Diagnostic Accuracy of Candidate Magnetic Resonance Imaging Knee Osteoarthritis Definitions Versus Radiograph in an Acute Anterior Cruciate Ligament Injury Cohort.

OBJECTIVE: We tested the diagnostic accuracy of previously proposed magnetic resonance imaging (MRI) osteoarthritis (OA) definitions in a cohort after acute anterior cruciate ligament (ACL) injury. METHODS: We studied participants with posteroanterior and lateral knee radiographs and MRI 5 years after ACL injury, scored using the Anterior Cruciate Ligament Osteoarthritis Score. Radiographic OA (ROA) was defined using Osteoarthritis Research Society International scoring of osteophytes and joint space narrowing considering medial/lateral tibiofemoral and patellofemoral compartments. We tested three candidate MRI OA definitions that performed well in an older adult cohort. "Multicenter Osteoarthritis Study (MOST) simple" required cartilage score ≥2 (range 0-6) and osteophyte score ≥2 (0-7); "MOST optional" included cartilage score ≥2, osteophyte score ≥2, and either bone marrow lesions (BMLs) ≥1 (0-3) or synovitis ≥2 (0-3). The third, a Delphi panel definition, included nonzero scores for cartilage, osteophyte, BMLs, meniscus, and other structures. We calculated sensitivity and specificity with 95% confidence intervals (95% CIs) for each MRI definition versus ROA. RESULTS: We included 113 participants (mean age 26 years, 26% female). At 5 years, 29 participants (26%) had ROA. "MOST simple" had a sensitivity of 52% (95% CI 33%-71%), and specificity of 76% (95% CI 66%-85%). Sensitivity and specificities for "MOST optional" were 28% (95% CI 29%-67%) and 83% (95% CI 74%-91%), respectively. The Delphi panel definition had a sensitivity of 48% (95% CI 29%-67%) and specificity of 77% (95% CI 67%-86%). CONCLUSION: Simple MRI-based OA definitions requiring at least cartilage damage and an osteophyte have low sensitivity and high specificity in young persons after knee injury.

Clinical, patient-reported, radiographic and magnetic resonance imaging findings 11 years after acute posterior cruciate ligament injury treated non-surgically.

BACKGROUND: Long-term consequences of posterior cruciate ligament (PCL) injury such as persistent posterior tibial translation and risk of osteoarthritis development are unclear. Additionally, little data is available describing the natural history of structural morphology of the ruptured PCL. The purpose of the study was to determine the long-term outcome after non-operatively treated PCL injury. METHODS: Over 6-years, all acute knee injuries were documented by subacute MRI (median 8 days [5-15, 25th - 75th percentile] from injury to MRI). Twenty-six patients with acute PCL injury were identified of whom 18 (69%) participated in the long-term follow-up after 11 years. Follow-up included radiographic posterior tibial translation (RPTT) determined using the Puddu axial radiograph. weight-bearing knee radiographs, MRI and KOOS (Knee injury and Osteoarthritis Outcome Score). RESULTS: On subacute MRI, 11 knees displayed total and 7 partial ruptures. At 11 (SD 1.9) years, the median RPTT was 3.7 mm (1.5-6.3, 25th - 75th percentile). Seven knees displayed radiographic osteoarthritis approximating Kellgren-Lawrence grade ≥ 2. All follow-up MRIs displayed continuity of the PCL. Patients with more severe RPTT (> 3.7 mm), had worse scores in the KOOS subscales for symptoms (mean difference 14.5, 95% CI 7-22), sport/recreation (30, 95% CI 0-65) and quality of life (25, 95% CI 13-57) than those with less severe RPTT (≤ 3.7 mm). This was also the case for the KOOS4 (22, 95% CI 9-34). CONCLUSION: Acute PCL injuries treated non-surgically display a high degree of PCL continuity on MR images 11 years after injury. However, there is a large variation of posterior tibial translation with higher values being associated with poorer patient-reported outcomes.

Factors associated with healing failure after early repair of acute, trauma-related rotator cuff tears.

BACKGROUND: Healing failure after rotator cuff repair is a challenging problem. Acute, trauma-related tears are considered a separate entity and are often treated surgically. The aim of this study was to identify factors associated with healing failure in previously asymptomatic patients with trauma-related rotator cuff tears treated with early arthroscopic repair. METHODS: This study included 62 consecutively recruited patients (23% women; median age, 61 years; age range, 42-75 years) with acute symptoms in a previously asymptomatic shoulder and a magnetic resonance imaging-verified full-thickness rotator cuff tear after shoulder trauma. All patients were offered, and underwent, early arthroscopic repair, during which a biopsy specimen was harvested from the supraspinatus tendon and analyzed for signs of degeneration. Of the patients, 57 (92%) completed 1-year follow-up and underwent assessment of repair integrity on magnetic resonance images according to the Sugaya classification. Risk factors for healing failure were investigated using a causal-relation diagram where age, body mass index, tendon degeneration (Bonar score), diabetes mellitus, fatty infiltration (FI), sex, smoking, tear location regarding integrity of the rotator cable, and tear size (number of ruptured tendons and tendon retraction) were included and analyzed. RESULTS: Healing failure at 1 year was identified in 37% of patients (n = 21). A high degree of FI of the supraspinatus muscle (P = .01), a tear location including disruption of rotator cable integrity (P = .01), and old age (P = .03) were associated with healing failure. Tendon degeneration as determined by histopathology was not associated with healing failure at 1-year follow-up (P = .63). CONCLUSION: Older age, increased FI of the supraspinatus muscle, and a tear including disruption of the rotator cable increased the risk of healing failure after early arthroscopic repair in patients with trauma-related full-thickness rotator cuff tears.

Incidence and concomitant chondral injuries in a consecutive cohort of primary traumatic patellar dislocations examined with sub-acute MRI.

PURPOSE: To present age- and sex-specific cumulative annual incidences of primary traumatic lateral patellar dislocation (LPD) and to detail patient characteristics and concomitant chondral injuries including osteochondral fractures, as visualized on magnetic resonance imaging (MRI), in a large consecutive cohort of knee-injured individuals. METHODS: Data on primary traumatic lateral patellar dislocations were collected from a large consecutive cohort of knee injuries examined with sub-acute MRI in a single centre with a well-defined catchment area. Annual incidences for different age-groups in relation to gender were calculated together with the risk of concomitant chondral and osteochondral injury, during sports and in general. RESULTS: A total of 184 primary patellar dislocations were identified in the cohort of 1145 acute knee injuries (n=175) and surgical records (n=9). Knee MRI was performed within a median of six days of injury. Median age of patients with primary LPD was 16 years (interquartile range, 14-21; range, 9-47) and 41% were females. Males were significantly older than females at the time of injury (median age 17 vs. 15, P = 0.021) and sustained their primary LPD during sports more often than females (65 vs. 40%, P < 0.001). Primary LPD occurred most frequently at the age of 13 to 15 years where the annual incidence was 125 (95% CI, 96-160) per 100,000 persons. The overall annual incidence of primary LPD was 14 (95% CI, 12-16) per 100,000 persons, with a predominance of males versus females (17 vs. 11, P = 0.01). Concomitant lesions to joint surfaces were displayed on MRI or during surgery in 75 (43%) knees. Osteochondral fractures were seen in 32 knees (18%). We found no statistically significant difference in the risk of osteochondral fracture between those injured during sports or during leisure activity (14 vs. 24%, P = 0.08). CONCLUSIONS: The annual incidence of first-time patellar dislocation was found to be 14 per 100,000 individuals with the highest incidence found among those aged 13-15 years. Primary LPD was more common among males and was sustained during sports activity in 55% of the cases. Associated injuries to the chondral surfaces should be expected in 43% of knees with primary LPD where 18% represent osteochondral fractures.

Evidence of ACL healing on MRI following ACL rupture treated with rehabilitation alone may be associated with better patient-reported outcomes: a secondary analysis from the KANON trial.

OBJECTIVES: Evaluate the natural course of anterior cruciate ligament (ACL) healing on MRI within 5 years of acute ACL rupture and compare 2-year and 5-year outcomes based on healing status and treatment group. METHODS: Secondary analysis of 120 Knee Anterior Cruciate Ligament Nonsurgical vs Surgical Treatment (KANON) trial participants randomised to rehabilitation and optional delayed ACL reconstruction (ACLR) or early ACLR and rehabilitation. ACL continuity on MRI (Anterior Cruciate Ligament OsteoArthritis Score 0-2) was considered evidence of ACL healing. Outcomes included Knee Injury and Osteoarthritis Outcome Score (KOOS), KOOS patient acceptable symptomatic state (PASS) and treatment failure criteria. Linear mixed models were used to estimate adjusted mean differences (95% CIs) in patient-reported sport and recreational function (KOOS-Sport/Rec) and quality of life (KOOS-QOL) at 2 and 5 years, between participants with MRI evidence of ACL healing and those who had (1) no evidence of ACL healing, (2) delayed ACLR or (3) early ACLR. RESULTS: MRI evidence of ACL healing at 2-year follow-up was observed in 16 of 54 (30%, 95% CI 19 to 43%) participants randomised to optional delayed ACLR. Excluding participants who had delayed ACLR, 16 of 30 (53%, 36-70%) participants managed with rehabilitation-alone displayed MRI evidence of ACL healing. Two-year outcomes were better in the healed ACL group (n=16) compared with the non-healed (n=14) (mean difference (95% CI) KOOS-Sport/Rec: 25.1 (8.6-41.5); KOOS-QOL: 27.5 (13.2-41.8)), delayed ACLR (n=24) (KOOS-Sport/Rec: 24.9 (10.2-39.6); KOOS-QOL: 18.1 (5.4-30.8)) and early ACLR (n=62) (KOOS-Sport/Rec: 17.4 (4.1-30.7); KOOS-QOL: 11.4 (0.0-22.9)) groups. Five-year KOOS-QOL was better in the healed versus non-healed group (25.3 (9.4-41.2)). Of participants with MRI evidence of ACL healing, 63-94% met the PASS criteria for each KOOS subscale, compared with 29-61% in the non-healed or reconstructed groups. CONCLUSIONS: MRI appearance of ACL healing after ACL rupture occurred in one in three adults randomised to initial rehabilitation and one in two who did not cross-over to delayed ACLR and was associated with favourable outcomes. The potential for spontaneous healing of the ACL to facilitate better clinical outcomes may be greater than previously considered. TRIAL REGISTRATION NUMBER: ISRCTN84752559.

Treatment for Acute Anterior Cruciate Ligament Tear in Young Active Adults.

BACKGROUND: Anterior cruciate ligament (ACL) injury of the knee is common in young active adults and often has severe and sometimes lifelong consequences. The clinical management of this injury remains debated. A prior trial of early versus delayed optional ACL repair showed no differences in outcomes at 2 years. METHODS: We present the 11-year follow-up of a randomized clinical trial involving 121 young active adults (mean age 26yo, 74% male) with an acute sports-related ACL tear. We compared patient-reported and radiographic outcomes between those randomized to receive early ACL reconstruction (ACLR) followed by exercise therapy (N=62) and those treated with early exercise therapy plus optional delayed ACLR (N=59). The primary end point at 11 years was change from baseline in the mean of four subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS) ­ pain, symptoms, function in sports and recreation, and knee-related quality of life (KOOS4; range of scores, 0 [worst] to 100 [best]; minimal important change=9). RESULTS: In all, 88% of the cohort followed up at 11 years (53/62 in the early vs. 54/59 in the optional late ACL repair groups), and 52% of those assigned to optional delayed ACLR underwent ACLR. Mean improvement in KOOS4 from baseline to 11 years was 46 points for those assigned to early ACLR plus exercise therapy and 45 points for those assigned to exercise therapy plus optional delayed ACLR (between-group difference, 1.6 points; 95% confidence interval [CI], −8.8 to 5.6; P=0.67 after adjustment for baseline score, full analysis set). About two thirds of the full cohort reported meeting the case definition for a "patient-acceptable symptom state" (KOOS4 patient-acceptable symptom state threshold value=79), whereas 44% had developed radiographic osteoarthritis of their injured knee. Mean summed incident radiographic osteoarthritis feature scores, scores range from 0 to 30 where higher scores indicate more severe joint damage, were 2.4 for the group assigned to early ACLR and 1.0 for the group assigned to exercise therapy plus optional delayed ACLR (mean difference, 1.0; 95% CI, 0.1 to 1.9). CONCLUSIONS: At 11-year follow-up, among young active adults with acute ACL tears assigned to early ACLR plus exercise versus initial exercise therapy with the option of delayed ACLR, there were no differences in patient-reported outcomes. (Funded by the Swedish Research Council; ISRCTN number, ISRCTN84752559.)

The challenge of recruiting multimorbid older patients identified in a hospital database to a randomised controlled trial.

BACKGROUND: Research involving multimorbid older patients is gaining momentum. However, little is known about how to plan a randomised controlled trial (RCT) involving this group of patients. An evidence-based approach to the challenges of a recruitment process could guide researchers and help prevent underpowered trials. AIM: To define the number of multimorbid older patients that need to be identified and the number of eligible patients that need to be invited to achieve the desired recruitment number to a RCT. METHOD: We used recruitment data from the GerMoT trial, a RCT comparing proactive outpatient care based on Comprehensive Geriatric Assessment with usual care. Multimorbid older patients with high healthcare utilisation were recruited to the trial. RESULTS: Of the 1212 patients identified in a database as meeting the inclusion criteria 838 (70%) could be invited to participate in the trial. The rest could not be invited for a variety of reasons; 162 had moved out of area or into nursing homes and 86 had died before they could be contacted. 113 could not be reached. 450 (54%) of the invited patients agreed to participate. CONCLUSIONS: In our study, we have shown that it is possible to achieve a good consent rate despite older participants with multimorbidity. This can be used when planning an RCT for this patient group, who are often excluded from clinical trials. Our results are specific to a context that provides similar abilities to identify and recruit patients as can be seen in Sweden.

No differences in histopathological degenerative changes found in acute, trauma-related rotator cuff tears compared with chronic, nontraumatic tears.

PURPOSE: Acute trauma-related rotator cuff tears are believed to have better healing potential than chronic tears due to less degenerative changes of the tendons. However, the histopathological condition of tendons from trauma-related tears is not well investigated. The purpose of this study was to explore specific histopathological features in tendons from acute trauma-related full-thickness rotator cuff tears and to compare them to findings in tendons from nontraumatic, chronic tears. METHODS: In a prospective cohort study, 62 previously asymptomatic patients [14 women, median age 61 years (range 42-75)] with trauma-related full-thickness rotator cuff tears were consecutively included. Arthroscopic repair was performed within 30 (median, IQR 25-37) days after the injury. During surgery, tissue biopsies were harvested from the supraspinatus tendons in 53 (86%) of the patients. In addition, similar biopsies were harvested from 10 patients undergoing surgery for chronic tears without history of trauma. All tissue samples were examined by a well-experienced pathologist under light microscope. Tendon degeneration was determined using the Bonar score whereas immunostaining was used for proliferation (Ki67), inflammation (CD45), apoptosis (p53) and haemosiderin staining to study traces of bleeding. RESULTS: The median (IQR) Bonar score for the acute trauma-related biopsies was 10.5 (7.5-14.5) compared to 11 (5-12.8) for the control group with no statistically significant difference between the groups. No statistically significant between-group difference was found for the inflammatory index whereas tendons from patients with trauma-related full-thickness rotator cuff tears had statistically significantly higher apoptosis [3.1 (0.5-8.9) vs. 0.1 (0-1.5), p = 0.003] and proliferation [4.0 (1.8-6.9) vs. 0.4 (0-2.0), p = 0.001) indices than those undergoing surgery for chronic tears. Positive haemosiderin staining was found in 34% of tissue samples from patients with trauma-related tears compared to 10% in the control group (n.s). CONCLUSION: This study suggests that there is no difference with regard to degenerative changes between supraspinatus tendons harvested from patients with acute, trauma-related rotator cuff tears and patients with nontraumatic, chronic tears. LEVEL OF EVIDENCE: II.

Agreement Between Clinical Examination and Magnetic Resonance Imaging in Acute Knee Trauma With Hemarthrosis.

OBJECTIVE: Hemarthrosis after knee trauma often indicates serious joint injury. Few studies have evaluated agreement between clinical examination and findings from magnetic resonance imaging (MRI). We aimed to describe the agreement between acute clinical examination and subacute MRI findings after acute knee trauma with hemarthrosis and the importance of the subspecialty of the examiner. DESIGN: Longitudinal cohort study. Agreement with MRI findings was evaluated by logistic regression. SETTING: Helsingborg hospital. PATIENTS: Thousand one hundred forty-five consecutive patients with hemarthrosis after knee trauma. INTERVENTIONS: Clinical examination and MRI. MAIN OUTCOME MEASURES: agreement between clinical examination and findings from MRI. We considered the radiologist's report as the gold standard. RESULTS: Median time (25th, 75th percentile) from injury to clinical examination was 2 (1, 7) days, and from injury to imaging was 8 (5, 15) days. The overall sensitivity and specificity of clinical examination versus MRI for major ligament injury or lateral patella dislocation (LPD) were 70% [95% confidence interval 67-73) and 66% (61-72), respectively. Orthopedic subspecialist knee had the highest agreement with anterior cruciate ligament rupture (adjusted odds ratios were 1.7 (95% confidence interval 1.2-2.3), 1.9 (1.2-3.0) and 5.9 (3.7-9.5) for orthopedic trainees, orthopedic subspecialists other, and orthopedic subspecialist knee, respectively]. For other ligament injuries and LPD, we did not find statistically significant differences. CONCLUSIONS: Clinical diagnosis after acute knee injury is relatively unreliable versus MRI findings even when performed by orthopedic specialists. However, the agreement is improved when the examination is performed by an orthopedic knee subspecialist.

An Anterior Cruciate Ligament Rupture Increases Levels of Urine N-terminal Cross-linked Telopeptide of Type I Collagen, Urine C-terminal Cross-linked Telopeptide of Type II Collagen, Serum Aggrecan ARGS Neoepitope, and Serum Tumor Necrosis Factor-α.

BACKGROUND: An anterior cruciate ligament (ACL) rupture results in an increased risk of developing knee osteoarthritis (OA) at an early age. Before clinical signs become apparent, the OA process has already been initiated. Therefore, it is important to look at the cascade of changes, such as the activity of cytokines and proteases, which might be associated with the later development of OA. PURPOSE: To compare biomarker levels in patients with a recent ACL rupture with those in controls with a healthy knee and to monitor biomarker levels over 2 years after an ACL rupture. STUDY DESIGN: Descriptive laboratory study. METHODS: Patients were enrolled after an ACL tear was identified. Serum and urine samples were collected at the time of enrollment in the study (3-25 weeks after the injury) and then at 14 and 27 months after the injury between January 2009 and November 2010. Reference samples were obtained from participants with healthy knees. The following biomarkers were measured with immunological assays: aggrecan ARGS neoepitope (ARGS-aggrecan), tumor necrosis factor-α (TNF-α), interferon-γ, interleukin (IL)-8, IL-10, IL-13, N-terminal cross-linked telopeptide of type I collagen (NTX-I), and C-terminal cross-linked telopeptide of type II collagen (CTX-II). RESULTS: Samples were collected from 152 patients with an acute ACL rupture, who had a median age of 25 years (interquartile range [IQR], 21-32 years). There were 62 urine reference samples (median age, 25 years [IQR, 22-36 years]) and 26 serum reference samples (median age, 35 years [IQR, 24-39 years]). At a median of 11 weeks (IQR, 7-17 weeks) after trauma, serum levels of both ARGS-aggrecan and TNF-α were elevated 1.5-fold (P < .001) compared with reference samples and showed a time-dependent decrease during follow-up. Urine NTX-I and CTX-II concentrations were elevated in an early phase after trauma (1.3-fold [P < .001] and 3.7-fold [P < .001], respectively) compared with reference samples, and CTX-II levels remained elevated compared with reference samples at 2-year follow-up. Strong correlations were found between serum ARGS-aggrecan, urinary NTX-I, and urinary CTX-II (rs = 0.57-0.68). CONCLUSION: In the first few months after an ACL injury, there was a measurable increase in serum levels of ARGS-aggrecan and TNF-α as well as urine levels of NTX-I and CTX-II. These markers remained high compared with those of controls with healthy knees at 2-year follow-up.

Development of MRI-defined Structural Tissue Damage after Anterior Cruciate Ligament Injury over 5 Years: The KANON Study.

Background MRI is used to evaluate structural joint changes after anterior cruciate ligament (ACL) injury, but no long-term data are available for comparing different treatment approaches. Purpose To describe structural joint damage with MRI over a 5-year period in the Knee Anterior Cruciate Ligament, Nonsurgical versus Surgical Treatment (KANON) study and to compare frequencies of such tissue damage for a nonsurgical versus a surgical treatment strategy. Materials and Methods In this secondary analysis of a prospective trial (ISRCTN 84752559), 119 participants with an acute ACL injury were evaluated. Participants were enrolled from 2002 through 2006, the 2-year follow-up started in 2008, and the 5-year follow-up started in 2011. A 1.5-T MRI examination was performed at baseline and at 2- and 5-year follow-up. MRI scans were read according to a validated scoring instrument. Kruskal-Wallis tests were used to assess whether the frequencies of structural damage differed between the three as-treated groups. Results Of 119 participants (mean age, 26 years ± 5 [standard deviation]), 91 men were evaluated. At 2- and 5-year follow-up, respectively, 13% (15 of 117) and 13% (15 of 115) of knees showed incident cartilage damage in the medial tibiofemoral joint, 11% (13 of 117) and 17% (20 of 115) of knees showed incident cartilage damage in the lateral tibiofemoral joint, and 4% (five of 117) and 8% (nine of 115) of knees showed incident cartilage damage in the patellofemoral joint. Osteophyte development was seen in 23% (27 of 117) and 29% (33 of 115) of knees in the medial tibiofemoral joint, in 36% (42 of 117) and 43% (49 of 115) of knees in the lateral tibiofemoral joint, and in 35% (41 of 117) and 37% (42 of 115) of knees in the patellofemoral joint. No major differences between the groups were found for incident or worsening cartilage damage, bone marrow lesions, and osteophytes at 2 or 5 years. The rehabilitation-alone group showed less Hoffa-synovitis at 2 (P = .02) and 5 (P = .008) years. Conclusion Young adults with anterior cruciate ligament injury showed no major difference in frequency of structural tissue damage on MRI scans at 2 and 5 years regardless of treatment. However, the rehabilitation-alone group had less inflammation at 2 and 5 years. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Andreisek in this issue.

High genetic contribution to anterior cruciate ligament rupture: Heritability ~69.

OBJECTIVES: We aimed to determine the lifetime genetic risk for anterior cruciate ligament (ACL) rupture. METHODS: We used a twin study approach, linking the Swedish Twin Register with national healthcare data to form a 30 year, population wide, longitudinal twin cohort. We studied ACL rupture in this cohort of 88 414 identical and fraternal twins, aged ≥17 years, to determine the familial risk and heritability of ACL rupture. RESULTS: The incidence rate of ACL rupture was 70 (95% CI 66 to 74) per 100 000 person years. The familial risk, which is the excess risk ratio (RR) of the second twin having ACL rupture given that the first twin has had such a rupture, was higher in identical twin pairs (RR=8.6, 95% CI 6.2 to 11.0) than in fraternal twin pairs (RR=1.9, 95% CI 0.9 to 3.0). The overall heritability of ACL rupture was high, 69% (95% CI 47 to 91), increasing from 60% at age 17 years to 80% at age 60 years. Women and men had similar familial risk and heritability of ACL rupture. CONCLUSION: The genetic contribution to ACL rupture of ~69% is high and suggests strong familial clustering. If clinicians recognise the high genetic risk of such injury, they may be better able to counsel athletes whose near relatives have had ACL rupture.

Does early anterior cruciate ligament reconstruction prevent development of meniscal damage? Results from a secondary analysis of a randomised controlled trial.

OBJECTIVES: To determine development of new and worsening meniscal damage over 5 years after acute anterior cruciate ligament (ACL) injury comparing rehabilitation plus early ACL reconstruction ('early-ACLR') versus rehabilitation with optional delayed ACL reconstruction ('optional-delayed-ACLR'). METHODS: We used knee MRIs from the only randomised controlled trial in the field including 121 young adults. One musculoskeletal radiologist read baseline and 5-year follow-up images using the Anterior Cruciate Ligament Osteoarthritis Score (ACLOAS). We defined development (ie, new and worsening) of meniscal damage both dichotomously and as a sum score representing severity (based on the reclassified ACLOAS meniscus grades). In the full analysis set, we analysed development of meniscal damage (yes/no) with logistic regression and severity with zero-inflated Poisson regression and adjusted for age, sex and baseline meniscal damage. RESULTS: Over 5 years, new or worsening meniscal damage developed in 45% of subjects with early-ACLR and in 53% of subjects with optional-delayed-ACLR. The relative risk for development of meniscal damage on knee level was 1.3 (95% CI 0.9 to 1.9) in optional-delayed-ACLR versus early-ACLR. For medial and lateral meniscal damage, respectively, the relative risks were 2.1 (95% CI 1.1 to 3.9) and 1.0 (95% CI 0.6 to 1.5). The mean severity score was 1.5 higher (more severe damage) on knee level in optional-delayed-ACLR versus early-ACLR (95% CI 1.1 to 1.9) among those with meniscal damage at 5 years. For medial and lateral meniscal damage, respectively, the corresponding scores were 1.7 (95% CI 1.2 to 2.5) and 1.1 (95% CI 0.8 to 1.4). CONCLUSION: A strategy of early-ACLR may reduce development of medial meniscal damage following acute ACL injury. For the lateral meniscus, ACLR seems neither to be protective nor to increase the risk of damage. TRIAL REGISTRATION NUMBER: ISRCTN 84752559.

Risk of knee osteoarthritis after different types of knee injuries in young adults: a population-based cohort study.

OBJECTIVES: To estimate the risk of clinically diagnosed knee osteoarthritis (OA) after different types of knee injuries in young adults. METHODS: In a longitudinal cohort study based on population-based healthcare data from Skåne, Sweden, we included all persons aged 25-34 years in 1998-2007 (n=149 288) with and without diagnoses of knee injuries according to International Classification of Diseases (ICD)-10. We estimated the HR of future diagnosed knee OA in injured and uninjured persons using Cox regression, adjusted for potential confounders. We also explored the impact of type of injury (contusion, fracture, dislocation, meniscal tear, cartilage tear/other injury, collateral ligament tear, cruciate ligament tear and injury to multiple structures) on diagnosed knee OA risk. RESULTS: We identified 5247 persons (mean (SD) age 29.4 (2.9) years, 67% men) with a knee injury and 142 825 persons (mean (SD) age 30.2 (3.0) years, 45% men) without. We found an adjusted HR of 5.7 (95% CI 5.0 to 6.6) for diagnosed knee OA in injured compared with uninjured persons during the first 11 years of follow-up and 3.4 (95% CI 2.9 to 4.0) during the following 8 years. The corresponding risk difference (RD) after 19 years of follow-up was 8.1% (95% CI 6.7% to 9.4%). Cruciate ligament injury, meniscal tear and fracture of the tibia plateau/patella were associated with greatest increase in risk (RD of 19.6% (95% CI 13.2% to 25.9%), 10.5% (95% CI 6.4% to 14.7%) and 6.6% (95% CI 1.1% to 12.2%), respectively). CONCLUSION: In young adults, knee injury increases the risk of future diagnosed knee OA about sixfold with highest risks found after cruciate ligament injury, meniscal tear and intra-articular fracture.

It is good to feel better, but better to feel good: whether a patient finds treatment 'successful' or not depends on the questions researchers ask.

INTRODUCTION: In sports physiotherapy, medicine and orthopaedic randomised controlled trials (RCT), the investigators (and readers) focus on the difference between groups in change scores from baseline to follow-up. Mean score changes are difficult to interpret ('is an improvement of 20 units good?'), and follow-up scores may be more meaningful. We investigated how applying three different responder criteria to change and follow-up scores would affect the 'outcome' of RCTs. Responder criteria refers to participants' perceptions of how the intervention affected them. METHODS: We applied three different criteria-minimal important change (MIC), patient acceptable symptom state (PASS) and treatment failure (TF)-to the aggregate Knee injury and Osteoarthritis Outcome Score (KOOS4) and the five KOOS subscales, the primary and secondary outcomes of the KANON trial (ISRCTN84752559). This trial included young active adults with an acute ACL injury and compared two treatment strategies: exercise therapy plus early reconstructive surgery, and exercise therapy plus delayed reconstructive surgery, if needed. RESULTS: MIC: At 2 years, more than 90% in the two treatment arms reported themselves to be minimally but importantly improved for the primary outcome KOOS4. PASS: About 50% of participants in both treatment arms reported their KOOS4 follow-up scores to be satisfactory. TF: Almost 10% of participants in both treatment arms found their outcomes so unsatisfactory that they thought their treatment had failed. There were no statistically significant or meaningful differences between treatment arms using these criteria. CONCLUSION: We applied change criteria as well as cross-sectional follow-up criteria to interpret trial outcomes with more clinical focus. We suggest researchers apply MIC, PASS and TF thresholds to enhance interpretation of KOOS and other patient-reported scores. The findings from this study can improve shared decision-making processes for people with an acute ACL injury.

Loss of patellofemoral cartilage thickness over 5 years following ACL injury depends on the initial treatment strategy: results from the KANON trial.

OBJECTIVES: To evaluate changes in patellofemoral cartilage thickness over 5 years after anterior cruciate ligament (ACL) injury and to determine the impact of treatment strategy. METHODS: 121 adults (ages 18-35 years, 26% women) had an ACL injury and participated in the KANON randomised controlled trial. Of those, 117 had available MRIs at baseline (<4 weeks post-ACL rupture) and at least one follow-up measurement (2, 5 years). Patellofemoral cartilage thickness was analysed by manual segmentation (blinded to acquisition order). Patellar, trochlear and total patellofemoral cartilage thickness changes were compared between as-randomised (rehabilitation+early ACL reconstruction (ACLR) (n=59) vs rehabilitation+optional delayed ACLR (n=58)) and as-treated groups (rehabilitation+early ACLR (n=59) vs rehabilitation +delayed ACLR (n=29) vs rehabilitation alone (n=29)). RESULTS: Patellofemoral cartilage thickness decreased -58 µm (95% CI -104 to -11 µm) over 5 years post-ACL rupture, with the greatest loss observed in trochlea during the first 2 years. Participants randomised to rehabilitation+early ACLR had significantly greater loss of patellar cartilage thickness compared with participants randomised to rehabilitation+optional delayed ACLR over the first 2 years (-25 µm (-52, 1 µm) vs +14 µm (-6 to 34 µm), p=0.02) as well as over 5 years (-36 µm (-78 to 5 µm) vs +18 µm (-7, 42 µm), p=0.02). There were no statistically significant differences in patellofemoral cartilage thickness changes between as-treated groups. CONCLUSION: Patellofemoral (particularly trochlear) cartilage thickness loss was observed in young adults following acute ACL rupture. Early ACLR was associated with greater patellofemoral (particularly patellar) cartilage thickness loss over 5 years compared with optional delayed ACLR, indicating that early surgical intervention may be associated with greater short-term structural patellofemoral cartilage deterioration compared with optional delayed surgery. TRIAL REGISTRATION NUMBER: ISRCTN84752559; Post-results.

Molecular and Structural Biomarkers of Inflammation at Two Years After Acute Anterior Cruciate Ligament Injury Do Not Predict Structural Knee Osteoarthritis at Five Years.

OBJECTIVE: To determine the role of inflammatory biomarkers at 2 years post-anterior cruciate ligament (ACL) injury to predict radiographic knee osteoarthritis (OA) and magnetic resonance imaging (MRI)-defined knee OA at 5 years postinjury, with a secondary aim of estimating the concordance of inflammatory biomarkers assessed by MRI and synovial fluid (SF) analysis. METHODS: We studied 113 patients with acute ACL injury. Knee scans using 1.5T MRIs were read for Hoffa- and effusion-synovitis. Biomarkers of inflammation that we assessed included interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor, and interferon-É£ in serum and SF, and IL-12p70 in serum. We defined the outcome as radiographic knee OA (ROA) or MRI-defined OA (MROA) at 5 years. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were evaluated in models that included MRI features only (model 1), inflammation biomarkers only (serum [model 2a] or SF [model 2b]), both MRI features and serum biomarkers (model 3a), or both MRI features and SF (model 3b) biomarkers. Linear regression analysis was used to evaluate the association between MRI features and SF biomarkers. RESULTS: At 5 years postinjury, ROA was present in 26% of the injured knees, and MROA was present in 32%. The AUCs for ROA in each model were 0.44 (95% confidence interval [95% CI] 0.42, 0.47) for model 1, 0.62 (95% CI 0.59, 0.65) for model 2a, 0.53 (95% CI 0.50, 0.56) for model 2b, 0.58 (95% CI 0.55, 0.61) for model 3a, and 0.50 (95% CI 0.46, 0.53) for model 3b. The AUCs for MROA in each model were 0.67 (95% CI 0.64, 0.70) for model 1, 0.49 (95% CI 0.47, 0.52) for model 2a, 0.56 (95% CI 0.52, 0.59) for model 2b, 0.65 (95% CI 0.61, 0.68) for model 3a, and 0.69 (95% CI 0.66, 0.72) for model 3b. The concordance between MRI and SF biomarkers was statistically significant only for effusion-synovitis and IL-8. CONCLUSION: Neither MRI-detected inflammation nor selected SF/serum inflammation biomarkers at 2 years postinjury predicted ROA or MROA at 5 years postinjury. Concordance between MRI and SF inflammatory biomarkers was weak.

Natural corollaries and recovery after acute ACL injury: the NACOX cohort study protocol.

INTRODUCTION: Anterior cruciate ligament (ACL) injury can result in joint instability, decreased functional performance, reduced physical activity and quality of life and an increased risk for post-traumatic osteoarthritis. Despite the development of new treatment techniques and extensive research, the complex and multifaceted nature of ACL injury and its consequences are yet to be fully understood. The overall aim of the NACOX study is to evaluate the natural corollaries and recovery after an ACL injury. METHODS AND ANALYSIS: The NACOX study is a multicentre prospective prognostic cohort study of patients with acute ACL injury. At seven sites in Sweden, we will include patients aged 15-40 years, within 6 weeks after primary ACL injury. Patients will complete questionnaires at multiple occasions over the 3 years following injury or the 3 years following ACL reconstruction (for participants who have surgical treatment). In addition, a subgroup of 130 patients will be followed with clinical examinations, several imaging modalities and biological samples. Data analyses will be specific to each aim. ETHICS AND DISSEMINATION: This study has been approved by the regional Ethical committee in Linköping, Sweden (Dnr 2016/44-31 and 2017/221-32). We plan to present the results at national and international conferences and in peer-reviewed scientific journals. Participants will receive a short summary of the results following completion of the study. TRIAL REGISTRATION NUMBER: NCT02931084.

Impact of treatment strategy and physical performance on future knee-related self-efficacy in individuals with ACL injury.

BACKGROUND: In people with anterior cruciate ligament (ACL) injury, high self-efficacy facilitates recovery, indicated by improved muscle function, reduced knee symptoms and increased physical activity. Impact of treatment on future self-efficacy is however not well investigated. The aims of the study were to 1) investigate knee-related self-efficacy 6 years after acute ACL injury in patients treated with exercise therapy alone or in combination with either early or the option of delayed ACL reconstruction (ACLR), and 2) to investigate associations between single-leg physical performance at various time points after ACL injury and knee self-efficacy at 6 years after injury. METHODS: Participants (n = 121) originated from the KANON-study (ISRCTN84752559), a treatment RCT including active adults with acute ACL injury treated with structured exercise therapy combined with early or the option of delayed ACLR. In this ancillary study, participants with knee self-efficacy data at 6 years (n = 89) were analyzed as treated; exercise therapy alone (n = 20), exercise therapy plus early ACLR (n = 46), and exercise therapy plus delayed ACLR (n = 23). The participants performed physical performance tests (hop, strength and balance) at the end the of exercise therapy (mean 10 (SD 6) months), and at 5 years, and rated their knee self-efficacy using Knee Self-Efficacy Scale (K-SES) questionnaire (0 to 10, worst to best) at 6 years. RESULTS: Median K-SES score for the total group (n = 89) was 7.8 (IQR 5.9-9.0). There were no differences between treatment groups in K-SES scores at 6 years nor in physical performance at any time point (p ≥ 0.097). Worse knee flexion strength LSI (rsp = 0.341, p = 0.042) at the end of the exercise therapy, and worse LSI for single-leg hop test (rsp = 0.310, p = 0.005) at the end of the exercise therapy and at 5 years, correlated moderately with worse knee-related self-efficacy at 6 years. Low associations were observed between the remaining physical performance tests and K-SES scores (rsp ≤ 0.265, p ≥ 0.045). CONCLUSION: Knee-related self-efficacy at 6 years after ACL injury did not differ between those treated with ACLR, performed early or as a delayed procedure, or exercise therapy alone. Good physical performance at the end of the exercise therapy, and at 5 years, appears to have a positive, yet small, impact on future knee-related self-efficacy.