2018 International Olympic Committee consensus statement on prevention, diagnosis and management
TITLE PAGE 1
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Title 3
New meniscal tears after anterior cruciate ligament injury 4
- A systematic review 5
6
List of authors Guri Ranum Ekås1 2 3 (corresponding author) 7
Email: g.r.ekas@nih.no 8
Phone number: +47 936 17 315 9
Mailing address: Statsminister Michelsens vei 65B, 10
5230 Paradis 11
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Clare Ardern4 13
C.Ardern@latrobe.edu.au 14
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Hege Grindem2 16
Hege.Grindem@nih.no 17
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Lars Engebretsen1 2 3 19
Lars.engebretsen@medisin.uio.no 20
Author affiliations:
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1 Division of Orthopaedic Surgery, Oslo University Hospital 22
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2 Oslo Sports Trauma Research Centre (OSTRC), Norwegian School of Sport Sciences, Oslo, 24
Norway 25
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3 Institute of Clinical Medicine, University of Oslo, Norway 27
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4Division of Physiotherapy, Linköping University, Linköping, Sweden 29
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ABSTRACT 31
Objective: To investigate the rate of new meniscal tears in children and adults after 32
treatment for anterior cruciate ligament (ACL) injury.
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Design: Systematic review (PROSPERO registration number CRD42016036788) 34
Methods: We searched Embase, Ovid Medline, Cochrane, CINAHL, SPORTDiscus, PEDro and 35
Google Scholar from inception to May 3, 2018. To be eligible for inclusion, articles had to 36
include patients with ACL injury (diagnosis confirmed by magnetic resonance imaging (MRI) 37
and/or diagnostic arthroscopy), report the number of meniscal tears at the time of ACL 38
injury diagnosis or at start of index treatment for ACL injury, and report the number of new 39
meniscal tears that subsequently occurred. Articles with <20 patients at follow-up, and 40
articles limited to ACL revision surgery or multi-ligament knee injuries were excluded. Two 41
independent reviewers screened articles, assessed eligibility, assessed risk of bias and 42
extracted data. We judged the certainty of evidence using the Grading of Recommendations 43
Assessment Development and Evaluation (GRADE) working group methodology.
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Results: Data from 9624 patients were included - 501 sustained a new meniscal tear. The 45
rate of new meniscal tears ranged from 0-52%; heterogeneity (I2 =93%) precluded data 46
pooling. The proportion of studies with high risk of selection, misclassification and detection 47
bias was 84%, 69% and 68%, respectively. Certainty of evidence was low.
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Conclusion: New meniscal tears occurred in 0-52% of patients following treatment for ACL 49
injury. The certainty of evidence was low. Clinicians should not rely on these uncertain 50
estimates when advising patients regarding treatment.
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Keywords ACL injury, ACL reconstruction, non-operative treatment, non-surgical treatment, 53
Active rehabilitation, rehabilitation, physiotherapy, secondary meniscal injury, ACL injury 54
treatment, 55
56
INTRODUCTION 57
Meniscal tears, especially those that result in meniscal loss or dysfunction, are the suspected 58
main culprits for long-term osteoarthritis1 and poor knee health2 3. Meniscal tears represent 59
a burden for the individual patient and for society. In the short term, patients may 60
experience pain, activity limitations and may need surgery; society bears expenses due to 61
health care and sick leave. The osteoarthritis corollary of meniscal tears over time, however, 62
is more burdensome4 5. 63
Protecting the meniscus must be central to decision-making in anterior cruciate ligament 64
(ACL) injury treatment6. Having an ACL reconstruction does not prevent knee osteoarthritis 65
(OA) after ACL injury, 1 7 but having meniscal tears, either at the time of the ACL injury or 66
subsequent to the ACL injury, does increase the risk 8-10. Preventing new meniscal tears is 67
therefore highly relevant for all patients with ACL injury and their treating clinicians. The risk 68
of new meniscal tears is relevant for all aspects of ACL injury treatment including surgery, 69
rehabilitation, return to sport and continued injury prevention.
70
Experts agree on the need for high-quality rehabilitation and secondary injury prevention for 71
all patients to prevent new injuries, but the indication for ACL reconstruction is debated11 12, 72
especially for paediatric patients11. Many clinicians advocate early ACL surgery to prevent 73
knee instability, hoping to prevent new injuries to the menisci and cartilage.13 Others 74
advocate a trial of active rehabilitation first to stabilize the knee through improved muscle 75
function14 1512 16. 76
A mitigating factor that may contribute to the lack of treatment consensus is that the 77
current literature on new or secondary meniscal tears after ACL injury is not consistent, and 78
may have methodological shortcomings11 17 18. Rates of new meniscal tears may differ across 79
age and treatment groups, and affording credence to studies with high risk of bias might 80
mislead clinical decisions 17 18 81
Clinicians need concise estimates of new meniscal tears after ACL injury to support clinical 82
decision making. Therefore, we aimed to investigate the rate of new meniscal tears after ACL 83
injury. We aimed to address 3 key questions:
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1. What is the incidence of new meniscal tears following treatment for ACL injury?
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2. Is there a difference in the incidence of new meniscal tears between patients who 86
had ACL reconstruction and patients who had non-operative treatment?
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3. Is there a difference in the incidence of new meniscal tears between patients who 88
were skeletally immature and patients who were skeletally mature at the time of 89
treatment for ACL injury?
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METHODS 92
This systematic review adhered to the Preferred Reporting Items for Systematic reviews and 93
Meta-Analysis (PRISMA) guidelines 19 20 and the review protocol, which was published 94
Prospective Register of Systematic Reviews (PROSPERO registration number:
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CRD42016036788).
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Eligibility criteria 99
To be included in the systematic review, articles had to include patients with ACL injury 100
(diagnosis confirmed by arthroscopy or MRI in all patients), report the number of meniscal 101
tears at the time of ACL injury diagnosis or start of ACL treatment (to provide a meniscal 102
baseline, so we could be sure that subsequent meniscal injuries were new injuries), and 103
report the number of patients with new meniscal tears occurring after the defined baseline.
104
We excluded literature reviews, non-English language articles, articles reporting on fewer 105
than 20 patients at final follow-up, and articles limited to ACL revision surgery or multi-106
ligament injuries18. 107
We defined a new meniscal tear as a meniscal tear that occurred after the ACL injury 108
baseline.
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Search strategy 110
We searched the following databases from inception to May 3, 2018: Embase, Ovid Medline, 111
Cochrane Library, CINAHL, SPORTDiscus, PEDro, and Google Scholar18. 112
We used three additional search approaches to identify any potentially eligible articles that 113
may have been missed in the electronic database search: (1) we manually searched the 114
reference lists of included studies and relevant systematic reviews, (2) we conducted 115
forward citation tracking using Google Scholar, (3) we manually searched the ePublication 116
lists for any newly published articles that may not have been indexed by the electronic 117
databases in the following journals: American Journal of Sports Medicine, Journal of Bone 118
and Joint Surgery, Arthroscopy, Bone & Joint Journal and British Journal of Sports 119
Medicine18. All search results were exported to an EndNote library and checked for duplicate 120
records. All identified articles were uploaded to Covidence (Veritas Health Innovation, 121
Melbourne, Australia. Available at www.covidence.org)21 to manage the article selection 122
process18. 123
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Article selection 125
First, two reviewers (GE and CA), independently screened titles and abstracts to identify 126
potentially relevant articles (figure 1). Second, all articles were reviewed in full text by GE 127
and CA. The inter-rater agreement for eligibility was moderate (Cohen’s kappa: 0.57)22. 128
Disagreements were resolved by consensus discussion, and a third author (HG) was 129
consulted if consensus could not be reached. If multiple publications reported on the same 130
study, we prioritised the article with the longest follow-up to avoid reporting on the same 131
patients twice. Eight studies were excluded23-30. 132
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Data extraction and risk of bias assessment 134
Data from all included articles were extracted independently and in duplicate18. GE 135
extracted data from all included articles; CA and HG extracted data from 50% of the articles 136
each. Disagreements were resolved by consensus discussions, and a third reviewer (either 137
CA or HG) was consulted if discrepancies could not be resolved. When needed, we contacted 138
study authors for clarification.
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As part of the data extraction strategy, we assessed the risk of bias with the Newcastle 140
Ottawa Quality Assessment Scale for Cohort Studies (supplementary file 1)31. We rated each 141
study on 8 items (domains), and these ratings were subsequently dichotomized into low and 142
high risk of bias based on predefined decision rules (supplementary file 2). Our standardised 143
data extraction table (supplementary file 3) and risk of bias assessment tool were pilot-144
tested before data extraction.
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Data analysis and synthesis 147
A biostatistician executed the data analysis according to our predefined analysis plan 148
(supplementary file 4). All analyses were conducted using Stata 15 (StataCorp. 2017. Stata 149
Statistical Software: Release 15. College Station, TX: StataCorp LLC).
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The main analysis was a proportion meta-analysis using Stata metaprop syntax to determine 151
the rate of new meniscal tears following treatment for ACL injury. Studies were stratified by 152
follow-up time categories: <2 years, 2-5 years, 5-10 years and > 10 years). We used a 153
random-effects model because we expected statistical heterogeneity. To ensure a 154
meaningful pooled estimate, analysed studies needed to be sufficiently homogeneous (I2 <
155
75%). We presented summary estimates for secondary meniscal tear rates graphically in a 156
forest plot, categorized by follow-up time. We assessed publication bias and small study 157
effects using a funnel plot32. Cohen’s kappa was calculated using Predictive Analytics 158
Software Statistics (v24.0 SPSS Inc., Chicago, Illinois, USA)22. We also used Stata melogit 159
syntax to examine the relationship between follow-up time and new meniscal tears.
160 161 162
Sensitivity analyses 163
We conducted sensitivity analyses based on (1) meniscal tear detection methods to assess 164
whether the diagnostic method affected the results, (2) selection bias as determined from 165
the risk of bias assessment, (3) detection bias as determined from the risk of bias 166
assessment, (4) whether all patients had meniscal repair at baseline or not, (5) and whether 167
patients had ACL reconstruction or other ACL surgery (e.g. ACL repair). Patients who had 168
other ACL surgery than ACL reconstruction had substantially higher rates of new meniscal 169
tears (other ACL surgery: 16 %, 95% CI: 6% to 29%, I2 =86.8%; all studies combined: 9 %, 95%
170
CI: 7% to 11%, I2 =84.7%). There were substantially lower rates of new meniscal tears in 171
studies where the meniscus injury diagnosis was based on clinical examination only (studies 172
with clinical diagnosis only: 0.03, 95% CI: 0.01 to 0.06, I2 =72%;all studies: 0.09, 95% CI: 0.07 173
to 0.11, I2 =85%). In the main analysis, we therefore excluded studies where patients had 174
other ACL surgery than ACL reconstruction, and studies where the meniscus injury diagnosis 175
was based on clinical examination only.
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After removing these studies, the statistical heterogeneity remained high (I2=93%). To avoid 177
presenting a potential misleading pooled estimate we presented the rates of the different 178
studies instead of a pooled estimate.
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Finally, we completed an additional post hoc sensitivity analysis to evaluate the effect of the 180
largest study on the results (Davis et al.33, n = 4087). When we excluded this study from 181
analysis, the I2 statistic was >75% and the pooled estimate for the 2-5 year follow-up 182
category was not substantially changed. Therefore, we retained Davis et al.33 in the analyses.
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184 185
Subgroup analyses 186
Predefined subgroups were (1) patients treated with ACL reconstruction compared to non-187
operative treatment, and (2) skeletally immature patients compared to skeletally mature 188
patients. We intended to use the Stata melogit syntax to compare the rate of new meniscal 189
tears in these subgroups. However, substantial heterogeneity, even after exclusion of 190
studies with characteristics that skewed the results, precluded meaningful subgroup 191
comparisons.
192 193
Strength of recommendations and certainty of evidence 194
We judged the certainty of evidence using the Grading of Recommendations Assessment 195
Development and Evaluation working group methodology (GRADE) 196
(www.gradeworkinggroup.org)34. We considered potential limitations due to risk of bias, 197
inconsistency, indirectness, imprecision and publication bias, and judged high, moderate, 198
low or very low certainty34 3536. We used GRADEpro (GRADEpro GDT: GRADEpro Guideline 199
Development Tool; McMaster University, 2015; Evidence Prime, Inc.; gradepro.org) to create 200
the evidence profile. The judgement reasoning is described in detail in supplementary file 5.
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Results 203
Seventy-five studies were included for qualitative synthesis (Figure 1), and 54 studies (9624 204
patients) were appropriate for quantitative synthesis (meta-analysis). The reasons for 205
excluding articles from meta-analysis were: clinical diagnosis of meniscal tear only (10 206
studies27 37-45 and one additional study arm16 ), other ACL surgery than ACL reconstruction (4 207
studies)46-49, or both (2 studies)50 51. We excluded studies with unknown number of patients 208
with new meniscal injuries (4 studies)52-55. We made a post hoc decision to exclude one 209
study with patients with partial ACL tears56. 210
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Study characteristics 212
Twenty-five of 75 included studies (33%) had a prospective design (17 randomized 213
controlled trials, 8 prospective case series), and 50 studies (67%) had a retrospective design 214
(50 retrospective case series) (see supplementary file 6 for characteristics of all included 215
studies). The follow-up period ranged from 4 months to 20 years. Fifty-seven of 75 studies 216
(75%) had at least 2 years follow-up. The follow-up rate was higher than 80% in 41 of 75 217
studies (55%).
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The 75 included studies had 11707 individual patients at inclusion. The smallest study 219
included 20 patients, and the largest included 4087 patients (median 72 patients). At least 220
4143 (35%) included patients were women; sex was not reported in 10 studies. Six studies 221
included only paediatric patients (all patients were skeletally immature or under 16 years at 222
ACL injury); 31 studies included only skeletally mature patients. Twenty-seven studies 223
included a mixed population of patients aged under and over 16 years or did not clarify 224
skeletal maturity. Study population was unclear in 13 studies. Forty-five studies only 225
included patients with ACL reconstruction. Eleven studies only included patients with non-226
operative treatment.
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In 13 studies (17% of 75), all patients had MRI or arthroscopy at follow-up; the assessor was 228
independent in two studies57 58. In 32 studies (43% of 75), new meniscus injury was detected 229
by clinical examination followed by arthroscopy and/or MRI on indication (i.e. in some 230
unclear. In 51 (68% of 75) studies, the authors only reported surgically treated tears and 232
most of these studies (49 studies) only reported surgeries at the study centre. Four studies 233
described the total number of meniscus injuries, but not the number of injured patients.
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These studies were excluded from meta-analysis.
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Risk of bias within domains for individual studies 237
All included studies had limitations in at least 2 bias domains (Table 1, Supplementary file 7).
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We judged 51 to 63 studies (68-84% of 75 studies) were at high risk of bias for the domains:
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Representativeness of the exposed cohort (selection bias), Demonstration that the outcome 240
of interest was not present at start of the study (misclassification bias) and Assessment of the 241
outcome (detection bias). Two studies assessed the outcome in all patients in the study with 242
appropriate measures by independent examiner. Follow-up time and rate was adequate in 243
57 (76%) and 41 (55%) studies (defined as long enough for outcome to occur; at least 2 years 244
and follow-up rate over 80%).
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Table 1. Risk of bias assessment 246
Newcastle-Ottawa scale domain
Evaluation of risk of bias in included studies Not appropriate High riskN (%)
Unclear N (%)
Low risk N (%)
Selection
Representativeness of exposed cohort 63 (84%) 1 (1%) 11 (15%)
Representativeness of the controls 69 (92%) 1 (1.3) 5 (6.7%)
Demonstration that outcome of interest was not present at start of the study
51 (68%) 5 (7%) 19 (25%)
Ascertainment of the exposure 75 (100%)
Comparability
Comparability of cohorts 73 (97%) 1 (1.3%) 1 (1.3%)
Outcome
Assessment of outcome 52 (69%) 21 (28%) 2 (3%)
Was follow-up long enough for outcomes to occur
15 (20%) 3 (4%) 57 (76%)
Adequacy of follow-up of cohorts 25 (33%) 9 (12%) 41 (55%)
247 248
Incidence of new meniscus tears after treatment for ACL injury 249
Among the 9624 patients included for quantitative analysis, 501 sustained new meniscal 250
tears. The rate of new meniscal tears varied from 0 to 52% (Figure 2). Minimum to maximum 251
rates were: 0-21% for < 2 years follow-up, 0-29% for 2-5 years follow-up, 5-52% for 5-10 252
years follow-up and 4-31% for >10 years follow-up (Figure 2). Meta-regression demonstrated 253
that increased follow-up time was associated with higher meniscal rates, with 12% higher 254
odds of meniscal injury per year of follow-up (OR: 1.12, 95% CI: 1.05-1.20, p<0.001).
255
Results from the ACL treatment and skeletal maturity subgroups are presented in 256
Supplementary file 8. There was no clear evidence of small study effects (Supplementary file 257
9).
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Figure 2 Forest plot of new meniscal tear rate in individual studies categorized by follow-up 259
time without pooled estimate.
260
We downgraded the certainty of evidence due to risk of bias, inconsistency and indirectness 261
(judgements explained in Supplementary file 5). Overall, the certainty of evidence regarding 262
risk of new meniscal tears after ACL injury treatment was very low.
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Table 2 GRADE Evidence Profile 264
Discussion
265
The rate of new meniscal tears after treatment for ACL injury varied from 0 to 52%.
266
Heterogeneity precluded meta-analysis and a meaningful pooled estimate. Heterogeneity 267
also precluded a meaningful comparison by treatment or skeletal maturity. Based on our risk 268
of bias assessment and grading of the certainty of evidence, we can firmly conclude that the 269
body of evidence on new meniscal tears after ACL injury treatment has major scientific 270
limitations. These findings should inform clinical practice and stimulate high-quality 271
research.
272
The very low certainty of evidence in this systematic review challenges the clinical dogma 273
that early ACL surgery is necessary to protect the meniscus. Patients and clinicians must 274
recognise that there is insufficient evidence to support this treatment strategy in all patients.
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Why are the results so variable?
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The results of the included studies may be influenced by clinical or methodological 278
diversity3236. In this section, we address 4 issues that might impact on the certainty of the 279
evidence in our systematic review.
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It is likely that studies where meniscal diagnosis was performed clinically (no MRI or 281
arthroscopy) underestimated the rate of new meniscal tears. Meniscal injury rates were 282
substantially higher for patients who had other ACL surgery than those who had ACL 283
reconstruction (i.e. ACL repair, ACL repair with augmentation, extra-articular tenodesis). We 284
excluded studies where meniscal diagnosis was performed clinically, and studies where 285
patients had other ACL surgery. However, the heterogeneity remained high. There may be 286
multiple explanations for the heterogeneity including clinical factors (age, sex, BMI, skeletal 287
maturity, activity level, return to sport, surgical treatment (including previous meniscus 288
treatment), rehabilitation, prevention) and methodological factors36 (design, patient sample, 289
method of detecting meniscal tears, definition/reporting of meniscal tears, follow-up rate, 290
follow-up time).
291
We found patterns in our results that may illustrate the problem of selection bias and how 292
this may affect the rate of new meniscal tears. Studies that included non-operated patients 293
scheduled for surgery dominated the rates of new meniscal tears in in the <2 years, 2-5 294
years and not reported follow-up category59-61. There were no studies which included 295
exclusively patients scheduled for surgery in the 5-10 years and >10 years follow-up 296
category. Because these patients are a selected group who probably do not cope well with 297
their injury, the rate of new meniscal tears in these patients may be over-estimated 298
compared to non-operated patients in general. Similarly, assessing the rate of new meniscal 299
tears in selected copers will under-estimate the rate in non-operated patients. To estimate 300
the true incidence of new meniscal tears after non-operative treatment, patients should be 301
followed prospectively from treatment initiation to include both copers and non-copers.
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Most studies (68%) reported cases of new meniscal surgeries, not meniscal injuries. This 303
information is relatively straightforward to extract from a medical record/database, and is 304
less time consuming and cheaper than examining all patients for new meniscal injuries.
305
However, reporting only meniscal surgeries and relying on medical charts alone is likely to 306
underestimate the rate of new meniscal injuries. Injuries diagnosed or treated elsewhere, 307
and injuries treated non-operatively (or not detected) are all unlikely to be registered.
308
Early return to sport62 and high activity level63 are important confounders for new knee 309
trauma (i.e. new meniscal injuries) after ACL injury. The studies had insufficient information 310
about post-injury activity level and return to high risk sports, and we were unable to account 311
for this factor in our meta-analysis. Between-study differences in risk exposure may have 312
contributed to heterogeneity in results.
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314
What is already known?
315
Because our review question focused on identifying new meniscal tears, we required 316
included studies to report meniscal injuries at at least 2 time points: baseline (close to 317
treatment of ACL injury) and at least 1 follow-up. As a result, a large number of studies were 318
excluded - they either did not provide a baseline rate of meniscal injuries (28 studies) or 319
follow-up meniscal status to identify new meniscal injuries (137 studies). These studies are
follow-up meniscal status to identify new meniscal injuries (137 studies). These studies are