The APC/C targets the Cep152-Cep63 complex at the centrosome to regulate mitotic spindle assembly.

The control of protein abundance is a fundamental regulatory mechanism during mitosis. The anaphase-promoting complex/cyclosome (APC/C) is the main protein ubiquitin ligase responsible for the temporal regulation of mitotic progression. It has been proposed that the APC/C might fulfil other functions, including assembly of the mitotic spindle. Here, we show that the APC/C localizes to centrosomes, the organizers of the eukaryotic microtubule cytoskeleton, specifically during mitosis. Recruitment of the APC/C to spindle poles requires the centrosomal protein Cep152, and we identified Cep152 as both an APC/C interaction partner and an APC/C substrate. Previous studies have shown that Cep152 forms a complex with Cep57 and Cep63. The APC/C-mediated ubiquitylation of Cep152 at the centrosome releases Cep57 from this inhibitory complex and enables its interaction with pericentrin, a critical step in promoting microtubule nucleation. Thus, our study extends the function of the APC/C from being a regulator of mitosis to also acting as a positive governor of spindle assembly. The APC/C thereby integrates control of these two important processes in a temporal manner.

The role of autologous bone grafting in matrix-associated autologous chondrocyte implantation at the knee: Results from the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: To investigate whether concomitant autologous bone grafting adversely affects clinical outcome and graft survival after matrix-associated autologous chondrocyte implantation (M-ACI). METHODS: The present study examines registry data of patients who underwent M-ACI with or without autologous bone grafting for large-sized chondral or osteochondral defects. Propensity score matching was performed to exclude potential confounders. A total of 215 patients with similar baseline characteristics were identified. Clinical outcome was assessed at the time of surgery and at 6, 12, 24, 36 and 60 months using the Knee Injury and Osteoarthritis Outcome Score (KOOS). KOOS change, clinical response rate, KOOS subcomponents and failure rate were determined. RESULTS: Patients treated with M-ACI and autologous bone grafting achieved comparable clinical outcomes compared with M-ACI alone. At 24 months postoperatively, the patient-reported outcome (PRO) of patients treated with M-ACI and autologous bone grafting was even significantly better as measured by KOOS (74.9 ± 18.8 vs. 79.2 ± 15.4; p = 0.043). However, the difference did not exceed the minimal clinically important difference (MCID). In patients with M-ACI and autologous bone grafting, a greater change in KOOS relative to baseline was observed at 6 (9.3 ± 14.7 vs. 15.0 ± 14.7; p = 0.004) and 12 months (12.6 ± 17.2 vs. 17.7 ± 14.6; p = 0.035). Overall, a high clinical response rate was observed in both groups at 24 months (75.8% vs. 82.0%; p = n.s.). The estimated survival at the endpoint of reoperation for any reason was 82.1% (SD 2.8) at 8.4 years for isolated M-ACI and 88.7% (SD 2.4) at 8.2 years for M-ACI with autologous bone grafting (p = 0.039). CONCLUSIONS: Even in the challenging cohort of large osteochondral defects, the additional treatment with autologous bone grafting leads to remarkably good clinical outcomes in patients treated with M-ACI. In fact, they tend to benefit more from surgery, have lower revision rates and achieve clinical response rates earlier. Subchondral bone management is critical to the success of M-ACI and should be addressed in the treatment of borderline defects. LEVEL OF EVIDENCE: Level III.

Females show worse functional outcome and quality of life compared to males 2 years after meniscus surgery: Data analysis from the German Arthroscopy Registry.

PURPOSE: The purpose of this study was to investigate the impact of sex on knee function, activity and quality of life following meniscus surgery using data from the German Arthroscopy Registry. METHODS: This is a retrospective cohort study with data collected between 2017 and 2022. Patient-reported outcome measures (PROMs), namely Knee Injury and Osteoarthritis Outcome Score (KOOS), EuroQol Visual Analogue Scale (EQ Scale), and Marx Activity Rating Scale (MARS), were collected preoperatively and at 6, 12 and 24 months postoperatively. Data were analysed to examine differences between male and female patients regarding PROMs, pre-existing conditions, meniscus lesion types and surgical treatments. RESULTS: A total of 1106 female (36.6%) and 1945 male patients (63.7%) were included. Males were significantly younger than females and had a higher body mass index. Overall, there were four times more medial meniscus lesions (MMLs) (77.5%) than lateral meniscus lesions (LMLs) (27.9%). Degenerative LMLs were more frequent in females, while traumatic LMLs were more common in males. Frequencies of traumatic and degenerative MMLs were similar among males and females. Males had higher absolute KOOS irrespective of treatment or meniscus lesion type. Meniscus repair resulted in similar improvements in ΔKOOS for both sexes, while meniscus resection exhibited higher absolute KOOS for males at each time point. Males generally had higher EQ Scale and MARS than females. CONCLUSION: Greater improvements in knee function, activity and quality of life were observed in males. While MMLs appear to be comparable among sexes, the nature of LML differed significantly. These results may help surgeons to refine patient selection for specific treatments to improve overall clinical outcomes. LEVEL OF EVIDENCE: Level III.

Anterior cruciate ligament injuries in elite ski jumping reliably allow return to competition but severely affect future top performance.

PURPOSE: In recent years, anterior cruciate ligament (ACL) injuries have been frequently observed in ski jumping. However, available data in this discipline are very scarce. Therefore, the purpose of this study was to investigate whether an ACL injury in elite-level ski jumping limits the performance level after ACL reconstruction (ACLR). METHODS: Both male and female elite-level ski jumpers from five national A-teams who suffered an ACL injury were identified retrospectively by searching available media reports and Fédération Internationale de Ski (FIS) database. World Cup (WC) results and time-out-of-competition before ACL injury and after ACLR were compared. Only athletes who suffered the injury during or after the 2009-2010 season and who participated in at least one WC competition before the injury were included in this study. The level of athletes' performance from two full seasons before until three seasons after the injury was compared. RESULTS: Eighteen elite-level ski jumpers (11 males/seven females) were eligible for the study. All male and four female athletes returned to professional competition after ACLR. One female athlete ended her career due to prolonged recovery and two have not yet recovered due to a recent injury. The mean return-to-competition (RTC) time was 14.6 months in males and 13.5 months in females. The mean WC placement decreased after the ACL injury: two seasons before injury the mean position was 17.9 ± 11.0 (n = 12), one season before it was 22.4 ± 12.8 (n = 15). After recovery, the mean placement in seasons 1-3 was: 26.4 ± 8.9 (n = 7), 25.7 ± 10.3 (n = 13), 33.6 ± 12.2 (n = 10) (p = 0.008). Among the athletes returning to competition, only six males and three females reached their preinjury level and only one male and one female (compared to seven males and three females preinjury) reached an individual top-3 placement after ACLR, accounting for less than 10% of podiums compared to preinjury. CONCLUSION: Only 60% of the professional ski jumpers reached the preinjury level and less than 15% reached a top-3 placement after the ACL injury. These results support the fact that ACL tear during a ski jumping career may be a significant factor limiting high-level performance. In terms of clinical relevance, the findings implicate the need to analyse the reasons of these very low rates of return to elite-level performance, to analyse ACL injury and RTC rates at lower levels of performance and to develop specific prevention strategies in order to reduce the number of ACL injuries in this sport. LEVEL OF EVIDENCE: Level IV.

Corticosteroid injections for the treatment of osteoarthritis present a wide spectrum of effects ranging from detrimental to disease-modifying: A systematic review of preclinical evidence by the ESSKA Orthobiologic Initiative.

PURPOSE: Aim of this systematic review of preclinical evidence was to determine the effects of intra-articular corticosteroid (CS) injections in joints affected by osteoarthritis (OA). METHODS: A systematic review was performed on animal studies evaluating intra-articular CS injections for OA joints. The search was performed on PubMed, Cochrane, and Web of Science databases. A synthesis of the results was performed investigating CS effects by evaluating studies comparing CS with control groups. Morphological, histological, immunohistochemistry evaluations, clinical outcomes, biomarkers and imaging results were evaluated. The risk of bias was assessed according to the Systematic Review Centre for Laboratory Animal Experimentation's tool. RESULTS: Thirty-two articles analysing CS effects in OA animal models were included (1079 joints), 18 studies on small and 14 on large animals. CS injections showed overall positive effects in at least one of the outcomes in 68% of the studies, while 16% reported a deleterious effect. CS improved cartilage and synovial outcomes in 68% and 60% of the studies, but detrimental effects were documented in 11% and 20% of the studies, respectively. Clinical parameters evaluated in terms of pain, lameness or joint swelling improved in 63% of the studies but deteriorated in 13%. Evidence is limited on imaging and biomarkers results, as well as on the best CS type, dose, formulation and injection protocol. The risk of bias assessment revealed a 28% low and an 18% high risk of bias. CONCLUSION: Intra-articular CS injections induced a wide range of results on OA joints in experimental animal models, from disease-modifying and positive effects on pain and joint function at short-term evaluation to the lack of benefit or even negative effects. This underlines the need to identify more specific indications and treatment modalities to avoid possible detrimental effects while maximising the anti-inflammatory properties and the benefits of intra-articular CS in OA joints. LEVEL OF EVIDENCE: Level II.

The use of injectable orthobiologics for knee osteoarthritis: A European ESSKA-ORBIT consensus. Part 1-Blood-derived products (platelet-rich plasma).

PURPOSE: The aim of this European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) consensus is to provide recommendations based on evidence and expert opinion to improve indications, decision-making and administration-related aspects when using blood-derived orthobiologics (for simplicity indicated as PRP-platelet-rich plasma-with PRP being the most common product) for the management of knee osteoarthritis (OA). METHODS: Leading European expert clinicians and scientists were divided into a steering group, a rating group and a peer review group. The steering group prepared 28 question-statement sets divided into three sections: PRP rationale and indications, PRP preparation and characterisation and PRP protocol. The quality of the statements received grades of recommendation ranging from A (high-level scientific support) to B (scientific presumption), C (low-level scientific support) or D (expert opinion). The question-statement sets were then evaluated by the rating group, and the statements scored from 1 to 9 based on their degree of agreement with the statements produced by the steering group. Once a general consensus was reached between the steering and rating groups, the document was submitted to the peer review group who evaluated the geographic adaptability and approved the document. A final combined meeting of all the members of the consensus was held to produce the official document. RESULTS: The literature review on the use of blood-derived products for knee OA revealed that 9 of 28 questions/statements had the support of high-level scientific literature, while the other 19 were supported by a medium-low scientific quality. Three of the 28 recommendations were grade A recommendations: (1) There is enough preclinical and clinical evidence to support the use of PRP in knee OA. This recommendation was considered appropriate with a strong agreement (mean: 8). (2) Clinical evidence has shown the effectiveness of PRP in patients for mild to moderate degrees of knee OA (KL ≤ 3). This recommendation was considered appropriate with a strong agreement (mean: 8.1). (3) PRP injections have been shown to provide a longer effect in comparison to the short-term effect of CS injections. They also seem to provide a safer use profile with less potential related complications. This recommendation was considered appropriate with a very strong agreement (mean: 8.7). Six statements were grade B recommendations, 7 were grade C and 12 were grade D. The mean rating score was 8.2 ± 0.3. CONCLUSIONS: The consensus group reached a high level of agreement on all the questions/statements despite the lack of clear evidence for some questions. According to the results from this consensus group, given the large body of existing literature and expert opinions, PRP was regarded as a valid treatment option for knee OA and as a possible first-line injectable treatment option for nonoperative management of knee OA, mainly for KL grades 1-3. LEVEL OF EVIDENCE: Level II.

Platelet-rich plasma injections for the management of knee osteoarthritis: The ESSKA-ICRS consensus. Recommendations using the RAND/UCLA appropriateness method for different clinical scenarios.

PURPOSE: The aim of this consensus was to develop evidence- and expert-based patient-focused recommendations on the appropriateness of intra-articular platelet-rich plasma (PRP) injections in different clinical scenarios of patients with knee osteoarthritis (OA). METHODS: The RAND/UCLA Appropriateness Method was used by the European Society of Sports Traumatology, Knee Surgery, and Arthroscopy (ESSKA), as well as the International Cartilage Regeneration and Joint Preservation Society (ICRS) to reach a consensus and produce recommendations for specific patient categories combining best available scientific evidence with the collective judgement of a panel of experts. RESULTS: Scenarios were defined based on first treatment vs first injective treatment vs second injective treatment, age (<50/50-65/66-80/>80), tibiofemoral vs patellofemoral involvement, OA level (Kellgren-Lawrence/KL 0-I/II-III/IV), and joint effusion (dry knee, minor-mild or major effusion). Out of 216 scenarios, in 84 (38.9%) the indication was considered appropriate, in 9 (4.2%) inappropriate and in 123 (56.9%) uncertain. The parameters associated with the highest consensus were PRP use after failed injective treatments (62.5%), followed by PRP after failed conservative treatments and KL 0-III scenarios (58.3%), while the highest uncertainty was found for PRP use as first treatment and KL IV OA (91.7% and 87.5% of uncertain scenarios, respectively). CONCLUSION: This ESSKA-ICRS consensus established recommendations on the appropriateness or inappropriateness of PRP injections for the treatment of knee OA, providing a useful reference for clinical practice. PRP injections are considered appropriate in patients aged ≤80 years with knee KL 0-III OA grade after failed conservative non-injective or injective treatments, while they are not considered appropriate as first treatment nor in KL IV OA grade. LEVEL OF EVIDENCE: Level I.

An anteromedial stabilization procedure has the most protective effect on the anterior cruciate ligament in tibial external rotation. A human knee model study.

INTRODUCTION: Anterior cruciate ligament (ACL) reconstruction remains associated with the risk of re-rupture and persisting rotational instability. Additional extraarticular anterolateral stabilization procedures stabilize the tibial internal rotation and lead to lower ACL failure rate and improved knee stability. However, data for additional stabilization of tibial external rotation is lacking and the importance of an anteromedial stabilization procedure is less well evaluated. Aim of this study is to investigate the influence of an extraarticular anteromedial stabilization procedure for the stabilization of the tibial external rotation and protection of the ACL from these rotational forces. METHODS: Internal and external rotations of the tibia were applied to a finite element (FE) model with anatomical ACL, posterior cruciate ligament (PCL), lateral collateral ligament (LCL), medial collateral ligament (MCL) and intact medial and lateral meniscus. Five additional anatomic structures (Anteromedial stabilization/anteromedial ligament, AML, augmented superficial medial collateral ligament, sMCL, posterior oblique ligament, POL, anterolateral ligament, ALL, and popliteal tendon, PLT) were added to the FE model separately and then combined. The force histories within all structures were measured and determined for each case. RESULTS: The anteromedial stabilization or imaginary AML was the main secondary stabilizer of tibial external rotation (90% of overall ACL force reduction). The AML reduced the load on the ACL by 9% in tibial external rotation which could not be achieved by an augmented sMCL (-1%). The AML had no influence in tibial internal rotation (-1%). In the combined measurements with all additional structures (AML, ALL, PLT, POL) the load on the ACL was reduced by 10% in tibial external rotation. CONCLUSION: This study showed that an additional anteromedial stabilization procedure secures the tibial external rotation and has the most protective effect on the ACL during these external rotational forces.

Comparison between dedicated MRI and symphyseal fluoroscopic guided contrast agent injection in the diagnosis of cleft sign in athletic groin pain and association with pelvic ring instability.

OBJECTIVE: To compare dedicated MRI with targeted fluoroscopic guided symphyseal contrast agent injection regarding the assessment of symphyseal cleft signs in men with athletic groin pain and assessment of radiographic pelvic ring instability. METHODS: Sixty-six athletic men were prospectively included after an initial clinical examination by an experienced surgeon using a standardized procedure. Diagnostic fluoroscopic symphyseal injection of a contrast agent was performed. Additionally, standing single-leg stance radiography and dedicated 3-Tesla MRI protocol were employed. The presence of cleft injuries (superior, secondary, combined, atypical) and osteitis pubis was recorded. RESULTS: Symphyseal bone marrow edema (BME) was present in 50 patients, bilaterally in 41 patients and in 28 with an asymmetrical distribution. Comparison of MRI and symphysography was as followed: no clefts: 14 cases (MRI) vs. 24 cases (symphysography), isolated superior cleft sign: 13 vs. 10, isolated secondary cleft sign: 15 vs. 21 cases and combined injuries: 18 vs. 11 cases. In 7 cases a combined cleft sign was observed in MRI but only an isolated secondary cleft sign was visible in symphysography. Anterior pelvic ring instability was observed in 25 patients and was linked to a cleft sign in 23 cases (7 superior cleft sign, 8 secondary cleft signs, 6 combined clefts, 2 atypical cleft injuries). Additional BME could be diagnosed in 18 of those 23. CONCLUSION: Dedicated 3-Tesla MRI outmatches symphysography for purely diagnostic purposes of cleft injuries. Microtearing at the prepubic aponeurotic complex and the presence of BME is a prerequisite for the development of anterior pelvic ring instability. CLINICAL RELEVANCE STATEMENT: For diagnostic of symphyseal cleft injuries dedicated 3-T MRI protocols outmatch fluoroscopic symphysography. Prior specific clinical examination is highly beneficial and additional flamingo view x-rays are recommended for assessment of pelvic ring instability in these patients. KEY POINTS: • Assessment of symphyseal cleft injuries is more accurate by use of dedicated MRI as compared to fluoroscopic symphysography. • Additional fluoroscopy may be important for therapeutic injections. • The presence of cleft injury might be a prerequisite for the development of pelvic ring instability.

The German Arthroscopy Registry DART: what has happened after 5 years?

PURPOSE: The German Arthroscopy Registry (DART) has been initiated in 2017 with the aim to collect real-life data of patients undergoing knee, shoulder, hip or ankle surgery. The purpose of this study was to present an overview of the current status and the collected data thus far. METHODS: Data entered between 11/2017 and 01/2022 were analyzed. The number of cases (each case is defined as a single operation with or without concomitant procedures) entered for each joint, follow-up rates and trends between different age groups (18-29 years, 30-44 years, 45-64 years, ≥ 65 years) and across genders, and quality of life improvement (pre- vs. 1 year postoperative EQ visual analogue scale [EQ-VAS]) for frequently performed procedures (medial meniscus repair [MMR] vs. rotator cuff repair [RCR] vs. microfracturing of the talus [MFX-T]) were investigated. RESULTS: Overall, 6651 cases were entered into DART, forming three distinct modules classified by joint (5370 knee, 1053 shoulder and 228 ankle cases). The most commonly entered procedures were: knee: partial medial meniscectomy (n = 2089), chondroplasty (n = 1389), anterior cruicate ligament reconstruction with hamstring autograft (n = 880); shoulder: sub acromial decompression (n = 631), bursectomy (n = 385), RCR (n = 359); ankle: partial synovectomy (n = 117), tibial osteophyte resection (n = 72), loose body removal (n = 48). In the knee and shoulder modules, middle-aged patients were the predominant age group, whereas in the ankle module, the youngest age group was the most frequent one. The two oldest age groups had the highest 1-year follow-up rates across all modules. In the knee and shoulder module, 1-year follow-up rates were higher in female patients, whereas follow-up rates were higher in male patients in the ankle module. From pre- to 1-year postoperative, MFX-T (EQ-VAS: 50.0 [25-75% interquartile range: 31.8-71.5] to 75.0 [54.3-84.3]; ∆ + 25.0) led to a comparably larger improvement in quality of life than did MMR (EQ-VAS: 70.0 [50.0-80.0] to 85.0 [70.0-94.0]; ∆ + 15.0) or RCR (EQ-VAS: 67.0 [50.0-80.0] to 85.0 [70.0-95.0]; ∆ + 18.0). CONCLUSION: DART has been sufficiently established and collects high-quality patient-related data with satisfactory follow-up allowing for a comprehensive analysis of the collected data. The current focus lies on improving patient enrolment and follow-up rates as well as initiating the hip module.

The posterior cruciate ligament-posterior femoral cortex angle (PCL-PCA) and the lateral collateral ligament (LCL) sign are useful parameters to indicate the progression of knee decompensation over time after an ACL injury.

PURPOSE: The posterior cruciate ligament-posterior cortex angle (angle between the most vertical part of the anterolateral PCL bundle and the posterior diaphyseal cortex of the femur; PCL-PCA) is the most accurate approach to describe the PCL buckling phenomenon observed in anterior cruciate ligament (ACL)-deficient knees. The aim of this study was to determine whether the PCL-PCA is associated with chronicity of the ACL rupture, the meniscal status, preoperative knee laxity or imaging signs such as the lateral collateral ligament (LCL) sign or the posterior tibial slope (PTS) in ACL-injured knees. METHODS: Patients with a primary ACL reconstruction (ACLR) after physeal closure were selected retrospectively from a hospital-based ACL registry from 2015 to 2021. Exclusion criteria were: previous ipsilateral/contralateral knee surgery, previous ipsilateral ACL or meniscal tear, ipsilateral PCL and/or collateral ligament injuries or tibial plateau fracture. The ACL deficiency was defined as chronic if time from injury to MRI was > 6 months. The meniscal status was assessed during ACLR, separately for the medial and lateral meniscus, and classified into no tear, minor or major unstable tear. The MRI analyses included the assessment of the PCL-PCA and the LCL sign. PTS was assessed from the lateral plain radiographs of the injured knee. The side-to-side difference in anterior tibial translation (ATT) at 200N was obtained with the GNRB. RESULTS: Eighty-two patients (forty-eight males/thirty-four females) were included in this study. The median PCL-PCA was 16.2° (Q1-Q3: 10.6-24.7) and differed between acute (18.4°) and chronic (10.7°) injuries (p < 0.01). The median PCL-PCA was significantly lower (- 4.6°) in patients with a positive LCL sign (p = 0.03) No significant association could be found between PCL-PCA and meniscal status, PTS or preoperative anterior knee laxity (Lachman, pivot shift and ATT in millimetres). CONCLUSION: The PCL-PCA was significantly lower in chronic ACL injuries and in patients with a positive LCL sign, indicating a higher buckling phenomenon of the PCL in these patients. These results support the fact that PCL-PCA and the LCL sign may be useful parameters to indicate the progression of knee decompensation over time after an ACL injury, and therefore may constitute a helpful tool to optimise treatment choice and timing of ACL reconstruction if necessary. LEVEL OF EVIDENCE: III.

Knot tying in arthroplasty and arthroscopy causes lesions to surgical gloves: a potential risk of infection.

PURPOSE: Recent studies have shown that the incidence of glove lesions during arthroscopy is much lower than that during primary and revision arthroplasty. However, the rate of glove damage after knot tying has not yet been systematically recorded. Therefore, the aim of the study was to determine the impact of surgical knot tying on glove integrity. It was hypothesized that knot tying increases the rate of glove damage, especially in arthroscopic surgery, which could be of special relevance in the treatment of rotator cuff tears. METHODS: Gloves that were changed immediately before suturing and only worn during knot tying were investigated for their integrity by means of water tightening test according to EN455. A total of 234 gloves from 40 total hip arthroplasties (THAs), 42 total knee arthroplasties (TKAs) and 36 rotator cuff repairs (RCRs) were collected. A bacterial pass-through test (BPTT) on glove lesions was performed under simulated sterile surgical conditions for 3 surgeons after a wear duration of 45 min. RESULTS: Glove damage by knot tying occurred in 25% of THA, 36.6% of TKA and 25% of RCR surgeries. In THA, the pulling hand (PH) was affected in 46.2%, and the main area of damage (15.4%) was detected on the tip of the middle finger; in TKAs the PH was damaged in 75%, and in RCRs the PH was affected in 66.7%, with most of the lesions (20% each) occurring on the tip of the index finger and the ring finger. The BPTT showed Staphylococcus hominis and Bacillus cereus. CONCLUSION: Intraoperative knot tying causes damage to gloves, which is of special relevance for arthroscopic surgery. Whereas knot tying is only partly responsible for glove damage in arthroplasty, the general rate of glove damage in arthroscopic surgery is low without knot tying. The surgical knot tying process must be understood as a possible damaging impact on the glove. Therefore, single gloving is not recommended, which is especially important in arthroscopic surgery, where double gloving is not yet standard. LEVEL OF EVIDENCE: IV.

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 2: bone marrow-derived cell-based injectable therapies.

PURPOSE: Aim of this systematic review was to determine if bone marrow-derived cell-based injectable therapies induce disease-modifying effects in joints affected by osteoarthritis (OA) in animal models. METHODS: A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical animal studies comparing injectable bone marrow-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE's tool. RESULTS: Fifty-three studies were included (1819 animals) with an increasing publication trend over time. Expanded cells were used in 48 studies, point-of-care products in 3 studies, and both approaches were investigated in 2 studies. Among the 47 studies presenting results on the disease-modifying effects, 40 studies (85%) reported better results with bone marrow-derived products compared to OA controls, with positive findings evident in 14 out of 20 studies (70%) in macroscopic assessment, in 30 out of 41 studies (73%) in histological assessment, and in 10 out of 13 studies (77%) in immunohistochemical evaluations. Clinical evaluations showed positive results in 7 studies out of 9 (78%), positive imaging results in 11 studies out of 17 (65%), and positive biomarker results in 5 studies out of 10 (50%). While 36 out of 46 studies (78%) reported positive results at the cartilage level, only 3 out of 10 studies (30%) could detect positive changes at the synovial level. The risk of bias was low in 42% of items, unclear in 50%, and high in 8%. CONCLUSION: This systematic review of preclinical studies demonstrated that intra-articular injections of bone marrow-derived products can induce disease-modifying effects in the treatment of OA, slowing down the progression of cartilage damage with benefits at macroscopic, histological, and immunohistochemical levels. Positive results have been also observed in terms of clinical and imaging findings, as well as in the modulation of inflammatory and cartilage biomarkers, while poor effects have been described on the synovial membrane. These findings are important to understand the potential of bone marrow-derived products and to guide further research to optimise their use in the clinical practice. LEVEL OF EVIDENCE: II.

Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies.

PURPOSE: The aim of this systematic review was to determine if adipose tissue-derived cell-based injectable therapies can induce disease-modifying effects in joints affected by osteoarthritis (OA). METHODS: A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical studies comparing injectable adipose-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE's tool. RESULTS: Seventy-one studies were included (2,086 animals) with an increasing publication trend over time. Expanded cells were used in 65 studies, 3 studies applied point of care products, and 3 studies investigated both approaches. Overall, 48 out of 51 studies (94%) reported better results with adipose-derived products compared to OA controls, with positive findings in 17 out of 20 studies (85%) in macroscopic, in 37 out of 40 studies (93%) in histological, and in 22 out of 23 studies (96%)  in immunohistochemical evaluations. Clinical and biomarker evaluations showed positive results in 14 studies out of 18 (78%) and 12 studies out of 14 (86%), while only 9 studies out of 17 (53%) of the imaging evaluations were able to detect differences versus controls. The risk of bias was low in 38% of items, unclear in 51%, and high in (11%). CONCLUSION: The current preclinical models document consistent evidence of disease-modifying effects of adipose-derived cell-based therapies for the treatment of OA. The high heterogeneity of the published studies highlights the need for further targeted research to provide recommendations on the optimal methodologies for a more effective application of these injective therapies for the treatment of OA in clinical practice. LEVEL OF EVIDENCE: II.

Biological intra-articular augmentation for osteotomy in knee osteoarthritis: strategies and results : A systematic review of the literature from the ESSKA Orthobiologics Initiative.

PURPOSE: To assess whether there is evidence supporting the use of augmentation strategies, either cartilage surgical procedures or injective orthobiologic options, to improve the results of osteotomies in knees with osteoarthritis (OA). METHODS: A systematic review of the literature was performed on the PubMed, Web of Science and the Cochrane databases in January 2023 on osteotomies around the knee associated with augmentation strategies (either cartilage surgical procedures or injective orthobiologic options), reporting clinical, radiological, or second-look/histological outcomes at any follow-up. The methodological quality of the included studies was assessed with the Coleman Methodology Score (CMS). RESULTS: Out of the 7650 records identified from the databases, 42 articles were included for a total of 3580 patients and 3609 knees treated; 33 articles focused on surgical treatments and 9 on injective treatments performed in association with knee osteotomy. Out of the 17 comparative studies with surgical augmentation, only 1 showed a significant clinical benefit of an augmentation procedure with a regenerative approach. Overall, other studies showed no differences with reparative techniques and even detrimental outcomes with microfractures. Regarding injective procedures, viscosupplementation showed no improvement, while the use of platelet-rich plasma or cell-based products derived from both bone marrow and adipose tissue showed overall positive tissue changes which translated into a clinical benefit. The mean modified CMS score was 60.0 ± 12.1. CONCLUSION: There is no evidence to support the effectiveness of cartilage surgical treatments combined with osteotomies in terms of pain relief and functional recovery of patients affected by OA in misaligned joints. Orthobiologic injective treatments targeting the whole joint environment showed promising findings. However, overall the available literature presents a limited quality with only few heterogeneous studies investigating each treatment option. This ORBIT systematic analysis will help surgeons to choose their therapeutic strategy according to the available evidence, and to plan further and better studies to optimize biologic intra-articular osteotomy augmentation. LEVEL OF EVIDENCE: Level IV.

The awareness of injury prevention programmes is insufficient among French- and German-speaking sports medicine communities in Europe.

PURPOSE: Evaluate the current state of sports injury prevention perception, knowledge and practice among sports medicine professionals located in Western Europe and involved in injury prevention. METHODS: Members of two different sports medicine organizations (GOTS and ReFORM) were invited to complete a web-based questionnaire (in German and in French, respectively) addressing perception, knowledge and implementation of sports injury prevention through 22 questions. RESULTS: 766 participants from a dozen of countries completed the survey. Among them, 43% were surgeons, 23% sport physicians and 18% physiotherapists working mainly in France (38%), Germany (23%) and Belgium (10%). The sample rated the importance of injury prevention as "high" or "very high" in a majority of cases (91%), but only 54% reported to be aware of specific injury prevention programmes. The French-speaking world was characterized by lower levels of reported knowledge, unfamiliarity with existing prevention programmes and less weekly time spent on prevention as compared to their German-speaking counterparts. Injury prevention barriers reported by the respondents included mainly insufficient expertise, absence of staff support from sports organizations and lack of time. CONCLUSION: There is a lack of awareness regarding injury prevention concepts among sports medicine professionals of the European French- and German-speaking world. This gap varied according to the professional occupation and working country. Relevant future paths for improvement include specific efforts to build awareness around sports injury prevention. LEVEL OF EVIDENCE: Level IV.

Management of anterior cruciate ligament revision in adults: the 2022 ESSKA consensus part I-diagnostics and preoperative planning.

PURPOSE: The aim of this ESSKA consensus is to give recommendations based on evidence and expert opinion to improve diagnosis, preoperative planning, indication and surgical strategy in ACL revision. METHODS: The European expert surgeons and scientists were divided into four groups to participate in this consensus. A "literature group" (four surgeons); "steering group" (14 surgeons and scientists); "rating group" (19 surgeons) and finally "peer review group" (51 representatives of the ESSKA-affiliated national societies from 27 countries). The steering group prepared eighteen question-answer sets. The quality of the answers received grades of recommendation ranging from A (high-level scientific support), to B (scientific presumption), C (low level scientific support) or D (expert opinion). These question-answer sets were then evaluated by the rating group. All answers were scored from 1 to 9. The comments of the rating group were incorporated by the steering group and the consensus was submitted to the rating group a second time. Once a general consensus was reached between the steering and rating groups, the question-answer sets were submitted to the peer review group. A final combined meeting of all the members of the consensus was held to ratify the document. RESULTS: The literature review for the diagnosis and preoperative planning of ACL revision revealed a rather low scientific quality. None of the 18 questions was graded A and six received a grade B. The mean rating of all the questions by the rating group was 8.4 ± 0.3. The questions and recommendations are listed below. CONCLUSION: ACL revision surgery is a widely debated subject with many different opinions and techniques. The literature reveals a poor level of standardisation. Therefore, this international consensus project is of great importance. LEVEL OF EVIDENCE: II.

Management of anterior cruciate ligament revision in adults: the 2022 ESSKA consensus: part II-surgical strategy.

PURPOSE: The aim of this ESSKA consensus is to give recommendations based on scientific evidence and expert opinion to improve the diagnosis, preoperative planning, indication and surgical strategy in Anterior Cruciate Ligament revision. METHODS: Part 2, presented herein, followed exactly the same methodology as Part 1: the so-called ESSKA formal consensus derived from the Delphi method. Eighteen questions were ultimately asked. The quality of the answers received the following grades of recommendation: Grade A (high level scientific support), Grade B (scientific presumption), Grade C (low level scientific support) or Grade D (expert opinion). All answers were scored from 1 to 9 by the raters. Once a general consensus had been reached between the steering and rating groups, the question-answer sets were submitted to the peer-review group. A final combined meeting of all the members of the consensus was then held to ratify the document. RESULTS: The review of the literature revealed a rather low scientific quality of studies examining the surgical strategy in cases of ACL reconstruction failure. Of the 18 questions, only 1 received a Grade A rating; 5, a Grade B rating; and 9, grades of C or D. The three remaining complex questions received further evaluations for each portion of the question and were looked at in more detail for the following grades: B and D; A, C and D; or A, B, C and D. The mean rating of all questions by the rating group was 8.0 + - 1.1. The questions and recommendations are listed in the article. CONCLUSION: ACL revision surgery, especially the surgical strategy, is a widely debated subject with many different opinions and techniques. The literature reveals a poor level of standardization. Therefore, this international European consensus project is of great importance and clinical relevance for guiding the management of ACL revision in adults. LEVEL OF EVIDENCE: Level II.

Management of anterior cruciate ligament revision in adults: the 2022 ESSKA consensus part III-indications for different clinical scenarios using the RAND/UCLA appropriateness method.

PURPOSE: The aim of the ESSKA 2022 consensus Part III was to develop patient-focused, contemporary, evidence-based, guidelines on the indications for revision anterior cruciate ligament surgery (ACLRev). METHODS: The RAND/UCLA Appropriateness Method (RAM) was used to provide recommendations on the appropriateness of surgical treatment versus conservative treatment in different clinical scenarios based on current scientific evidence in conjunction with expert opinion. A core panel defined the clinical scenarios with a moderator and then guided a panel of 17 voting experts through the RAM tasks. Through a two-step voting process, the panel established a consensus as to the appropriateness of ACLRev for each scenario based on a nine-point Likert scale (in which a score in the range 1-3 was considered 'inappropriate', 4-6 'uncertain', and 7-9 'appropriate'). RESULTS: The criteria used to define the scenarios were: age (18-35 years vs 36-50 years vs 51-60 years), sports activity and expectation (Tegner 0-3 vs 4-6 vs 7-10), instability symptoms (yes vs no), meniscus status (functional vs repairable vs non-functional meniscus), and osteoarthritis (OA) (Kellgren-Lawrence [KL] grade 0-I-II vs grade III). Based on these variables, a set of 108 clinical scenarios was developed. ACLRev was considered appropriate in 58%, inappropriate in 12% (meaning conservative treatment is indicated), and uncertain in 30%. Experts considered ACLRev appropriate for patients with instability symptoms, aged ≤ 50 years, regardless of sports activity level, meniscus status, and OA grade. Results were much more controversial in patients without instability symptoms, while higher inappropriateness was related to scenarios with older age (51-60 years), low sporting expectation, non-functional meniscus, and knee OA (KL III). CONCLUSION: This expert consensus establishes guidelines as to the appropriateness of ACLRev based on defined criteria and provides a useful reference for clinical practice in determining treatment indications. LEVEL OF EVIDENCE: II.

Subacromial impingement syndrome: association of multiple magnetic resonance imaging parameters with shoulder function and pain.

INTRODUCTION: Shoulder pain is one of the most common complaints in orthopaedics. This study focusses on the relationship between shoulder function in subacromial impingement syndrome and imaging criteria in magnetic resonance imaging (MRI). MATERIALS AND METHODS: This prospective clinical trial included 69 patients treated for subacromial impingement syndrome. Shoulder function (Constant Score, range of abduction, abduction force) and pain were correlated with the following MRI parameters: tendinosis of the rotator cuff, "halo-sign" around the biceps tendon, subacromial distance, critical shoulder angle, size of subacromial osteophytic spurs and maximum width of subacromial and subdeltoid bursa. Statistical analyses included Pearson's and Spearman's coefficients of correlation, multiple regression analysis and Student's t-test. RESULTS: The Constant Score was correlated positively with the critical shoulder angle (r = 0.313; p = 0.009) and inversely with a "halo-sign" around the biceps tendon (rho = -0.384; p = 0.001). There was no significant correlation between spur size and shoulder function, but the size of the subacromial and subdeltoid bursae was positively correlated with the subacromial spur's size (subacromial bursa: coronal plane: r = 0.327; p = 0.006; sagittal view: r = 0.305; p = 0.011; subdeltoid bursa coronal view: r = 0.333 p = 0.005). The width of the subdeltoid bursa in coronal plane was positively correlated with shoulder pain (r = 0.248; p = 0.004) and negatively with the range of abduction (r = -0.270; p = 0.025), as well as the mean (r = -0.332; p = 0.005) and maximum (r = -0.334; p = 0.005) abduction force. CONCLUSIONS: Shoulder function and pain in subacromial impingement are best predicted by the width of the subdeltoid bursa measured in the coronal MRI plane as an indicator of bursitis as well as the presence of a "halo-sign" around the biceps tendon indicating glenohumeral joint effusion. Presence of a subacromial spur could lead to subacromial and subdeltoid bursitis, which impairs shoulder function. Shoulder function seems not to be compromised by the presence of a subacromial spur in absence of bursitis. This study was registered at the German Clinical Trials Register on 08 February 2013 (ID: DRKS00011548).