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Purpose: The optimal management of degenerative meniscal tears remains controversial. Extracorporeal shockwave therapy (ESWT) has been shown to promote tissue repair in both preclinical and clinical studies; however, its effect on degenerative meniscal tears remains unknown. This study aimed to examine whether ESWT improves meniscal degeneration., Methods: This randomized trial was conducted between 2020 and 2022 and involved patients with degenerative medial meniscal tears. Patients were allocated to receive either focused ESWT (0.25 mJ/mm 2 , 2000 impulses, 3 sessions with a 1-week interval) or sham treatment. Patients were evaluated using magnetic resonance imaging (MRI) before treatment and at 12 months after treatment. The primary endpoint was improvement in meniscal degeneration, as assessed by the change in T2 relaxation time from baseline on MRI T2 mapping. Knee pain and clinical outcomes were also examined at the same time., Results: Of 29 randomized patients, 27 patients (mean age 63.9 ± 8.7 years; females 37%; ESWT group 14 patients; control group 13 patients) were included in the final analysis. At 12 months postintervention, patients in the ESWT group showed a greater decrease in the T2 relaxation time (ESWT group -2.9 ± 1.7 ms vs. control group 1.0 ± 1.9 ms; p < 0.001) and had less knee pain (p = 0.04). The clinical outcomes at 12 months post-treatment were not statistically significant. No adverse events were reported., Conclusion: ESWT decreased the T2 relaxation time in the meniscus at 12 months post-treatment. ESWT also provided pain relief, but no differences were observed in clinical outcomes., Level of Evidence: Level II., (© 2024 The Author(s). Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

There is a paucity of data regarding using platelet-rich plasma therapy for Baker's cyst-associated medial meniscal tear. To date, conservative treatments for this type of condition include aspiration of fluid effusion with steroid injection and physical therapy. When this treatment fails, arthroscopic debridement, meniscectomy, cyst decompression and open cystectomy are available surgical management options. Recurrence rates, however, are high such that even these procedures fail to provide long-term pain relief. This case study explores the benefits of leukocyte-rich platelet-rich plasma therapy in treating tears in the posterior horn of the medial meniscus with concomitant Baker's cyst. With limited studies available, this case hopes to encourage more studies to be done in the future to provide a conservative option for patients with similar cases.

Background: Arthroscopic meniscectomy is one of the most performed surgical procedures in orthopaedics. Different approaches have been proposed to improve patient recovery but with unsatisfactory results. Platelet-rich plasma (PRP) augmentation has been proposed as a strategy to improve the recovery after meniscectomy., Purpose: To investigate the clinical benefits of an intra-articular PRP injection after meniscectomy, in terms of faster and better patient recovery., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: Ninety patients were randomized into a treatment group, with arthroscopic partial meniscectomy immediately followed by a 5-mL injection of autologous conditioned plasma, and a control group with partial meniscectomy alone. Patients were evaluated at baseline and at 15, 30, 60, and 180 days of follow-up with the visual analog scale (VAS) score for pain (primary outcome), as well as with International Knee Documentation Committee subjective score, Knee injury and Osteoarthritis Outcome Score subscales, Tegner score, and EuroQol-Visual Analog Scale score. Objective evaluation was performed analyzing knee range of motion and circumference and the International Knee Documentation Committee objective score. Complications, patient judgment, and satisfaction were documented as well., Results: No major complications and an overall significant improvement in the clinical scores were observed in both groups. Overall, the comparative analysis did not demonstrate significant between-group differences in absolute values or improvements of both subjective and objective scores, as well as activity level. The improvement in terms of VAS pain score for the treatment group was significant already at 15 days (from 4.3 ± 2.5 to 2.5 ± 2.5; P = .014), while in the control group it became significant at 30 days (from 3.7 ± 2.3 to 2.0 ± 2.4; P = .004). No significant differences were observed between the 2 groups in terms of judgment of treatment results and satisfaction., Conclusion: A single postoperative injection of PRP was not able to significantly improve patient recovery after arthroscopic partial meniscectomy. PRP augmentation did not provide overall benefits at a short-term follow-up (6 months) in terms of pain relief, function, objective parameters, and return-to-sport activities., Registration: NCT02872753 (ClinicalTrials.gov identifier)., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Arthrex provided kits for this study. S.Z. has received institutional support from Fidia Farmaceutici, Cartiheal, IGEA Clinical Biophysics, Biomet, and Kensey Nash; grant support from I+; and royalties from Springer outside the submitted work. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: Knee joint osteoarthritis (OA)-related meniscal tears are still sometimes treated in centers by arthroscopic partial meniscectomy (APM), which is then followed by a solitary physical therapy regimen., Objective: The present study was conducted to compare the efficacy of intra-articular injection of ozonized platelet-rich plasma (PRP) and hyaluronic acid following arthroscopic suturing, and APM to treat meniscal tear degenerative type., Methods: In a randomized trial of prospective comparative research, 104 patients, all of whom had meniscal tears due to OA of the knee, were randomly divided into two groups. The participants in Group A (55 patients) were given intra-articular ozonized PRP and hyaluronate therapeutics, following arthroscopic suturing of meniscal tear treatment (ASMT) of degenerative knee joint OA. Group B (49 patients) was prepared for APM alone. Both groups were followed by physical therapy and a follow up visit throughout 12, 24, and 36 months. The WOMAC and Lequesne scores were evaluated., Results: At every follow up visit for 6, 12, and 24, months, there was a significant decline in the mean of WOMAC and Lequesne scores in Groups A and B relative to baseline. Additionally, Group A significantly (P<0.0001) outperformed Group B at 12, 24, and 36 months for both Lequesne's and WOMAC scores. There were infection, stiffness, and widespread OA knee degeneration detected in Group B while no serious adverse effects were observed in Group A., Conclusion: The study's findings demonstrated that physical and intra-articular orthobiological ozonized PRP and hyaluronate therapies were more effective than APM in treating degenerative knee joint OA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The quality control (QC) of pharmaceutical-grade cell-therapy products, such as mesenchymal stem cells (MSCs), is challenging. Attempts to develop such products have been hampered by difficulties defining cell-type-specific characteristics and therapeutic mechanisms of action (MoAs). Although we have developed a cell therapy product, FF-31501, consisting of human synovial MSCs (SyMSCs), it was difficult to find specific markers for SyMSCs and to define the cells separately from other MSCs. The purpose of this study was to create a method for identifying and defining SyMSCs from other tissue-derived MSCs and to delve deeper into the mechanism of action of SyMSC-induced meniscus regeneration. Specifically, as a cell-type-dependent approach, we constructed a set of 1143 genes (Amp1200) reported to be associated with MSCs and established a method to evaluate them by correlating gene expression patterns. As a result, it was possible to define SyMSCs separately from other tissue-derived MSCs and non-MSCs. In addition, the gene expression analysis also highlighted TNSF-15. The in vivo rat model of meniscus injury found TNSF-15 to be an essential molecule for meniscus regeneration via SyMSC administration. This molecule and previously reported MoA molecules allowed an MoA-dependent approach to define the mechanism of action for SyMSCs. Therefore, SyMSCs for meniscus regeneration were defined by means of two approaches: the method to separate them from other MSCs and the identification of the MoA molecules. These approaches would be useful for the QC of cell therapy products.

Objective: Ultimate frisbee can lead to severe sports injuries, especially joint injuries in the lower limbs, such as knee meniscus injuries. This study examines the impact of personalized exercise therapy on knee meniscus injuries in ultimate frisbee players in the Lingnan region of China., Methods: Seventy-six patients with confirmed meniscal injuries participated in the study, divided into an intervention group ( n  = 38) and a control group ( n  = 38). The control group received standard treatment, including drug therapy and physical therapy. The intervention group received standard treatment plus a personalized exercise regimen based on FITT-VP (frequency, intensity, time, type, volume, and progression) principles, incorporating strength training, aerobic exercise, flexibility training, neuromuscular training, and aquatic exercise. This program was monitored and adjusted over a six-month period through both online and offline methods. The primary outcomes were joint range of motion (ROM), thigh circumference atrophy index (TCAI), Lysholm Rating Scale (LRS) scores, and visual analog scores (VAS). The secondary outcome was the International Knee Documentation Committee (IKDC) score. Data were collected before the intervention, and at 1 month and 6 months after the intervention. Statistical analysis was conducted using SPSS 24.0 and GraphPad 10.0, with a significance level set at α  = 0.05., Results: After 1 month, the intervention group showed significantly better results in ROM (116.67 ± 9.063), LRS score (86.316 ± 3.750), and IKDC score (80.473 ± 5.421) compared to the control group (111.784 ± 4.778, 82.579 ± 3.818, and 77.684 ± 4.430, respectively) ( p  < 0.05). The TCAI (3.219 ± 1.889) and VAS score (1.921 ± 0.673) in the intervention group were significantly lower than those in the control group (5.228 ± 2.131 and 2.710 ± 1.112, respectively) ( p  < 0.01). After 6 months, the differences in LRS and VAS scores between the groups were not significant. However, the intervention group continued to show significant improvements in ROM (134.934 ± 3.011), TCAI (1.107 ± 1.158), and IKDC score (93.315 ± 1.847) compared to the control group (125.395 ± 18.554, 4.574 ± 1.109, and 87.789 ± 4.437, respectively) ( p  < 0.05)., Conclusion: Personalized exercise prescriptions offer significant therapeutic and rehabilitative benefits for ultimate frisbee players with knee meniscus injuries. This approach helps to reduce symptoms, alleviate pain, and improve joint function, muscle strength, and athletic performance after sports-related injuries., 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 © 2024 Chen, Du, Gao, Li, Zheng, Xie and Zhong.)

Soccer is considered the most popular sport in the world. The game involves frequent agile maneuvers, such as rapid accelerations/decelerations and pivoting, and carries an inherent risk of high-speed collisions, which can lead to lower extremity injury. Knee and meniscus injuries can cause significant pain and disability, precluding participation in the sport. Understanding the diagnosis and management of meniscal injuries in soccer players is essential to the care of these athletes. This paper reviews meniscal anatomy, biomechanics, and mechanisms of injury; discusses the work-up, diagnosis, and management of meniscus injuries; and reports on rehabilitation, return to sport, and outcomes after meniscal injuries in soccer players., Competing Interests: Disclosure: R.H.B. is the chief medical officer for St. Louis City SC of Major League Soccer (MLS). The remaining author declares no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The self-repair ability after meniscal tears is poor, leading to the development of posttraumatic osteoarthritis. Promoting the repair of meniscal injuries remains a great challenge, especially in the avascular region., Hypothesis: Local delivery of skeletal stem cell (SSC)-derived exosomes (SSC-Exos) would promote meniscal healing and prevent secondary osteoarthritis progression., Study Design: Controlled laboratory study., Methods: SSCs were isolated from bone marrow and exosomes were extracted via ultracentrifugation. The cell migration capabilities after incubation with exosomes were validated through in vitro cell culture. Full-thickness longitudinal medial meniscal tears were performed in the avascular region of 40 male Sprague-Dawley rats and 20 male New Zealand White rabbits, which were randomly divided into 2 groups: group treated with phosphate-buffered saline (G CON ) and group treated with exosomes (G Exosome ). The effects of these treatments on meniscal healing and secondary osteoarthritis were evaluated by gross inspection, biomechanical testing, and histological assessment. RNA sequencing of in vitro cell cultures was performed to explore the underlying mechanisms., Results: Exosomes were successfully extracted and identified. These exosomes significantly promoted cell migration capabilities in vitro ( P < .01). The G Exosome exhibited greater cell proliferation and tissue regeneration with type 2 collagen secretion, and a significantly higher meniscal repair score than that of the G CON at 8 weeks postoperatively ( P < .05). In contrast to the degenerative changes in both the meniscus and articular cartilage of the G CON , meniscal tissue in the G Exosome exhibited restoration of normal morphology with a smooth and glossy white surface and better mechanical strength at 8 weeks after meniscal repair. Both degeneration scores and synovitis scores were significantly higher in the G CON than in the G Exosome ( P < .05). Compared with the G CON , the expression of key genes related to cell migration, such as the chemokine family, was enhanced by exosome injection, leading to an upregulation of extracellular matrix expression while downregulating the expression of inflammation-related genes such as CD68 and the matrix metalloproteinase family., Conclusion: The administration of SSC-Exos effectively promoted meniscal healing in the avascular region and ameliorated secondary osteoarthritis. The effect might be attributed to inflammation modulation, promotion of cell migration, and secretion of extracellular matrix components., Clinical Relevance: Injection of SSC-Exos represents a promising therapeutic option for promoting meniscal healing in the avascular region., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by National Natural Science Foundation of China (No. 82072428, No. 823B2057) and Natural Science Foundation of Beijing, China (No. 7212132). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: Meniscal repair should be the gold standard. However, the meniscus is poorly vascularized and even an excellent meniscus repair may not heal. Therefore, numerous studies and systematic reviews have been carried out on platelet-rich plasma (PRP), mesenchymal stem cells (MSCs) and fibrin clots for meniscal augmentation, but the results remain controversial. This systematic review aimed to identify other emerging strategies for meniscal repair augmentation and to assess whether there are different avenues to explore in this field., Methods: A systematic literature review was conducted in August 2022. PubMed, Ovid MEDLINE(R) all, Ovid All EBM Reviews, Ovid Embase and ISI Web of Science databases were searched. In Vivo animal and human studies concerning the biological augmentation of meniscal lesions by factors other than PRP, MSCs or fibrin clots were included. Cartilage-only studies, previous systematic reviews and expert opinions were excluded. All data were analyzed by two independent reviewers., Results: Of 8965 studies only nineteen studies covering 12 different factors met the inclusion criteria. Eight studies investigated the use of growth factors for meniscal biologic augmentation, such as vascular endothelial growth factor or bone morphogenic protein 7. Five studies reported on cell therapy and six studies focused on other factors such as hyaluronic acid, simvastatin or atelocollagen. Most studies (n = 18) were performed on animal models with gross observation and histological evaluation as outcomes. Polymerase chain reaction and immunohistochemistry were also common. Biomechanical testing was the object of only two studies., Conclusions: Although several augmentation strategies have been attempted, none has yielded conclusive results, testifying to a lack of understanding with regard to meniscal healing. More research is needed to better understand the pathways that regulate meniscus repair and how to act positively on them., Level of Evidence: Systematic review of case-control and animal laboratory studies., (© 2024. The Author(s).)

Introduction: Pain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective., Methods and Analysis: The Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement., Ethics and Dissemination: The trial was approved by the London-Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist., Trial Registration Number: ISRCTN87336549., Competing Interests: Competing interests: AM, MU and HP are co-investigators on two current (RACER-Knee and RACER-Hip) and one completed (START:REACTS) NIHR funded studies (AM chief investigator of two) that have, or have had, additional support from Stryker Ltd. There is no link to the current trial. AM, MU and HP are co-investigators on grants funded by the Australian NHMRC. MU is chief investigator or co-investigator on multiple previous and current research grants from the UK National Institute for Health Research, and is a co-investigator on grants funded by the Norwegian MRC. He was an NIHR Senior Investigator until March 2021. He is a director and shareholder of Clinvivo Ltd that provides electronic data collection for health services research. He is part of an academic partnership with Serco Ltd, funded by the European Social Fund, related to return-to-work initiatives., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Degenerative meniscal tear (DMT) is common in the elderly population. However, there has been controversy over the treatment of DMT regarding whether to adopt arthroscopic partial meniscectomy (APM) or exercise therapy (ET). In order to compare the long-term outcomes between the two treatment methods, we conducted a meta-analysis of randomized controlled trials (RCTs) with long-term follow-up., Methods: PubMed, Cochrane Library, Embase, and Web of Science were last searched on 16 April 2023 for studies on DMT that compared the clinical outcomes between APM and ET. The subjective outcomes of the comparison include the Knee Injury and Osteoarthritis Outcome Score (KOOS), which consists of five sub-scales: pain, symptoms, activities of daily living (ADL), sport and recreation (Sport/recreation), and quality of life (QOL). The objective outcome includes knee osteoarthritis progression., Results: We identified 6 potentially eligible trials, including 1078 participants, from the literature search. ET showed a lower risk of knee osteoarthritis progression than APM (RR, 1·27; 95%CI 1·05 to 1·53). There were no statistically significant differences in the KOOS-pain, KOOS-symptoms, KOOS-ADL, KOOS-Sport/recreation, and KOOS-QOL between the two treatment methods., Conclusion: For the treatment of DMT, ET showed a lower risk of knee osteoarthritis progression than APM. ET and APM had comparable effects on subjective outcomes including pain management and knee function. Therefore, it is not recommended to use APM but rather recommended to use ET for treating APM., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

OBJECTIVE: To compare the effect of early meniscal surgery versus exercise and education with the option of later surgery on pain, function, and quality of life in young patients with a meniscal tear, taking symptom onset into account. DESIGN: Randomized controlled trial. METHODS: In a randomized controlled trial (the "Danish RCT on Exercise versus Arthroscopic Meniscal surgery for young adults" [DREAM] trial), 121 patients aged 18-40 years with a magnetic resonance imaging-verified meniscal tear were randomized to surgery or 12 weeks of supervised exercise and patient education. For this exploratory study, the analyses were stratified by symptom onset (traumatic/nontraumatic). The main outcome was the difference in change after 12 months in the mean score of 4 Knee injury and Osteoarthritis Outcome Score subscales (KOOS 4 ) covering pain, symptoms, function in sport and recreation, and quality of life. RESULTS: Forty-two patients (69%) in the exercise therapy group and 47 (78%) in the surgery group were categorized as having a traumatic tear. We observed no difference in change in the KOOS 4 after 12 months between the 2 treatment groups for either traumatic tears (18.8 versus 16.0 in the surgery versus exercise therapy groups; adjusted mean difference, 4.8 [95% confidence interval, -1.7 to 11.2]) or nontraumatic tears (20.6 versus 17.3 in the surgery versus exercise therapy groups; adjusted mean difference, 7.0 [95% confidence interval, -3.7 to 17.7]). CONCLUSION: In patients with traumatic and nontraumatic meniscus tears, early meniscal surgery did not appear superior to exercise and education in improving pain, function, and quality of life after 12 months. Further research is needed to confirm the clinical applicability of these findings. J Orthop Sports Phys Ther 2024;54(5):1-10. Epub 22 February 2024. doi:10.2519/jospt.2024.12245 .

Objective: This study aimed to synthesize the evidence from randomized clinical trials in people with nontraumatic degenerative meniscal pathology by comparing physical therapist interventions versus or combined with arthroscopic partial meniscectomy (APM)., Methods: Seven electronic databases were searched. Methodological quality was evaluated using the Physiotherapy Evidence Database scale. Data synthesis was performed with random-effects network meta-analysis, and results were summarized using the standardized mean differences., Results: From 2103 studies, 10 randomized clinical trials comprising 1411 individuals were included. Ninety percent of the selected randomized clinical trials were classified as good quality according to the Physiotherapy Evidence Database scale. All interventions (physical therapist interventions, APM, and APM plus physical therapist interventions) showed reduced pain and physical impairments at 3-month follow-up. However, when a physical therapist intervention was included, greater reductions in pain at rest (APM vs physical therapist interventions: 0.73 [95% CI = 0.20 to 1.26]; APM vs APM plus physical therapist interventions: 0.59 [95% CI = 0.15 to 1.03]) and greater increases in the strength of knee extensor muscles (APM vs physical therapist interventions: 0.44 [95% CI = 0.07 to 0.80]; APM vs APM plus physical therapist interventions: 0.73 [95% CI = 0.29 to 1.16]) were observed at 3 months. By contrast, no differences were found between treatments beyond 3 months., Conclusion: Physical therapist interventions based on exercise programs demonstrate superior short-term outcomes in pain reduction and knee extensor strength compared to surgical treatment., Impact: For nontraumatic degenerative meniscal pathology, conservative treatment utilizing a physical therapist intervention approach should be prioritized as the first choice over surgical treatment. It offers comparable or superior short-term pain reduction and strength improvements, with a lower risk of side effects. In cases where surgery is deemed necessary, including postsurgical, physical therapist interventions are highly recommended to enhance muscle strength and alleviate pain., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The reliable data on the incidence of hypermobile lateral meniscus (HLM) and its clinical manifestations, diagnostic methods and therapeutic approaches are limited. This systematic study aimed to review available treatment options for HLM and the outcomes of each approach., Methods: A systematic search was performed in four electronic databases (PubMed, EMBASE, Scopus, Web of Science) to identify studies in which arthroscopically confirmed cases of HLM were treated surgically or nonsurgically, and the required data comprising study characteristics, patient data, treatment approaches and outcome measures were extracted from eligible studies., Results: Twenty studies with a total of 212 patients (138 males and 74 females) and 219 knees were included. The most frequently reported symptoms were locking sensations, knee pain, giving way and snapping. Treatments used by the studies were: radiofrequency energy in two studies; arthroscopic partial meniscectomy in one study; open surgery in two studies; and arthroscopic meniscal repair in 17 studies. Eleven studies used an all-inside repair method and an inside-out meniscal repair was reported in eight studies. Three studies reported the usage of posterior arthroscopy for therapeutic or diagnostic approaches. Evaluation of symptom resolution was the main outcome measurement for which almost all of the studies stated relief of symptoms after intervention., Conclusion: Despite the lack of definite consensus about the most appropriate intervention for HLM, therapeutic preference was directed towards arthroscopic all-inside and inside-out repair techniques. Although the surgeon's decision remains the key factor in choosing the most suitable treatment option for each individual, posterior arthroscopic meniscal repair may be considered as a better option for HLM treatment according to the findings of this review., Level of Evidence: Level IV., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Importance: Approximately 5% of all primary care visits in adults are related to knee pain. Osteoarthritis (OA), patellofemoral pain, and meniscal tears are among the most common causes of knee pain., Observations: Knee OA, affecting an estimated 654 million people worldwide, is the most likely diagnosis of knee pain in patients aged 45 years or older who present with activity-related knee joint pain with no or less than 30 minutes of morning stiffness (95% sensitivity; 69% specificity). Patellofemoral pain typically affects people younger than 40 years who are physically active and has a lifetime prevalence of approximately 25%. The presence of anterior knee pain during a squat is approximately 91% sensitive and 50% specific for patellofemoral pain. Meniscal tears affect an estimated 12% of the adult population and can occur following acute trauma (eg, twisting injury) in people younger than 40 years. Alternatively, a meniscal tear may be a degenerative condition present in patients with knee OA who are aged 40 years or older. The McMurray test, consisting of concurrent knee rotation (internal or external to test lateral or medial meniscus, respectively) and extension (61% sensitivity; 84% specificity), and joint line tenderness (83% sensitivity; 83% specificity) assist diagnosis of meniscal tears. Radiographic imaging of all patients with possible knee OA is not recommended. First-line management of OA comprises exercise therapy, weight loss (if overweight), education, and self-management programs to empower patients to better manage their condition. Surgical referral for knee joint replacement can be considered for patients with end-stage OA (ie, no or minimal joint space with inability to cope with pain) after using all appropriate conservative options. For patellofemoral pain, hip and knee strengthening exercises in combination with foot orthoses or patellar taping are recommended, with no indication for surgery. Conservative management (exercise therapy for 4-6 weeks) is also appropriate for most meniscal tears. For severe traumatic (eg, bucket-handle) tears, consisting of displaced meniscal tissue, surgery is likely required. For degenerative meniscal tears, exercise therapy is first-line treatment; surgery is not indicated even in the presence of mechanical symptoms (eg, locking, catching)., Conclusions and Relevance: Knee OA, patellofemoral pain, and meniscal tears are common causes of knee pain, can be diagnosed clinically, and can be associated with significant disability. First-line treatment for each condition consists of conservative management, with a focus on exercise, education, and self-management.

Menisci play an important role in the biomechanics of knee joint function, including loading transmission, joint lubrication, prevention of soft tissue impingement during motion and joint stability. Meniscal repair presents a challenge due to a lack of vascularization that limits the healing capacity of meniscal tissue. In this review, the authors aimed to untangle the available treatment options for repairing meniscal tears. Various surgical procedures have been developed to treat meniscal tears; however, clinical outcomes are limited. Consequently, numerous researchers have focused on different treatments such as the application of exogenous and/or autologous growth factors, scaffolds including tissue-derived matrix, cell-based therapy and miRNA-210. The authors present current and prospective treatment strategies for meniscal lesions.

Abstract: Meniscus root tears are important to recognize early given their potentially devastating consequences on joint health. This injury results in the lost ability of the meniscus to transfer axial loads into hoop stress; therefore, it is functionally equivalent to a complete meniscectomy. This causes rapid progression of osteoarthritis and increased need to total knee arthroplasty in a previously healthy joint. Despite these consequences, root tears have only been discussed in the orthopedic literature in the last 10 to 15 years and have not been routinely integrated into nonoperative sports medicine education. It is important for all nonoperative sports medicine providers to properly diagnose and triage this injury early in its course to maximize joint preservation efforts. The goal of this manuscript is to review the anatomy, presentation, natural history, imaging, and treatment options for meniscal root tears., (Copyright © 2022 by the American College of Sports Medicine.)

BACKGROUND: Surgery is commonly used to treat meniscal tears; however, to our knowledge, no randomized controlled trials (RCTs) have compared surgery with nonsurgical alternatives in young adults. We hypothesized that early meniscal surgery would be superior to a strategy of exercise and education with the option of surgery later if needed. METHODS: In this pragmatic parallel-group RCT, we enrolled young adults (18-40 years of age) with magnetic resonance imaging–verified meniscal tears eligible for surgery from seven Danish hospitals. Patients were randomly assigned (1:1) to surgery (partial meniscectomy or meniscal repair) or 12-week supervised exercise therapy and education with the option of surgery later if needed. The primary outcome was the difference in change from baseline to 12 months in the mean score of four Knee Injury and Osteoarthritis Outcome Score (KOOS4) subscales covering pain, symptoms, function in sport and recreation, and quality of life, ranging from 0 (worst) to 100 (best). RESULTS: We enrolled 121 young adults (mean age, 29.7 years; 28% were female). In total, 107 participants (88%) completed the 12-month follow-up; 16 participants (26%) from the exercise group crossed over to surgery, while 8 (13%) from the surgery group did not undergo surgery. Intention-to-treat analysis showed no statistically significant difference in change between groups from baseline to 12 months in KOOS4 scores (19.2 vs. 16.4 in the surgery vs. exercise groups; adjusted mean difference, 5.4 [95% confidence interval, −0.7 to 11.4]). No difference in serious adverse events was observed (four vs. seven in the surgery and exercise groups, respectively; P=0.40). Per-protocol and as-treated analyses yielded similar results. CONCLUSIONS: Our results suggest that among young, active adults with meniscal tears, a strategy of early meniscal surgery is not superior to a strategy of exercise and education with the option of later surgery. Both groups experienced clinically relevant improvements in pain, function, and quality of life at 12 months, and one of four from the exercise group eventually had surgery. (Funded by the Danish Council for Independent Research, IMK Almene Fond, Lundbeck Foundation, Spar Nord Foundation, Danish Rheumatism Association, Association of Danish Physiotherapists Research Fund, Research Council at Næstved-Slagelse-Ringsted Hospitals, and Region Zealand; ClinicalTrials.gov number, NCT02995551.)

Background: Meniscus tears are usually classified as degenerative or traumatic tears according to their pathogenesis. At present, traumatic meniscal tears are generally believed to have high healing potential. In recent years, multiple treatments have been described for traumatic meniscal tears, such as the inside-out technique, outside-in technique, all-inside technique, biological augmentation of meniscal repair, meniscectomy, and non-surgical treatment. However, the functional recovery of the knee joint and healing of the meniscus after treatment are quite different from the results reported in the literature, which requires more reliable evidence-based medical findings. This study will evaluate evidence from multiple types of research comparing different therapies for traumatic meniscal tears in adults., Methods: We will search the EMBASE, Cochrane Library (the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials [CENTRAL], Cochrane Methodology Register), PubMed, Web of Science (Science and Social Science Citation Index), China Knowledge Network, CBM, Wanfang data, and VIP electronic databases from their inception to August 10, 2021, with no language restrictions. We will also manually search Baidu and Google Scholar to identify randomized controlled studies, non-randomized controlled studies, and cohort studies on the treatment of traumatic meniscal tears. Two researchers will independently screen the literature, extract the data, and evaluate the quality of the studies. Software programs, including Microsoft Access, Excel, Stata (Version 15), WinBUGS (Version 1.4.3), and ADDIS (Version 1.16.8), were used to analyze and manipulate the data., Results: In this study, the main outcomes were physical function and healing rate, based on the Western Ontario and McMaster Universities Osteoarthritis Index, Lysholm Knee Scoring Scale, Knee Injury and Osteoarthritis Outcome Score, Functional Recovery Scale, and clinical healing rate. The secondary indexes included total cost, cost-effectiveness ratio, incremental cost-effectiveness ratio, Tegner activity scale score, visual analogue scale, numerical rating scale, and meniscal tear complications., Conclusions: This systematic review will provide reliable evidence-based findings for the clinical application of different therapies for traumatic meniscal tears in adults., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

This review summarizes the literature of preclinical studies and clinical trials on the use of mesenchymal stem cells (MSCs) to treat meniscus injury and promote its repair and regeneration and provide guidance for future clinical research. Due to the special anatomical features of the meniscus, conservative or surgical treatment can hardly achieve complete physiological and histological repair. As a new method, stem cells promote meniscus regeneration in preclinical research and human preliminary research. We expect that, in the near future, in vivo injection of stem cells to promote meniscus repair can be used as a new treatment model in clinical treatment. The treatment of animal meniscus injury, and the clinical trial of human meniscus injury has begun preliminary exploration. As for the animal experiments, most models of meniscus injury are too simple, which can hardly simulate the complexity of actual meniscal tears, and since the follow-up often lasts for only 4-12 weeks, long-term results could not be observed. Lastly, animal models failed to simulate the actual stress environment faced by the meniscus, so it needs to be further studied if regenerated meniscus has similar anti-stress or anti-twist features. Despite these limitations, repair of the meniscus by MSCs has great potential in clinics. MSCs can differentiate into fibrous chondrocytes, which can possibly repair the meniscus and provide a new strategy for repairing meniscus injury., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Purpose . To determine the 5-year success rate of the "all-inside" technique of arthroscopic meniscus suture and collagen membrane wrapping along with bone marrow blood injection, to evaluate the progression of degenerative changes and the impact of simultaneous anteriro cruciate ligament (ACL) reconstruction. Methods . Fifty-four consecutive patients with complex meniscal tears were treated with the previously described technique. The subjective scores (International Knee Documentation Committee 2000, Lysholm, EQ-5D-5L) and Barret clinical criteria of meniscal healing were recorded. Magnetic resonance images (MRIs) were assessed at 2 and 5 years postoperatively, using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) criteria. Kaplan-Meier survival analyses were performed in order to assess the survivorship after the index procedure. Thirty-nine patients were divided into 2 groups: group A-isolated meniscus repair and group B-meniscus repair with concurrent ACL reconstruction. Results . Fifty-four patients were treated and 44 were available for analysis. There was a statistically significant improvement in subjective scores and clinical assessment between the preoperative, 2-year follow-up, and 5-year follow-up time points. EQ-5D-5L utility value was 0.9 ± 1 at final follow-up. The WORMS osteoarthritis severity grade had increased from 6.9 ± 5.0 points at the 2-year follow-up to 11.1 ± 9.6 points at the 5-year follow-up ( P < 0.001). There was a significant difference between the groups after 60 months. The overall survival rate at final follow-up was 88%. Conclusions . The treatment option evaluated in this study has shown very good mid-term clinical and MRI-based outcomes as well as a favorable survival rate. Simultaneous ACL reconstruction is likely a factor for osteoarthritis progression.

Objective: To investigate meniscal regeneration and prevent cartilage degeneration using wrapping treatment for meniscal horizontal tears that have been difficult to repair in rabbits., Design: Thirty knees from 15 Japanese white rabbits were divided into the horizontal (horizontal tears) or wrapping (horizontal tears with wrapping treatment) groups. Horizontal tears were created and wrapped with a sheet scaffold containing polyglycolic acid, polylactic acid, and polycaprolactone. The meniscus was stained with Safranin-O/Fast Green and evaluated with modified Pauli scores at 8, 12, and 16 weeks after implantation ( n = 5). Cell morphology was determined with hematoxylin and eosin staining. Mature collagen was confirmed with Picrosirius Red staining. Furthermore, immunohistochemical analysis of inducible nitric oxide synthase (iNOS) for inflammation, Ki-67 for proliferation, and type II collagen for regeneration was performed. Medial femoral cartilage was stained with Safranin-O/Fast Green and evaluated with the Osteoarthritis Research Society International score at 8 and 16 weeks., Results: The wrapping group had significantly better regeneration than the horizontal group, especially at 16 weeks ( P < 0.05). Wrapping treatment induced fibrochondrocyte-like cells at 16 weeks. After wrapping treatment, iNOS was overexpressed at 8 weeks, Ki-67 at 8 and 12 weeks, and type II collagen at 16 weeks. Cartilage degeneration in the wrapping group did not progress significantly compared with that in the horizontal group at 16 weeks ( P < 0.05)., Conclusions: Wrapping treatment for meniscal horizontal tears induced meniscal regeneration as the sheet scaffold might induce intrinsic and extrinsic repair. Regaining the meniscal function by the wrapping treatment prevented cartilage degeneration.

Meniscal degeneration is a common finding even in young patients' knees, and it is regarded as a predictor for the onset of early osteoarthritis (OA). When symptomatic, it represents a challenge since arthroscopic surgery provides unpredictable results: recent evidence has shown that partial meniscectomy is not better than conservative management up to 2 years of follow-up, and the removal of meniscal tissue may accelerate OA progression toward OA. Intra-articular injection of corticosteroids or hyaluronic acid may help in providing temporary symptomatic relief, but no influence should be expected on the quality of the meniscal tissue. Biologic agents have been adopted to treat a variety of degenerative musculoskeletal pathologies, and the use of platelet-derived growth factors (GFs) has become routine. Preclinical studies have documented that platelet-derived GFs may play a beneficial role in stimulating meniscal repair and regeneration by triggering anabolic pathways and stimulating local mesenchymal stem cells from synovium. Furthermore, also mechanical stimulation (e.g., arthroscopic trephination or percutaneous needling) in the red-red or red-white zone may further promote tissue healing. The purpose of the present brief report is to describe the clinical outcomes at 18 months' follow-up in a cohort of patients affected by symptomatic medial meniscus degeneration and treated by percutaneous needling plus intra- and perimeniscal injection of autologous conditioned plasma (ACP). The procedure was shown to be safe and provided significant pain reduction and improvement in subjective scores. This treatment option deserves further investigation in a comparative setting, to establish whether it could offer advantage over isolated intra-articular injections.

Objective: To investigate the role of autologous platelet-rich plasma (PRP) on the repair of meniscal white-white zone injury through promoting the proliferation of canine bone marrow-derived mesenchymal stem cells (BMSCs)., Methods: A total of 24 beagle dogs were selected to construct meniscal white-white zone injury models in both lateral knee joints. All subjects were divided into four groups: control, BMSCs, PRP, and PRP + BMSCs. Immunohistochemistry was applied in the expression detection of type I and type II collagens. HE staining and methylene blue staining were performed to observe the injury of cartilage of lateral femoral condyle in each group. ELISA was used to detect the osteopontin (OPN) content in cartilage of lateral femoral condyle. HE staining and magnetic resonance imaging (MRI) were used to observe the healing of meniscus in each group. Outcome measures include the expression of OPN in the synovial fluid of knee joint, the expression of type I collagen and type II collagen, the healing of meniscus injury, and the damage degree of lateral femoral condyle cartilage., Results: Compared with the control group, the expressions of type I and type II collagens were enhanced in the PRP group and the PRP + BMSCs group. Compared with 1 week before modeling, the expression of OPN was elevated in the control group and the BMSCs group at 3 weeks after modeling. There were no significant differences in the above indicators between the PRP group and the PRP + BMSCs group. According to MRI and pathological section after HE staining, meniscal healing in the PRP group and the PRP + BMSCs group was significantly improved as compared to that of the control group and the BMSCs group (all P < 0.05), and there was no significant difference between the PRP group and the PRP + BMSCs group (P > 0.05). All subjects were divided into the non-healing group and the healing group in accordance with the HE staining results in previous experiment. The injury of cartilage of lateral femoral condyle was significantly heavier in the non-healing group than that in the healing group., Conclusion: The application of PRP alone or in combination with BMSCs could promote the clinical healing rate of meniscal white-white zone injury., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objective: Conservative and surgical treatments for meniscal lesions are various and this field of orthopedic surgery is in continuous development. Stem cells represent one of the current options to stimulate meniscal healing. The present systematic review aimed at summarizing the state of art in the application of stem cells for the treatment of meniscal damage both at pre-clinical and clinical level., Materials and Methods: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to perform this systematic review. A systematic search was performed using the PubMed (MEDLINE), EMBASE and Cochrane Library databases. All the studies dealing with the application of stem cells as a treatment for meniscal tears were pooled, data were extracted and analyzed. The studies were divided into two groups (pre-clinical and clinical), and then, discussed independently., Results: A total of 18 studies were included. Thirteen were classified as "pre-clinical" and five as "clinical". The most commonly used cells were mesenchymal stem cells (MSC), derived from bone marrow (BMMSC), synovial tissue (SMSC), or adipose tissue (ADSC). Follow-ups ranged from 2 to 16 weeks for the pre-clinical studies and from 3 to 24 months for the clinical studies. All studies documented good results in terms of laboratory markers/scores, clinical and radiologic evaluation., Conclusions: Based on the currently available data, it is not possible to establish the best cell source or delivery method for the treatment of meniscal injuries. Bone Marrow derived stem cells delivered through injection represent the most studied approach, with the most promising results. However, the full impact of these therapies through their different sub-type of stem cells and implantation techniques still needs to be critically analyzed through larger randomized controlled trials with longer follow-up.

Background: Complex meniscal lesions often require meniscectomy with favorable results in the short term but a high risk of early osteoarthritis subsequently. Partial meniscectomy treated with meniscal substitutes may delay articular cartilage degeneration., Purpose: To evaluate the status of articular cartilage by T2 mapping after meniscal substitution with polyurethane scaffolds enriched with mesenchymal stem cells (MSC) and comparison with acellular scaffolds at 12 months., Methods: Seventeen patients (18-50 years) with past meniscectomies were enrolled in 2 groups: (1) acellular polyurethane scaffold (APS) or (2) polyurethane scaffold enriched with MSC (MPS). Patients in the MPS group received filgrastim to stimulate MSC production, and CD90+ cells were obtained and cultured in the polyurethane scaffold. The scaffolds were implanted arthroscopically into partial meniscus defects. Concomitant injuries (articular cartilage lesions or cartilage lesions) were treated during the same procedure. Changes in the quality of articular cartilage were evaluated with T2 mapping in femur and tibia at 12 months., Results: In tibial T2 mapping, values for the MPS group increased slightly at 9 months but returned to initial values at 12 months ( P > 0.05). In the APS group, a clear decrease from 3 months to 12 months was observed ( P > 0.05). This difference tended to be significantly lower in the APS group compared with the MPS group at the final time point ( P = 0.18). In the femur, a slight increase in the MPS group (47.8 ± 3.4) compared with the APS group (45.3 ± 4.9) was observed ( P > 0.05)., Conclusion: Meniscal substitution with polyurethane scaffold maintains normal T2 mapping values in adjacent cartilage at 12 months. The addition of MSC did not show any advantage in the protection of articular cartilage over acellular scaffolds ( P > 0.05).

Background: Meniscal tears are commonly observed in patients with knee osteoarthritis (OA), however, clinical significance of such lesions detected by magnetic resonance imaging is in many cases unclear. This study aimed to determine the clinical effectiveness of arthroscopic partial meniscectomy (APM) compared with non-operative care in patients with knee OA., Method: We used existing systematic reviews with updates of latest studies. Three randomized controlled studies were selected, where two studies compared the effects of APM plus physical therapy (PT) with PT alone and one compared APM alone and PT alone. While 1 study exclusively included OA patients, 2 studies included 21.1 and 12% of patients with no radiographic OA. Patients with knee locking were unanimously excluded., Results: Upon comparison of APM plus PT and PT alone, there was no significant difference observed in knee function, physical activity, or adverse events. Knee pain was observed to be significantly lower in the APM plus PT group at 6 months, but there was no difference between the two groups at 12 and 24 months. With respect to the comparison between APM alone and PT alone, PT was non-inferior based on the criteria for knee function during 24 months; however, knee pain was significantly reduced in the APM alone group., Conclusions: Our study showed that knee pain was significantly improved in the APM group compared to non-operative care group at 6 months and over 24 months. Our result was based on only 3 randomized controlled trials (RCTs) revealing a significant knowledge gap, hence demanding more high-quality RCTs in OA patients., Trial Registration: PROSPERO Identifier: CRD42020215965., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

The menisci play a vital role in maintaining knee function and protecting the chondral surfaces. Acute and chronic tears are common injuries among both young athletes and older patients with early degenerative changes. The progression of physiological derangement and chondral injury after meniscus injury and meniscectomy have prompted interest in expanding meniscus repair techniques. Recent literature encourages an attempt at repair in tear patterns previously declared irreparable if the tissue quality allows. The orthopedic surgeon should understand the multitude of techniques available to them and be prepared to combine techniques to optimize the quality of their repair construct. While biological augmentation may show some promising early results, the quality of the current data precludes strong recommendations in their favor., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Meniscus surgery is one of the most commonly performed orthopedic procedures worldwide. Modifiable risk factors for meniscus injury include body mass index, participation in athletics and occupation. Nonmodifiable risk factors include age, sex, lower extremity alignment, discoid meniscus, ligamentous laxity, and biconcave tibial plateau. Conditions commonly associated with meniscal injury are osteoarthritis, anterior cruciate ligament injury, and tibial plateau fractures. Tear type and location vary by patient age and functional status. Surgical management of meniscus injury is typically cost-effective in terms of quality-adjusted life years. The purpose of this review is to provide an overview of meniscal injury epidemiology by summarizing tear types and locations, associated conditions, and factors that increase the risk for meniscal injury. The economic burden of meniscus injury and strategies to prevent injury to the meniscus are also reviewed., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Meniscal tears may be managed through conservative physical therapy and nonsteroidal anti-inflammatory medications or operative intervention. Meniscal repair is superior to partial meniscectomy with better functional outcomes and less severe degenerative changes over time. Surgical advances in operative techniques, modern instrumentation and biological enhancements collectively improve healing rates of meniscal repair. However, failed repair is not without consequences and can negative impact patient outcomes. Therefore, it is imperative for surgeons to have a thorough understanding of the vascular zones and biomechanical classifications of meniscal tears in order to best determine the most appropriate treatment., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To identify trajectories of patient-reported knee function over 5 years in patients with degenerative meniscal tears, and to explore whether baseline characteristics were associated with trajectories of sport and recreational function., Design: Prospective cohort study., Methods: We conducted a secondary exploratory analysis of the Odense-Oslo Meniscectomy Versus Exercise randomized controlled trial. Patient-reported knee function was assessed with the Knee injury and Osteoarthritis Outcome Score (KOOS) at baseline, 3 months, 1 year, 2 years, and 5 years. We used group-based trajectory modeling to identify subgroups of patients who followed distinctive patterns of change. Multinomial logistic regression was used to examine the associations of patient demographics, knee function, and disease-related factors with KOOS sport and recreational function subscale trajectories., Results: The analysis of data from a sample of 140 participants identified 3 trajectories for all KOOS subscales: (1) low, minimal improvement (10%-12% of the participants), (2) moderate, gradual improvement (20%-36%), and (3) high, early improvement (53%-70%). Baseline prognostic factors for deteriorating function in sport and recreational activities were higher body mass index, poorer mental health, greater knee pain, lower perceived knee function, poorer quadriceps and hamstrings muscle strength, poorer functional performance, more meniscal extrusion, and radiographic signs of knee osteoarthritis., Conclusion: We found 3 distinct trajectories of patient-reported knee function over 5 years: (1) low, minimal improvement, (2) moderate, gradual improvement, and (3) high, early improvement. Nine in every 10 participants improved at least gradually over 2 years after diagnosis of a degenerative meniscal tear. J Orthop Sports Phys Ther 2021;51(6):289-297. Epub 10 May 2021. doi:10.2519/jospt.2021.10025 .

Injury to the meniscus is common and frequently leads to the development of post-traumatic osteoarthritis (PTOA). Many times meniscus injuries occur coincident with anterior cruciate ligament (ACL) injuries and lead to a bloody joint effusion. Hemarthrosis, or bleeding into the joint, has been implicated in degeneration of joint tissues. The goal of this review paper is to understand the pathophysiology of blood-induced joint damage, the possible effects of blood on meniscus tissue, and the implications for current meniscus repair techniques that involve the introduction of blood-derived products into the joint. In this review, we illustrate the similarities in the pathophysiology of joint damage due to hemophilic arthropathy (HA) and osteoarthritis (OA). Although numerous studies have revealed the harmful effects of blood on cartilage and synovium, there is currently a gap in knowledge regarding the effects of hemarthrosis on meniscus tissue homeostasis, healing, and the development of PTOA following meniscus injury. Given that many meniscus repair techniques utilize blood-derived and marrow-derived products, it is essential to understand the effects of these factors on meniscus tissue and the whole joint organ to develop improved strategies to promote meniscus tissue repair and prevent PTOA development., (Copyright © 2020 Osteoarthritis Research Society International. All rights reserved.)

Introduction: Early recognition of potential predictors on the success of conservative treatment of anterior cruciate ligament (ACL) is important, as appropriate treatment can be applied to each individual patient. The goal of this study is to assess the patient demographic and radiological parameters that predict coping with ACL injuries., Methods: All patients presenting with a complete ACL injury between 2014 and 2018 at our clinic were included. The role of patient demographics (age, gender, activity level, meniscus injury and time from injury to clinic), and ACL tear location, bone bruises, tibial slope, and anterolateral ligament (ALL) injury were assessed on the success of conservative treatment using univariate and multivariate analyses., Results: Sixty-five patients (32%) were copers and 141 (68%) were non-copers. Univariate analysis showed that copers were significantly older (40 vs. 27 years, P < 0.001), had lower preinjury activity level (Tegner 5.7 vs. 6.5, P < 0.001) and less often lateral meniscus tears (16% vs. 5%, P = 0.019) but not medial meniscus tears (17% vs. 14%, P = 0.609) than non-copers. Multivariate analysis revealed that increasing age (P < 0.001), Tegner level ≤ 6 (P = 0.003) and no meniscus injury (P = 0.045) were independent predictors of coping with ACL deficiency., Conclusions: Older age, participation in lower activity sports levels and absence of meniscus injury were predictive of coping with ACL deficiency, whereas there was no such role for tear location, tibial slope, lateral bone bruise presence, ALL injury or gender. These findings might help to identify potential copers and guide surgeons early in the optimal treatment for patients with ACL injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The inner avascular zone of the meniscus has limited healing capacity as the area is poorly vascularized. Although peptide hydrogels have been reported to regenerate bone and cartilage, their effect on meniscus regeneration remains unknown. We tested whether the self-assembling peptide hydrogel scaffold KI24RGDS stays in the meniscal lesion and facilitates meniscal repair and regeneration in an induced rabbit meniscal defect model. Full-thickness (2.0 mm diameter) cylindrical defects were introduced into the inner avascular zones of the anterior portions of the medial menisci of rabbit knees (n = 40). Right knee defects were left empty (control group) while the left knee defects were transplanted with peptide hydrogel (KI24RGDS group). Macroscopic meniscus scores were significantly higher in the KI24RGDS group than in the control group at 2, 4, and 8 weeks after surgery. Histological examinations including quantitative and qualitative scores indicated that compared with the control group, the reparative tissue in the meniscus was significantly enhanced in the KI24RGDS group at 2, 4, 8, and 12 weeks after surgery. Immunohistochemical staining showed that the reparative tissue induced by KI24RGDS at 12 weeks postimplantation was positive for Type I and II collagen. KI24RGDS is highly biocompatible and biodegradable, with strong stiffness, and a three dimensional structure mimicking native extracellular matrix and RGDS sequences that enhance cell adhesion and proliferation. This in vivo study demonstrated that KI24RGDS remained in the meniscal lesion and facilitated the repair and regeneration in a rabbit meniscal defect model., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Stem cell therapy has potential for the treatment of degenerative meniscus injuries; however, an optimal animal model has not been established. Basic and clinical research show that synovial mesenchymal stem cells (MSCs) promote meniscus repair. The purposes of this study were to create a novel meniscus injury model in microminipigs and to investigate the effectiveness of synovial MSCs on meniscus healing in this model. The posterior portion of the medial meniscus in microminipigs was punctuated 200 times with a 23G needle. Allogenic synovial MSC suspension was placed on the injury site for 10 min for transplantation. The meniscus was evaluated histologically and via sagittal magnetic resonance imaging (MRI), radial MRI reconstructed in three dimensional, and T2 mapping at 1 and 8 weeks. Proteoglycan content stained with safranin-o disappeared 1 week after treatment in both the MSC and control groups but increased at 8 weeks only in the MSC group. Histological scores at 8 weeks were significantly higher in the MSC group than in the control group (n = 6). At 8 weeks, the T2 values of the MSC group were significantly closer to those of a normal meniscus than were those of the control group. High signal intensity areas of the MRIs and positive areas stained with picrosirius red coincided with meniscal lesions. In conclusion, we created a novel meniscus injury model in microminipigs. Evaluation via histology, MRIs, and polarized microscopy showed that transplantation of synovial MSCs improved meniscus healing., (© 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

The meniscal ossicle is observed in clinical practice, yet there currently is limited information on its potential clinical significance. The purpose of this study was to assess the clinical presentation, imaging findings, and clinical treatment and outcomes of a series of patients identified as having a meniscal ossicle. An institutional database was reviewed to identify knees with a meniscal ossicle. Clinical presentation, magnetic resonance imaging (MRI), treatment, and outcomes were analyzed. Radiographs were graded using Kellgren-Lawrence (KL) scores. MRIs were reviewed for the presence and location of meniscal ossicles and additional knee pathology. Knee arthroplasty rates were recorded with the remaining patients contacted to obtain final International Knee Documentation Committee (IKDC) and Tegner's scores. Failure was defined as conversion to arthroplasty or failing IKDC score (< 75.4). Forty-five meniscal ossicles in 45 patients (26 males and 19 females) with a mean age of 51 years (standard deviation [SD] = 19.0) were included. Pain was the most common presenting symptom (89%). Forty-two patients (93%) had an associated meniscus root tear on MRI. Eighteen percent of patients that did not have an ossicle on initial imaging subsequently developed an ossicle. Mean KL grades progressed significantly from baseline of 1.84 (SD = 1.0) to 2.55 (SD = 0.93 p  < 0.01) on final follow-up. Thirty-nine percent of baseline radiographs showed KL grades of less than 2 compared with only 15% of follow-up radiographs ( p  = 0.04). Mean IKDC score obtained for patients ≤ 60 at an average follow-up of 3.1 years (SD = 3.2) was 65.2 (SD = 19.0). Eight out of 45 patients (18%) had progressed to total knee arthroplasty (TKA) by latest available follow-up. Sixty-two percent of patients met failure criteria at latest available follow-up. The meniscal ossicle is most commonly found in the posterior horn or root of the medial meniscus and is highly suggestive to be sequelae of a posterior root tear. Therefore, the presence of a meniscal ossicle should alert the orthopaedic surgeon to the high likelihood of the patient having a meniscus root tear. These patients have shown to have poor clinical outcomes and worsening arthritis., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Meniscus tear is one of the most familiar orthopedic injury, and it is also the leading cause of the dysfunction of knee joint. Recent efforts to improve the success rate of the meniscus repair surgery involve the addition of platelet-rich plasma (PRP). The aim of our experiment is to assess the clinical effects of arthroscopic repair of meniscal tears without or with PRP., Methods: This is a randomized and parallel-group superiority study. The study protocol is approved through the review committee of the corresponding institutions in PLA Army 80th Group Military Hospital. All patients will provide written informed consent to participate in the study. We implement our investigation on the basis of the ethical standards outlined in the Helsinki Declaration of 1964 and then report our outcomes according to the CONSORT statement of 2010. All the patients follow a same rehabilitation program. Patients are assessed at baseline (day before operation), 12 months and 24 months after the last time of injection; outcome assessments involve Ikeuchi score, Lysholm score, and the visual analogue scales for failure and pain rate. P value less than .05 indicates that there is statistical significance., Results: We suppose that arthroscopic PRP repair of meniscus tears results in improved pain and functional results owing to the release of bioactive molecules that may affect the healing of meniscus., Trial Registration: This study protocol was registered in Research Registry (researchregistry6175).

Purpose: The present study is a systematic review of a relatively unknown structure of the posterolateral corner of the knee, the meniscofibular ligament (MFL), aiming at summarizing and broadening current scientific knowledge regarding this ligament anatomy, function, imaging and injury., Materials and Methods: A systematic review was performed according to the PRISMA guidelines. Medline (PubMed) and Cochrane Library databases were reviewed for every kind of study reporting on the MFL through December 2019. Due to between-study differences in (anatomy, function, imaging, injury) examining the ligament, the findings were summarized from each study, but the results were not pooled., Results: The MFL is a ligament extending between the inferolateral portion of lateral meniscus, just anterior to the popliteus tendon, and the fibular head. It provides stability to the posterolateral corner of the knee joint, it can be demonstrated in magnetic resonance imaging and magnetic resonance arthrography and has a potential role in lateral meniscus injuries. Further research is required to clearly understand the prognosis and management of MFL injury., Conclusion: The current systematic review, focusing only on the MFL of the knee, summarizes the existing knowledge on anatomy, gross morphology, histology, function, biomechanics and imaging and contributes to the further understanding of the MFL.

Backgroud: To determine patient factors that lead to treatment of meniscal tears with osteoarthritis (OA) with knee arthroscopy (KA) or physical therapy only (PT-only); and to assess differences in clinical outcomes including the time to knee arthroplasty., Methods: Patients aged ≥ 45 years with OA at meniscal tear diagnosis were followed up from the date of surgery (KA) or first PT visit (PT-only) until partial/total knee replacement surgery, death, disenrollment, or end of study. Demographic and clinical characteristics were compared and used to derive propensity scores. A Cox proportional hazards model was used to estimate the risk of knee replacement surgery and greater healthcare utilization associated with KA vs. PT-only., Results: Among 7,026 patients (KA, 69%; PT-only, 31%), 27% had partial or total knee replacement surgery during follow-up. PT-only patients were older and more likely to be women and had more comorbidities. After accounting for differences between groups, the cumulative incidence of knee replacement was modestly but significantly higher for those who received KA than those who underwent PT-only (hazard ratio, 1.30; 95% confidence interval, 1.17-1.44; p < 0.001), although there was no significant difference in health service utilization, narcotic medication dispenses, or knee injections after initiating treatment., Conclusions: For patients with meniscal damage complicated by OA, those who underwent KA were 30% more likely to have partial or total knee replacement surgery at any given time than those who had PT alone., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2020 by The Korean Orthopaedic Association.)

Reduced impact loading or anti-gravity training has recently been introduced as a new tool in the rehabilitation of orthopaedic conditions that require restricted weight bearing. The purpose of this strategy is to speed up the functional rehabilitation while at the same time protect the healing structures from harmful effects associated with impact loading. Anti- gravity treadmills (AlterG ® ) and harness suspension devices seem to be the two most promising techniques. It is however today unclear how effective these devices are. The purpose of our study was therefore to perform a systematic literature review on the actual technology available and its effect on impact load reduction, as well as its effectiveness in accelerating functional recovery after meniscal and chondral injury to the knee. The results from our work demonstrate that only a limited number of studies are available, usually of moderate quality. The data suggest a variable effect on cartilage regeneration, and a potential for accelerated functional recovery in gait and running dynamics both with anti-gravity treadmill as well as suspension harness systems.

The objective of this study is to show the short-term clinical and radiological outcomes of concentrated bone marrow aspirate (CBMA) injection administered in combination with medial meniscus scaffold implantation. Twenty-three patients who received intra-articular CBMA injection in combination with polyurethane-based medial meniscus scaffold implantation were evaluated within the scope of this study. The International Knee Documentation Committee (IKDC) questionnaire and the Knee injury and Osteoarthritis Outcome Score (KOOS) were used to evaluate the results, and the visual analog scale was used to assess the pain scores. Magnetic resonance imaging (MRI) scans were obtained in the preoperative period and at postoperative months 1, 12, 24, and 36 to assess the scaffold position as well as chondral degeneration/damage in a comparative manner. MRI assessment was performed by using the modified Outerbridge scale for cartilage and the Genovese scoring system for the meniscal implant. Twenty-three patients who were included in the study were evaluated for a mean follow-up period of 38.3 months. Patients exhibited statistically significant improvement according to all scoring data from the preoperative period until the follow-up period. The mean postoperative extrusion at year 3 was 2.39 mm (distribution 2.30-2.56 mm). There was no significant difference in the distribution of the degree of chondral damage between the preoperative and 3-year follow-up periods. Four patients did not show any improvement nor had lower scores according to the assessment. Medial meniscus scaffold implantation combined with intra-articular CBMA injection resulted in a significant improvement in all functions and pain scores as well as a statistically significant clinical improvement in IKDC and KOOS values in the short-term follow-up. The Level of evidence for this study is IV., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose: The purpose of this systematic review is to evaluate the current literature and to assess the clinical outcomes following meniscal ramp lesion treatment and anterior cruciate ligament (ACL) reconstruction. A consensus of the treatment of this pattern of tears is still lacking., Methods: A systematic review of the literature was performed with a comprehensive search on Medline through PubMed, CINAHL, Cochrane, Embase and Google Scholar databases. The PRISMA 2009 flowchart and checklist were considered to edit the review. The included studies were evaluated based on indications, management, surgical technique and clinical results., Results: Seven studies (two level II and five level IV evidence) were identified that met inclusion criteria, including a total of 509 patients. The overall main follow-up was 23.6 months. Treatment failure occurred in 8.3% of patients receiving ACL repair and ramp lesion treatment. The repair of ramp lesion is the most used approach in the literature., Conclusion: There is a lack of literature focused on the management of ramp lesion and ACL injuries. The repair resulted in the most used approach with good clinical results and low failure rate. However, further high-quality studies evaluating the long-term outcomes of different surgical strategies are needed.

The stromal-cell-derived factor-1α (SDF-1) is well-known for playing important roles in the regeneration of tissue by enhancing cell migration. However, the effect of SDF-1 in meniscal healing remains unknown. The purpose of this study is to investigate the effects of intra-articular injection of SDF-1 on meniscus healing in a rat meniscal defect model. The intra-articular SDF-1 injection was performed at meniscectomy and one week later. Macroscopic and histological assessments of the reparative meniscus were conducted at one, two and six weeks after meniscectomy in rats. In the macroscopic evaluation, the SDF-1 group showed an increase in the size of the reparative meniscus at six weeks after meniscectomy compared to the phosphate-buffered saline (PBS) injection (no-treatment) group. Histological findings showed that intra-articular injection of SDF-1 enhanced the migration of macrophages to the site of the regenerative meniscus at one and two weeks after meniscectomy. CD68- and CD163-positive cells in the SDF-1 group at one week after meniscectomy were significantly higher than in the no-treatment group. CD163-positive cells in the SDF-1 group at two weeks were significantly higher than in the no-treatment group. At one week after meniscectomy, there were cells expressing mesenchymal-stem-cell-related markers in the SDF-1 group. These results indicate the potential of regenerative healing of the meniscus by SDF-1 injection via macrophage and mesenchymal stem cell accumulation. In the present study, intra-articular administration of SDF-1 contributed to meniscal healing via macrophage, CD90-positive cell and CD105-positive cell accumulation in a rat meniscal defect model. The SDF-1-CXCR4 pathway plays an important role in the meniscal healing process. For potential clinical translation, SDF-1 injection therapy seems to be a promising approach for the biological augmentation in meniscal injury areas to enhance healing capacity.

Objective: To evaluate progression of individual radiographic features 5 years following exercise therapy or arthroscopic partial meniscectomy as treatment for degenerative meniscal tear., Design: Randomized controlled trial including 140 adults, aged 35-60 years, with a magnetic resonance image verified degenerative meniscal tear, and 96% without definite radiographic knee osteoarthritis. Participants were randomized to either 12-weeks of supervised exercise therapy or arthroscopic partial meniscectomy. The primary outcome was between-group difference in progression of tibiofemoral joint space narrowing and marginal osteophytes at 5 years, assessed semi-quantitatively by the OARSI atlas. Secondary outcomes included incidence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis, medial tibiofemoral fixed joint space width (quantitatively assessed), and patient-reported outcome measures. Statistical analyses were performed using a full analysis set. Per protocol and as treated analysis were also performed., Results: The risk ratios (95% CI) for progression of semi-quantitatively assessed joint space narrowing and medial and lateral osteophytes for the surgery group were 0.89 (0.55-1.44), 1.15 (0.79-1.68) and 0.77 (0.42-1.42), respectively, compared to the exercise therapy group. In secondary outcomes (full-set analysis) no statistically significant between-group differences were found., Conclusion: The study was inconclusive with respect to potential differences in progression of individual radiographic features after surgical and non-surgical treatment for degenerative meniscal tear. Further, we found no strong evidence in support of differences in development of incident radiographic knee osteoarthritis or patient-reported outcomes between exercise therapy and arthroscopic partial meniscectomy., Trial Registration: www.clinicaltrials.gov (NCT01002794)., (Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Degenerative meniscal tear is a chronic disorder which presents with knee pain, swelling and loss of motion. It is currently unknown whether arthroscopic partial meniscectomy combined with medical exercise therapy is superior to isolated medical exercise therapy for degenerative meniscal tear., Objective: To determine if medical exercise therapy alone is as effective as arthroscopic partial meniscectomy combined with medical exercise therapy in treating degenerative meniscal tear., Method: Electronic searches were performed using MEDLINE, EMBASE, and the Cochrane Library Databases for all randomized studies. Two reviewers independently completed the literature screening, data extraction, and risk evaluation of bias. The outcome measures were visual analogue scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), range of motion, the Lysholm Knee Scoring Scale (LKSS), Knee injury and Osteoarthritis Outcome Score (KOOS) and postoperative complications. STATA 13.0 software was applied for meta-analysis., Result: Six randomized controlled trials (RCTs) were conducted, with 900 patients included. The present study revealed that there were significant differences between the two groups regarding the VAS at two months, as well as, WOMAC and range of motion. No significant differences were found in terms of LKSS, KOOS or postoperative complications., Limitations: (1) Only 6 RCTs were included in our meta-analysis and the sample sizes were small; (2) The follow-up period was too short in some included studies. Long-term follow-up studies should be conducted in the future; (3) Heterogeneity among the included studies was unavoidable due to different grade of degenerative meniscal tear and program of exercise. Heterogeneity was also caused by a variety of other factors. (4) Publication bias that came from the process of literature searching was unavoidable and was hard to overcome. (5) There are many other words which could yielded more studies (Ex. physiotherapy, physical therapy modalities, exercise therapy, rehabilitation, knee, placebo, groups, tibial meniscus, meniscus, arthroscopy, meniscectomy, partial meniscectomy, randomized controlled trial, controlled clinical trial, randomized, systematic review, and meta-analysis). Implications of key findings: This meta-analysis suggests that doctors can choose arthroscopic partial meniscectomy combined with medical exercise therapy for the treatment of degenerative meniscal tear., Conclusion: Arthroscopic partial meniscectomy combined with medical exercise therapy is effective in reducing pain and improving range of motion in the early postoperative period. Therefore, arthroscopic partial meniscectomy combined with medical exercise therapy may be recommended for the treatment of degenerative meniscal tear. Further research is necessary to determine the type, frequency, and duration of the best exercise program. Systematic review registration number: Reviewregistry884., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Objectives: The purpose of this study was to verify that exercise aimed at improving knee kinematics in early-stage knee osteoarthritis (OA) patients with medial meniscus posterior root tears (MMPRTs) reduces knee adduction angle during gait and prevents rapid cartilage degeneration in the medial compartment of the knee. Methods: Subjects were randomly assigned to an adapting alignment exercise (AAE) group, with the goal of improving knee kinematics, and a muscle training and exercise (MTE) group. Before the start of the six-month intervention and following its completion, we performed an analysis of knee kinematics during gait using a 3D-to-2D registration technique and identified the area of cartilage degeneration using MRI T2 mapping. Results: The amount of change between pre- and post-intervention measurements of the maximum angle of adduction was 0.48° (95% CI: -0.14, 1.09) in the MTE group and -0.40° (-0.84, 0.04) in the AAE group ( p  = .039). The amount of change in the area of cartilage degeneration according to MRI T2 mapping expressed as MTE/AAE group was 7.7 mm 2 (-0.4, 15.8)/-2.7 mm 2 (-10.8, 5.3) at the posterior knee ( p  = .043). Conclusion: AAE could be a potential treatment method that improves the natural course of knee OA with MMRPTs.

Objective: The present study was undertaken to evaluate changes in knee magnetic resonance imaging (MRI) findings over the course of 18 months in subjects with osteoarthritic change and meniscal tear treated with arthroscopic partial meniscectomy (APM) or nonoperatively with physical therapy (PT)., Methods: We used 18-month follow-up data from the Meniscal Tear in Osteoarthritis Research Trial. MRI results were read with reference to the MRI Osteoarthritis Knee Score. We focused on 18-month change in bone marrow lesions (BMLs), cartilage thickness, cartilage surface area, osteophyte size, effusion-synovitis, and Hoffa-synovitis. We used multinomial logistic regression to assess associations between MRI-based changes in each feature and treatment type., Results: A total of 351 subjects were randomized, and 225 had both baseline and 18-month MRI results. In both treatment groups, patients experienced substantial changes in several MRI-based markers. In 60% of the APM group, versus 33% of the PT group, cartilage surface area damage advanced in ≥2 subregions (adjusted odds ratio 4.2 [95% confidence interval 2.0-9.0). Patients who underwent APM also had greater advancement in scores for osteophytes and effusion-synovitis. We did not find significant associations between treatment type and change in cartilage thickness, BMLs, or Hoffa-synovitis., Conclusion: This cohort of patients with meniscal tear and osteoarthritis showed marked advancement in MRI-based features over 18 months. Patients treated with APM showed more advancement in some features compared to those treated nonoperatively. The clinical relevance of these early findings is unknown and requires further study., (© 2019, American College of Rheumatology.)

Objectives: To examine whether physical therapy (PT) is cost-effective compared with arthroscopic partial meniscectomy (APM) in patients with a non-obstructive meniscal tear, we performed a full trial-based economic evaluation from a societal perspective. In a secondary analysis-this paper-we examined whether PT is non-inferior to APM., Methods: We recruited patients aged 45-70 years with a non-obstructive meniscal tear in nine Dutch hospitals. Resource use was measured using web-based questionnaires. Measures of effectiveness included knee function using the International Knee Documentation Committee (IKDC) and quality-adjusted life-years (QALYs). Follow-up was 24 months. Uncertainty was assessed using bootstrapping techniques. The non-inferiority margins for societal costs, the IKDC and QALYs, were €670, 8 points and 0.057 points, respectively., Results: We randomly assigned 321 patients to PT (n=162) or APM (n=159). PT was associated with significantly lower costs after 24 months compared with APM (-€1803; 95% CI -€3008 to -€838). The probability of PT being cost-effective compared with APM was 1.00 at a willingness to pay of €0/unit of effect for the IKDC (knee function) and QALYs (quality of life) and decreased with increasing values of willingness to pay. The probability that PT is non-inferior to APM was 0.97 for all non-inferiority margins for the IKDC and 0.89 for QALYs., Conclusions: The probability of PT being cost-effective compared with APM was relatively high at reasonable values of willingness to pay for the IKDC and QALYs. Also, PT had a relatively high probability of being non-inferior to APM for both outcomes. This warrants further deimplementation of APM in patients with non-obstructive meniscal tears., Trial Registration Numbers: NCT01850719 and NTR3908., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: all authors had financial support from The Netherlands Organisation for Health Research and Development (in Dutch: ZonMw) for the submitted work; the Achmea Healthcare Foundation (in Dutch Stichting Achmea Gezonheidszorg fonds) and the foundation of medical research at the OLVG, Amsterdam, the Netherlands; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.