascular meniscus healing in our existing explant model. Our hypothesis was that dose and release rate of CTGF and TGFß3 are contributing factors for functional outcome in avascular meniscus healing by stem cell recruitment. Low (100 ng/ml) and high (1,000 ng/ml) doses of CTGF as well as fast (0.46 ± 0.2 ng/day) and slow (0.29 ± 0.1 ng/day) release rates of TGFß3 were applied to our established meniscus explant model for meniscus tears in the inner-third avascular region. The release rate of TGFß3 was controlled by varying compositions of poly(lactic-co-glycolic acids) (PLGA) microspheres. The meniscus explants were then cultured for 8 weeks on top of mesenchymal stem/progenitor cells (MSCs). Among the tested combinations, we found that a high CTGF dose and slow TGFß3 release are most effective for integrated healing of avascular meniscus, demonstrating improvements in alignment of collagen fibers, fibrocartilaginous matrix elaboration and mechanical properties. This study may represent an important step toward the development of a regenerative therapy to improve healing of avascular meniscus tears by stem cell recruitment. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1555-1562, 2019.

Comparison of T2* mapping between regular echo time and ultrashort echo time with 3D cones at 3 tesla for knee meniscus.

The objectives of this study were to compare the ultrashort T2* relaxation time with the T2* relaxation time using the 3 dimensional (3D) cones sequence in 3 groups of patients with normal, degenerated, and torn knee menisci, and to demonstrate the additional effect of the ultrashort echo time (UTE) signal intensity.Following institutional review board approval, 42 knee magnetic resonance imaging (MRI) scans of 42 patients who presented with knee pain and underwent knee MRIs, with the 3D Cones of UTE sequence (minimum TEs: 32 µs) and a 3T MRI scanner (Discovery 750, GE Healthcare, Waukesha, WI), were analyzed. The enrolled patients were classified into 3 subgroups:normal meniscus on conventional MRI, with no positive meniscus-related physical examination in medical records;meniscal degeneration with signal changes on conventional MRI; andmeniscal tear.For the quantitative assessment, the mean values inside user-drawn regions of interest (ROIs) of the medial menisci were drawn on UTE T2* map and T2* map. For statistical analyses, 1-way analysis of variance (ANOVA) with post-hoc analysis using the Tukey HSD test was conducted to compare groups, and effect size was used to compare the discrimination power.The ultrashort T2* relaxation times were higher in patients with meniscal tear than in those with normal and degeneration groups (P <.05, respectively) whereas T2* relaxation times were not statistically significantly different. The ultrashort T2* relaxation times showed higher effect sizes than the T2* times between tear and normal/degeneration.The ultrashort T2* relaxation times showed better delineation of meniscal degeneration or tears than T2* relaxation times. The ultrashort T2* relaxation times could be more sensitive at differentiating between normal and pathologic meniscal conditions in patients.

The TeMPO trial (treatment of meniscal tears in osteoarthritis): rationale and design features for a four arm randomized controlled clinical trial.

BACKGROUND: Meniscal tears often accompany knee osteoarthritis, a disabling condition affecting 14 million individuals in the United States. While several randomized controlled trials have compared physical therapy to surgery for individuals with knee pain, meniscal tear, and osteoarthritic changes (determined via radiographs or magnetic resonance imaging), no trial has evaluated the efficacy of physical therapy alone in these subjects. METHODS: The Treatment of Meniscal Tear in Osteoarthritis (TeMPO) Trial is a four-arm multi-center randomized controlled clinical trial designed to establish the comparative efficacy of two in-clinic physical therapy interventions (one focused on strengthening and one containing placebo) and two protocolized home exercise programs. DISCUSSION: The goal of this paper is to present the rationale behind TeMPO and describe the study design and implementation strategies, focusing on methodologic and clinical challenges. TRIAL REGISTRATION: The TeMPO Trial was first registered at clinicaltrials.gov with registration No. NCT03059004 . on February 14, 2017.

A 12-week supervised exercise therapy program for young adults with a meniscal tear: Program development and feasibility study.

OBJECTIVE: To describe the development and feasibility of an exercise therapy program for treatment of young adults (18-40 years of age) with a meniscal tear. METHODS: Researchers and experienced physical therapists developed a 12-week supervised neuromuscular and strengthening exercise therapy program based on clinical expertise and available evidence. Six patients (age range 22-39 years) considered eligible for meniscal surgery by an orthopedic surgeon underwent the program. Patients completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) and evaluated the program during a semi-structured qualitative interview. Feedback from patients was included to finalize the exercise therapy program. RESULTS: Median improvements (Range) in KOOS subscales were 15 (0-33) for Pain, 11 (-11 to 50) for Symptoms, 16 (3-37) for Function in daily living, 23 (10-45) for Function in sport and recreation, and 9 (-6 to 31) for Quality of life. The patients found the program relevant and effective with only a few short-lasting adverse events and important clinical improvements after four to ten weeks. Physical therapist supervision was considered important. No patients wanted surgery up to 6 month after the exercise therapy program. CONCLUSION: A neuromuscular and strengthening exercise therapy program was feasible and showed important improvement in a small group of young adults with meniscal tears.

Bilateral discoid medial meniscus associated with meniscal tears and hypoplasia of the medial femoral condyle: A case report.

RATIONALE: Bilateral discoid medial menisci is an extremely rare abnormality of the knee joint. The presence of a discoid medial meniscus has been associated with magnetic resonance imaging (MRI) and radiographic changes in the tibial region, such as cupping of the medial tibial plateau and tibial physis collapse. While discoid medial meniscal tears with hypoplasia of the femoral medial condyles have not been previously reported. Herein, we report a case of bilateral discoid medial menisci associated with meniscal tears and femoral bone changes. PATIENT CONCERNS: A 28-year-old man presented with left knee pain and restricted range of motion; the right knee was asymptomatic. DIAGNOSES: Based on radiographic and MRI findings, he was diagnosed with bilateral discoid medial meniscal tears. INTERVENTIONS: Partial meniscectomy and reshaping were performed for the torn discoid medial meniscus of the left knee only. OUTCOMES: MRI revealed short, flattened femoral medial condyles in the coronal and sagittal planes, and hypoplasia of the femoral medial condyles in the axial plane; these findings were confirmed arthroscopically in the left knee. The patient had a satisfactory results at the 12-month follow-up. LESSONS: This case indicates a potential link between discoid medial menisci and hypoplasia of the femoral medial condyle. We recommend preservation of the discoid medial meniscus in asymptomatic patients, while arthroscopic partial meniscectomy and reshaping is recommended in symptomatic patients.

Deletion of 12/15-lipoxygenase accelerates the development of aging-associated and instability-induced osteoarthritis.

OBJECTIVE: 12/15-Lipoxygenase (12/15-LOX) catalyzes the generation of various anti-inflammatory lipid mediators, and has been implicated in several inflammatory and degenerative diseases. However, there is currently no evidence that 12/15-LOX has a role in osteoarthritis (OA). The aim of this study was to investigate the role of 12/15-LOX in the pathogenesis of OA. METHODS: The development of aging-associated and destabilization of the medial meniscus (DMM)-induced OA were compared in 12/15-LOX-deficient (12/15-LOX-/-) and wild-type (WT) mice. The extent of cartilage damage was evaluated by histology. The expression of OA markers was evaluated by immunohistochemistry and RT-PCR. Cartilage explants were stimulated with IL-1α in the absence or presence of the 12/15-LOX metabolites, 15-hydroxyeicosatetraenoic acids (15-HETE), 13-hydroxyoctadecadienoic acid (13-HODE) or lipoxin A4 (LXA4), and the levels of matrix metalloproteinases-13 (MMP-13), Nitric oxide (NO) and prostaglandin E2 (PGE2) were determined. The effect of LXA4 on the progression of OA was evaluated in wild type (WT) mice. RESULTS: The expression of 12/15-LOX in cartilage increased during the progression of DMM-induced OA and with aging in WT mice. Cartilage degeneration was more severe in 12/15-LOX-/- mice compared to WT mice in both models of OA, and this was associated with increased expression of MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs, aggrecanases (ADAMTS5), inducible NO synthases (iNOS), and mPGES-1. Treatment of cartilage explants with 12/15-LOX metabolites, suppressed IL-1α-induced production of MMP-13, NO and PGE2, with LXA4 being the most potent. Intra-peritoneal injection of LXA4 reduced the severity of DMM-induced cartilage degradation. CONCLUSIONS: These data suggest an important role of 12/15-LOX in the pathogenesis of OA. They also suggest that activation of this pathway may provide a novel strategy for prevention and treatment of OA.

Conservative management of a traumatic meniscal injury utilising osteopathy and exercise rehabilitation: A case report.

Meniscal injury is one of the most common knee soft tissue injuries, commonly affecting young athletes and an older, degenerative population. Treatment largely depends on the type and extent of the injury with arthroscopic repair or meniscectomy being mainstays. Although non-surgical approaches have been described, there is no published literature regarding a combination of indirect osteopathic techniques and rehabilitation in the management of these injuries. The current case report follows a 20-year-old male presenting with a 5-day history of acute knee pain, following trauma during an Australian Rules Football (AFL) match. An 8-week management plan of indirect osteopathic techniques and a tailored rehabilitation program was implemented. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Lower Extremity Functional Scale (LEFS) questionnaires were utilised to measure outcomes. After the 8-week treatment and rehabilitation program, the patient had exceeded the minimum detectable change score for all outcome measures. This case report suggests that osteopathic manipulative treatment and rehabilitation may be an alternative, non-surgical approach in the management of post-traumatic meniscal injuries.

Nerve growth factor inhibition with tanezumab influences weight-bearing and subsequent cartilage damage in the rat medial meniscal tear model.

OBJECTIVE: To investigate whether the effects of nerve growth factor (NGF) inhibition with tanezumab on rats with medial meniscal tear (MMT) effectively model rapidly progressive osteoarthritis (RPOA) observed in clinical trials. METHODS: Male Lewis rats underwent MMT surgery and were treated weekly with tanezumab (0.1, 1 or 10 mg/kg), isotype control or vehicle for 7, 14 or 28 days. Gait deficiency was measured to assess weight-bearing on the operated limb. Joint damage was assessed via histopathology. A second arm, delayed onset of treatment (starting 3-8 weeks after MMT surgery) was used to control for analgesia early in the disease process. A third arm, mid-tibial amputation, evaluated the dependency of the model on weight-bearing. RESULTS: Gait deficiency in untreated rats was present 3-7 days after MMT surgery, with a return to normal weight-bearing by days 14-28. Prophylactic treatment with tanezumab prevented gait deficiency and resulted in more severe cartilage damage. When onset of treatment with tanezumab was delayed to 3-8 weeks after MMT surgery, there was no increase in cartilage damage. Mid-tibial amputation completely prevented cartilage damage in untreated MMT rats. CONCLUSIONS: These data suggest that analgesia due to NGF inhibition during the acute injury phase is responsible for increased voluntary weight-bearing and subsequent cartilage damage in the rat MMT model. This model failed to replicate the hypotrophic bone response observed in tanezumab-treated patients with RPOA.

Identification and pharmacological characterization of a novel inhibitor of autotaxin in rodent models of joint pain.

OBJECTIVE: Autotaxin is a secreted lysophospholipase that mediates the conversion of lysophosphatidyl choline (LPC) to lysophosphatidic acid (LPA), a bioactive lipid mediator. Autotaxin levels in plasma and synovial fluid correlate with disease severity in patients with knee osteoarthritis (OA). The goal of this study was to develop and characterize a novel small molecule inhibitor of autotaxin to inhibit LPA production in vivo and determine its efficacy in animal models of musculoskeletal pain. DESIGN: Compound libraries were screened using an LPC coupled enzyme assay that measures the amount of choline released from LPC by the action of autotaxin. Hits from this assay were tested in a plasma assay to assess inhibition of endogenous plasma autotaxin and subsequently tested for their ability to lower plasma LPA levels upon oral dosing of rats. The best compounds were then tested in animal models of musculoskeletal pain. RESULTS: Compound screening led to the identification of compounds with nanomolar potency for inhibition of autotaxin activity. Studies in rats demonstrated a good correlation between compound exposure levels and a decrease in LPA levels in plasma. The leading molecule (compound-1) resulted in a dose dependent decrease in joint pain in the mono-sodium iodoacetate (MIA) and meniscal tear models and a decrease in bone fracture pain in the osteotomy model in rats. CONCLUSION: We have identified and characterized a novel small molecule inhibitor of autotaxin and demonstrated its efficacy in animal models of musculoskeletal pain. The inhibitor has the potential to serve as an analgesic for human OA and bone fracture.

Sulfasalazine attenuates ACL transection and medial menisectomy-induced cartilage destruction by inhibition of cystine/glutamate antiporter.

We had previously demonstrated that excitatory amino acid glutamate plays a role in the progression and severity of knee osteoarthritis (OA), and early hyaluronic acid injection attenuates the OA progression by attenuation of knee joint glutamate level, which was also related to the cystine/glutamate antiporter system X (system XC-) expression. System XC- uptakes cystine into chondrocytes for glutathione (GSH) synthesis, but the role of system XC- in OA is rarely addressed. Sulfasalazine (SSZ) is a system XC- inhibitor; SSZ was applied intra-articularly to study the function of system XC- in the development of OA in rats subjected to anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx). Moerover, the system XC- activator N-acetylcysteine (NAC) was also applied to verify the role of system XC-. The intra-articular injection of SSZ significantly attenuated knee swelling and cartilage destruction in the knees of ACLT + MMx rats and this effect was blocked by NAC. The results showed that inhibition of system XC- function can attenuate ACLT + MMx-induced cartilage destruction. In the present study, system XC- inhibitor SSZ was shown to reduce glutamate content in synovial fluid and GSH in chondrocytes. It was also showed SSZ could attenuate ACLT + MMx-induced cartilage destruction, and treatment of NAC reversed the protective effect of SSZ.

Application of pulsed electromagnetic fields after microfractures to the knee: a mid-term study.

PURPOSE: Pulsed electromagnetic fields (PEMFs) may improve clinical outcomes following microfractures and prevent their decline over time. METHODS: Sixty-eight patients who underwent partial medial meniscectomy and microfractures to the medial femoral condyle for management of grade III-IV cartilage lesions were randomly divided into two groups using a block randomization procedure. After surgery, 34 patients underwent PEMFs application in the I-ONE group; 34 patients underwent placebo treatment in the placebo group. All patients had the same postoperative rehabilitation protocol. Sixty patients (28 in the I-ONE group, 32 in the placebo group) were assessed at an intermediate follow-up of two years and a minimum follow-up of five years after surgery. RESULTS: The two groups were homogeneous. There was a significant improvement from baseline to the last minimum follow up of two years. At two years, IKDC and Lysholm and Constant scores were significantly improved compared to baseline in both groups with no significant inter-group differences. At the last follow up (minimum five years), clinical and functional outcomes were decreased in both the groups, with significant better outcomes in the I-ONE group. At five years, the percentage of patients still active at the same level they were pre-operatively was greater in the I-ONE group (82% vs 68%, P = 0.28). At radiographic assessment, at the latest evaluation, six patients (21.4%) in the I-ONE group and nine (28.1%) in the placebo group demonstrated grade I-II degenerative changes according to Fairbank grading system (Χ = 0.36, P = 0.55). CONCLUSIONS: PEMFs application can improve the effectiveness of microfracture in the long term.

Special tests for assessing meniscal tears within the knee: a systematic review and meta-analysis.

BACKGROUND: Musculoskeletal knee pain is a large and costly problem, and meniscal tears make up a large proportion of diagnoses. 'Special tests' to diagnose torn menisci are often used in the physical examination of the knee joint. A large number of publications within the literature have investigated the diagnostic accuracy of these tests, yet despite the wealth of research their diagnostic accuracy remains unclear.Aim To synthesise the most current literature on the diagnostic accuracy of special tests for meniscal tears of the knee in adults. METHOD: An electronic search of MEDLINE, Cumulative Index to Nursing and Allies Health Literature (CINAHL), The Allied and Complementary Medicine Database (AMED) and SPORT Discus databases was carried out from inception to December 2014. Two authors independently selected studies and independently extracted data. Methodological quality was evaluated using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS) 2 tool. RESULTS: Nine studies were included (n=1234) and three special tests were included in the meta-analysis. The methodological quality of the included studies was generally poor. McMurray's had a sensitivity of 61% (95% CI 45% to 74%) and a specificity of 84% (95% CI 69%to 92%). Joint line tenderness had a sensitivity of 83%(95% CI 73% to 90%) and a specificity of 83% (95% CI 61% to 94%). Thessaly 20° had a sensitivity of 75%(95% CI 53% to 89%) and a specificity of 87% (95% CI 65% to 96%). CONCLUSIONS: The accuracy of the special tests to diagnose meniscal tears remains poor. However, these results should be used with caution, due to the poor quality and low numbers of included studies and high levels of heterogeneity.