Distinct myofibre domains of the human myotendinous junction revealed by single-nucleus RNA sequencing.

The myotendinous junction (MTJ) is a specialized domain of the multinucleated myofibre that is faced with the challenge of maintaining robust cell-matrix contact with the tendon under high mechanical stress and strain. Here, we profiled 24,124 nuclei in semitendinosus muscle-tendon samples from three healthy males by using single-nucleus RNA sequencing (snRNA-seq), alongside spatial transcriptomics, to gain insight into the genes characterizing this specialization in humans. We identified a cluster of MTJ myonuclei represented by 47 enriched transcripts, of which the presence of ABI3BP, ABLIM1, ADAMTSL1, BICD1, CPM, FHOD3, FRAS1 and FREM2 was confirmed at the MTJ at the protein level in immunofluorescence assays. Four distinct subclusters of MTJ myonuclei were apparent, comprising two COL22A1-expressing subclusters and two subclusters lacking COL22A1 expression but with differing fibre type profiles characterized by expression of either MYH7 or MYH1 and/or MYH2. Our findings reveal distinct myonuclei profiles of the human MTJ, which represents a weak link in the musculoskeletal system that is selectively affected in pathological conditions ranging from muscle strains to muscular dystrophies.

Good physical function but reduced quality of life in children 3 years after ACL reconstruction.

PURPOSE: To assess children's physical function and subjective knee status 1 and 3 years after anterior cruciate ligament (ACL) reconstruction. It was hypothesised that there was no difference between the operated and normal legs in relation to physical strength and function, that there was <-2 mm side-to-side difference in knee laxity, and that the subjective knee function was better 3 years after ACL reconstruction compared to 1 year after. METHODS: Children (<16 years of age) who had an ACL reconstruction had follow-up with physical function tests (four hop tests and strength measurement in a power rig [PR]), anterior knee laxity (measured using a Rolimeter) and patient-reported outcome measures (Pedi-International Knee Documentation Committee [IKDC] and Knee injury and Osteoarthritis Outcome Score [KOOS]-Child) 1 and 3 years postoperatively. Changes from 1- to 3-year follow-up were evaluated with a paired t test. RESULTS: Out of 148 ACL reconstructed children, 60 had all measures. The four hop tests and the PR all yielded a Limb Symmetry Index >90% at both follow-ups. There was a significant improvement from 1- to 3-year follow-up in two-hop tests (6 m on time and crossover hop). Side-to-side knee laxity was >2 mm in four children at 1- and 3-year tests. Pedi-IKDC scores increased, and KOOS-Child improved significantly from 1 to 3 years in two of the five domains: 'Sport' and 'Quality of life', but scores were lower than in a cohort of normal children. CONCLUSION: The children had good objective physical function 1 and 3 years after ACL reconstruction. However, scores from the KOOS-Child sport-specific function and quality of life domains were lower than in normal children. LEVEL OF EVIDENCE: Level II.

A clinical guide to the medial ligaments of the ankle: Anatomy, function, diagnosis of injuries and treatment of instability-a narrative review.

BACKGROUND: The aim was to provide an update on anatomy and function of the medial ankle ligaments, diagnosis of their injuries and treatment of medial ankle instability. METHODS: Literature search on PubMed. RESULTS: Injuries to the deltoid ligament are not uncommon in relation to malleolar fractures and ankle sprains. Chronic instability may lead to ankle osteoarthritis. However, there is no consensus on diagnostic criteria (clinically, by imaging and by arthroscopy), on indications for non-operative and operative treatment, and on standards for repair and reconstruction of the ligament complex. There is no current evidence to support acute repair of deltoid ligament injury. Reports on the effect of isolated deltoid ligament reconstruction are very sparse. CONCLUSION: There is a need for a focused effort to establish evidence for all aspects of deltoid ligament injury.

Larger interface area at the human myotendinous junction in type 1 compared with type 2 muscle fibers.

The myotendinous junction (MTJ) is structurally specialized to transmit force. The highly folded muscle membrane at the MTJ increases the contact area between muscle and tendon and potentially the load tolerance of the MTJ. Muscles with a high content of type II fibers are more often subject to strain injury compared with muscles with type I fibers. It is hypothesized that this is explained by a smaller interface area of MTJ in type II compared with type I muscle fibers. The aim was to investigate by confocal microscopy whether there is difference in the surface area at the MTJ between type I and II muscle fibers. Individual muscle fibers with an intact MTJ were isolated by microscopic dissection in samples from human semitendinosus, and they were labeled with antibodies against collagen XXII (indicating MTJ) and type I myosin (MHCI). Using a spinning disc confocal microscope, the MTJ from each fiber was scanned and subsequently reconstructed to a 3D-model. The interface area between muscle and tendon was calculated in type I and II fibers from these reconstructions. The MTJ was analyzed in 314 muscle fibers. Type I muscle fibers had a 22% larger MTJ interface area compared with type II fibers (p < 0.05), also when the area was normalized to fiber diameter. By the new method, it was possible to analyze the structure of the MTJ from a large number of human muscle fibers. The finding that the interface area between muscle and tendon is higher in type I compared with type II fibers suggests that type II fibers are less resistant to strain and therefore more susceptible to injury.

Pedi-IKDC exhibits questionable measurement properties in a cohort of pediatric patients with ACL rupture.

BACKGROUND: Pedi-IKDC is commonly used to evaluate anterior cruciate ligament (ACL) deficiency in children. However, its construct validity has not been thoroughly assessed. The aim was to examine the measurement properties of the Pediatric International Knee Documentation Committee (Pedi-IKDC) by modern test theory (MTT) models, confirmatory factor analysis (CFA), and item response theory (IRT). METHODS: The cohort consisted of all children and adolescents in Denmark (n = 535, age 9-16) treated with physeal-sparing ACL reconstruction 2011-2020. Patient-reported outcome measure (PROM) data were collected before surgery and at 1 year follow-up. Structural validity of Pedi-IKDC was assessed with MTT models. Reliability was reported as McDonalds coefficient omega. Responsiveness was evaluated with standardized response means. RESULTS: Sufficient PROM data were available for 372 patients. The original unidimensional construct did not fit CFA model expectations neither before surgery (χ2 = 462.0, df = 163, p < 0.0001; RMSEA: 0.109, CFI: 0.910, TFI: 0.895) nor at follow-up. Neither did a two-factor CFA model with "Symptoms" and "Sports activities" as individual subscales (χ2 = 455.6, df = 162, p < 0.0001) nor a bifactor model (χ2 = 338.9, df = 143, p < 0.0001), although fit indices improved with the latter (RMSEA: 0.094, CFI: 0.941, TFI: 0.922). The IRT models confirmed this pattern. The scale was responsive (SRM 1.66 (95% CI: 1.46-1.88)). Coefficient omega values were 0.866 before surgery and 0.919 at follow-up. CONCLUSIONS: The Pedi-IKDC exhibited inadequate structural validity. Neither the original construct, a two-factor model, nor bifactor models fitted data well. We advise that data obtained by Pedi-IKDC are interpreted with caution.

Comparison between conventional MRI and weight-bearing positional MRI reveals important differences in radiological measurements of the patellofemoral joint.

OBJECTIVE: To compare radiological measurements of the patellofemoral joint (PFJ) morphology and measurement reproducibility across the following scanning modalities: (a) 3 T supine MRI, (b) 0.25 T supine MRI and (c) standing 0.25 T MRI. METHODS: Forty patients referred to MRI of the knee were scanned by high field 3 T MRI in supine position and low field 0.25 T positional (pMRI) in supine and standing positions. Radiological measurements for assessment of femoral trochlear morphology, patellar tracking, patellar height and knee flexion angle were compared across scanning situations by one-way repeated-measures ANOVA. Measurement reliability and agreement were assessed by calculation of ICC, SEM and MDC. RESULTS: Patellar tracking differed across scanning situations, particularly between 3.0 T supine and 0.25 T standing position. Mean differences are the following: patella bisect offset (PBO): 9.6%, p ≤ 0.001; patellar tilt angle (PTA): 3.1°, p ≤ 0.001; tibial tuberosity-trochlear groove distance (TT-TG): 2.7 mm, p ≤ 0.001). Measurements revealed slight knee joint flexion in supine and slight hyperextension in the standing position (MD: 9.3°, P ≤ 0.001), likely related to the observed differences in patellar tracking. Reproducibility was comparable across MRI field strengths. In general, PBO, PTA and TT-TG were the most robust measurements in terms of reproducibility and agreement across scanning situations (ICC range: 0.85-0.94). CONCLUSION: Significant differences in important patellofemoral morphology measurements were observed between supine and standing MRI scanning positions. These were unlikely due to physiological factors such as changes in joint loading but rather induced by slight differences in knee flexion angle. This emphasises the need to standardise knee positioning during scanning, particularly for weight-bearing positional MRI before clinical use.

Functional performance tests, clinical measurements, and patient-reported outcome measures do not correlate as outcomes 1 year after anterior cruciate ligament reconstruction.

PURPOSE: The results after anterior cruciate ligament reconstruction (ACLR) are evaluated by laxity measures, functional tests, and patients' perception by patient-reported outcome measures (PROMs). It is not known, if one of these evaluation instruments is representative or if outcome scores from all must be reported to obtain a full evaluation of the condition. The aim was to study the correlations between these three types of outcomes 1 year after primary ACLR. METHOD: All adult patients (range 18-45 years) who had an ACLR between 1.1.2019 and 31.12.2021 were offered 1-year follow-up by an independent observer. Preoperative information about knee laxity and peroperative information about the condition of menisci and cartilage were registered. At 1-year follow-up clinical and instrumented knee stability and function assessed by four different hop tests were registered. Patients completed four PROMs (the Subjective International Knee Documentation Committee (IKDC) score, the Knee Numeric-Entity Evaluation Score (KNEES-ACL), the Knee injury and Osteoarthritis Outcome Score (KOOS) and the Lysholm score) and Tegner activity scale and answered anchor questions regarding satisfaction and willingness to repeat the operation. RESULTS: A total of 190 adults attended the 1-year follow-up and 151 had all assessments. There were only a few positive and weak correlations between performance tests and PROMS and between clinical measurements and PROMS (r = 0.00-0.38), and the majority were of negligible strength. Tegner score had in general the highest correlation (low to moderate). The highest correlation was 0.53 (moderate) between the anchor question about patient satisfaction and Lysholm/IKDC scores. There was no difference in the correlations depending on meniscal condition. CONCLUSIONS: In ACLR patients there was no clinically relevant correlation between scores obtained by PROMs, a battery of functional performance tests and instrumented laxity of the knee at 1-year follow-up. Therefore, one type of outcome cannot represent the others. This is an argument for always to include and report all three types of outcomes, and conclusions based on one type of outcome may not be sufficient. LEVEL OF EVIDENCE: II.

No correlation between performance tests, clinical measurements and data from patient-reported outcome measures (PROM) in children reconstructed for anterior cruciate ligament injury.

PURPOSE: To investigate if patient-reported outcome measures (PROMs), functional tests and clinical measures correlate well in children after reconstruction of the anterior cruciate ligament (ACL). It was hypothesized that these outcomes correlate, so it is sufficient to report only one of them. METHODS: A consecutive group of children (< 16 years old) who had an ACL reconstruction, were prospectively followed and assessed after 1-year with Pedi-IKDC and KOOS-Child, instrumented laxity measurement, range of motion, extension strength and four performance tests. Relations between the different outcomes were calculated by partial correlation coefficient analysis, controlling for gender, age, height, and weight. RESULTS: Outcomes were available for 141 of 163 children. There were only few positive and weak correlations between performance tests and PROM scores and between clinical measurements and PROM scores. There were weak to strong correlations between the scores from Pedi-IKDC and the scores from each of the five domains of KOOS-Child and a weak to moderate correlation between the different domains of KOOS-Child. Similar correlations were found between the different performance tests. CONCLUSION: For children who had their ACL reconstructed there was no clinically important correlation between scores obtained by PROMs, a battery of functional performance tests and instrumented laxity of the knee at 1-year follow-up. This is an argument for always to include and report all three types of outcomes. LEVEL OF EVIDENCE: Level II.

Patients in high- and low-revision hospitals have similar outcomes after primary knee arthroplasty: 1-year postoperative results from the Danish prospective multicenter cohort study, SPARK.

PURPOSE: It is well-known that revision rates after primary knee arthroplasty vary widely. However, it is uncertain whether hospital revision rates are reliable indicators of general surgical quality as defined by patients. The SPARK study compared primary knee arthroplasty surgery at three high-volume hospitals whose revision rates differed for unknown reasons. METHODS: This prospective observational study included primary knee arthroplasty patients (total, medial/lateral unicompartmental and patellofemoral) in two low-revision hospitals (Aarhus University Hospital and Aalborg University Hospital Farsø) and one high-revision hospital (Copenhagen University Hospital Herlev-Gentofte). Patients were followed from preoperatively (2016-17) to 1-year postoperatively with patient-reported outcome measures including Oxford Knee Score (OKS), EQ-5D-5L and Copenhagen Knee ROM (range of motion) Scale. The surgical outcomes were compared across hospitals for patients with comparable grades of radiographic knee osteoarthritis and preoperative OKS. Statistical comparisons (parametric and non-parametric) included all three hospitals. RESULTS: 97% of the 1452 patients who provided baseline data (89% of those included and 56% of those operated) responded postoperatively (90% at 1 year). Hospitals' utilization of unicompartmental knee arthroplasties differed (Aarhus 49%, Aalborg 14%, and Copenhagen 22%, p < 0.001). 28 patients had revision surgery during the first year (hospital independent, p = 0.1) and were subsequently excluded. 1-year OKS (39 ± 7) was independent of hospital (p = 0.1), even when adjusted for age, sex, Body Mass Index, baseline OKS and osteoarthritis grading. 15% of patients improved less than Minimal Important Change (8 OKS) (Aarhus 19%, Aalborg 13% and Copenhagen 14%, p = 0.051 unadjusted). Patients with comparable preoperative OKS or osteoarthritis grading had similar 1-year results across hospitals (OKS and willingness to repeat surgery, p ≥ 0.087) except for the 64 patients with Kellgren-Lawrence grade-4 (Aarhus 4-6 OKS points lower). 86% of patients were satisfied, and 92% were "willing to repeat surgery", independent of hospital (p ≥ 0.1). Hospital revision rates differences diminished during the study period. CONCLUSIONS: Patients in hospitals with a history of differing revision rates had comparable patient-reported outcomes 1 year after primary knee arthroplasty, supporting that surgical quality should not be evaluated by revision rates alone. Future studies should explore if revision rate variations may depend as much on revision thresholds and indications as on outcomes of primary surgery. LEVEL OF EVIDENCE: Level II (Prospective cohort study).

Hospital variation in revision rates after primary knee arthroplasty was not explained by patient selection: baseline data from 1452 patients in the Danish prospective multicenter cohort study, SPARK.

PURPOSE: Revision rates following primary knee arthroplasty vary by country, region and hospital. The SPARK study was initiated to compare primary surgery across three Danish regions with consistently different revision rates. The present study investigated whether the variations were associated with differences in the primary patient selection. METHODS: A prospective observational cohort study included patients scheduled Sep 2016 Dec 2017 for primary knee arthroplasty (total, medial/lateral unicompartmental or patellofemoral) at three high-volume hospitals, representing regions with 2-year cumulative revision rates of 1, 2 and 5%, respectively. Hospitals were compared with respects to patient demographics, preoperative patient-reported outcome measures, motivations for surgery, implant selection, radiological osteoarthritis and the regional incidence of primary surgery. Statistical tests (parametric and non-parametric) comprised all three hospitals. RESULTS: Baseline data was provided by 1452 patients (89% of included patients, 56% of available patients). Patients in Copenhagen (Herlev-Gentofte Hospital, high-revision) were older (68.6 ± 9 years) than those in low-revision hospitals (Aarhus 66.6 ± 10 y. and Aalborg (Farsø) 67.3 ± 9 y., p = 0.002). In Aalborg, patients who had higher Body Mass Index (mean 30.2 kg/m2 versus 28.2 (Aarhus) and 28.7 kg/m2 (Copenhagen), p < 0.001), were more likely to be male (56% versus 45 and 43%, respectively, p = 0.002), and exhibited fewer anxiety and depression symptoms (EQ-5D-5L) (24% versus 34 and 38%, p = 0.01). The preoperative Oxford Knee Score (23.3 ± 7), UCLA Activity Scale (4.7 ± 2), range of motion (Copenhagen Knee ROM Scale) and patient motivations were comparable across hospitals but varied with implant type. Radiological classification ≥ 2 was observed in 94% (Kellgren-Lawrence) and 67% (Ahlbäck) and was more frequent in Aarhus (low-revision) (p ≤ 0.02), where unicompartmental implants were utilized most (49% versus 14 (Aalborg) and 23% (Copenhagen), p < 0.001). In the Capital Region (Copenhagen), the incidence of surgery was 15-28% higher (p < 0.001). CONCLUSION: Patient-reported outcome measures prior to primary knee arthroplasty were comparable across hospitals with differing revision rates. While radiographic classifications and surgical incidence indicated higher thresholds for primary surgery in one low-revision hospital, most variations in patient and implant selection were contrary to well-known revision risk factors, suggesting that patient selection differences alone were unlikely to be responsible for the observed variation in revision rates across Danish hospitals. LEVEL OF EVIDENCE: II, Prospective cohort study.

Combined anterior cruciate ligament revision with reconstruction of the antero-lateral ligament does not improve outcome at 2-year follow-up compared to isolated acl revision; a randomized controlled trial.

PURPOSE: It is essential to obtain rotational stability of the knee after anterior cruciate ligament reconstruction (ACL-R) and it is suggested that a supplementary reconstruction of the antero-lateral ligament (ALL-R) may supports this. Theoretically, ALL-R may be particularly advantageous to support revision of failed ACL-Rs. It was hypothesized that ACL revision combined with ALL-R will result in superior outcome compared to isolated ACL revision. METHODS: The study was designed as a randomized controlled trial. Patients eligible for first time ACL revision were randomized to either isolated ACL revision (- ALL group) or ACL revision combined with a single-stranded allograft ALL-reconstruction (+ ALL group). Patient reported outcomes and function were evaluated at two-year follow-up by KNEES-ACL, KOOS, and Tegner activity scale. Objective knee laxity was evaluated at one-year follow-up using an instrumented Rolimeter test, the pivot shift test, and a manual Lachman test. RESULTS: A total of 103 patients were enrolled with 49 patients randomized to the + ALL group and 54 patients in the - ALL group. There were no differences at baseline between groups regarding age, gender, body mass index, preoperative patient reported outcome scores and concomitant meniscus or cartilage injury. The ACL revision was performed with an allograft in 10 patients (20%) in the + ALL group and 8 patients (15%) in the -ALL group. At follow-up there was no significant difference between the groups in patient reported outcome scores and clinical knee laxity. CONCLUSION: Supplementary ALL-R does not improve subjective outcome of first time ACL revision at two-years and clinical knee stability at one-year follow-up compared to isolated ACL revision. LEVEL OF EVIDENCE: Level I.

Similar outcomes after anterior cruciate ligament reconstruction in paediatric and adult populations: a 1-year follow-up of 506 paediatric operations in Denmark.

PURPOSE: To present 1-year results after all paediatric anterior cruciate ligament (ACL) reconstructions in Denmark (5.9 M inhabitants) for the 10½ year period, 1 July 2011 to 31 December 2021. METHODS: All children who had an ACL reconstruction were enrolled. They were asked to complete Pedi-IKDC preoperatively and at 1-year follow-up. Independent observers performed pivot shift test and instrumented laxity assessment preoperatively and at 1-year follow-up. RESULTS: The median age of the 506 children (47.2% girls) was 14.3 years (9.3-15.9). The Pedi-IKDC score increased from preoperatively 61.6 ± 15.8 (mean ± SD) to 85.9 ± 13.0 at 1-year follow-up (p < 0.0001). There were concomitant injuries (to meniscus and/or cartilage) in 49.9%, but these children had preoperative and follow-up Pedi-IKDC scores similar to the scores for children with isolated injury to ACL (n. s.). Instrumented anterior laxity was 4.3 ± 1.4 (mean ± SD) mm preoperatively and 1.4 ± 1.4 mm at follow-up (p < 0.0001). Preoperatively, 3% had no pivot shift whilst this was the case for 68% postoperatively (p < 0.0001). Twenty-five children (5.6%) had 4 mm instrumented laxity or more relative to the unoperated knee at follow-up. Two patients (0.4%) had an operatively treated deep infection, three (0.5%) were operated on for reduced range of motion and two (0.4%) had a revision ACL reconstruction. CONCLUSION: ACL reconstruction resulted in a clinically meaningful increase in Pedi-IKDC, an improved instrumented stability, a reduction in the grade of pivot shift and the complication rate was low at 1-year follow-up. The risk of graft insufficiency at 1-year follow-up was the same as in an adult population. LEVEL OF EVIDENCE: II.

Nestin and osteocrin mRNA increases in human semitendinosus myotendinous junction 7 days after a single bout of eccentric exercise.

The myotendinous junction (MTJ), a specialized interface for force transmission between muscle and tendon, has a unique transcriptional activity and is highly susceptible to muscle strain injury. Eccentric exercise training is known to reduce this risk of injury, but knowledge of the influence of exercise on the MTJ at the molecular and cellular levels is limited. In this study, 30 subjects were randomized to a single bout of eccentric exercise 1 week prior to tissue sampling (exercised) or no exercise (control). Samples were collected from the semitendinosus as part of reconstruction of the anterior cruciate ligament and divided into fractions containing muscle, MTJ and tendon, respectively. The concentrations of macrophages and satellite cells were counted, and the expression of genes previously known to be active at the MTJ were analyzed by real-time-quantitative PCR. An effect of the single bout of exercise was found on the expression of nestin (NES) and osteocrin (OSTN) mRNA in the MTJ and tendon fractions. Genes earlier identified at the MTJ (COL22A1, POSTN, ADAMTS8, MNS1, NCAM1) were confirmed to be expressed at a significantly higher level in the MTJ compared to muscle and tendon but were unaffected by exercise. In the exercise group a higher concentration of macrophages, but not of satellite cells, was seen in muscle close to the MTJ. The expression of NES and OSTN was higher in human semitendinosus MTJ 1 week after a single session of heavy eccentric exercise. Based on these results, NES and OSTN could have a part in explaining how the MTJ adapts to eccentric exercise.

KOOS-Child exhibits inadequate structural validity in a cohort of paediatric patients with ACL deficiency.

OBJECTIVES: Knee injury and Osteoarthritis Outcome Score (KOOS)-Child is a modification of the adult KOOS aiming to evaluate knee injury, including ACL deficiency. However, the measurement properties of KOOS-Child have not been assessed in a cohort of children with ACL deficiency. We aimed to study the structure of KOOS-Child using modern test theory models (Rasch analysis and confirmatory factor analysis (CFA)). METHODS: Data were collected prospectively in a cohort of children with ACL deficiency at three time points: before-and-after ACL surgery, and at 1-year follow-up. For each subscale, structural validity through the fit of a CFA model was evaluated for 153 respondents. Modification indices were examined to find the model of best fit, confirmed using Rasch analysis. Responsiveness was reported for each subscale. Reliability was calculated for each item. Floor and ceiling effects, and Person-item distribution were reported. RESULTS: All subscales showed inadequate fit to a unidimensional CFA model. Rasch analysis confirmed these results. Adjusting the subscales improved model fit, although this was still quite poor, except for the quality of life subscale. With one exception, all items demonstrated ceiling effects. Person-item distribution confirmed this. Due to lack of fit, reliability was not reported. All subscales were able to detect change from baseline to 1-year follow-up. CONCLUSIONS: KOOS-Child exhibits inadequate measurement properties in its current form for children with ACL deficiency. Suggestions to make the subscales fit the models better and improve accuracy of KOOS-Child are presented. However, the large ceiling effects observed may reduce sensitivity and induce type 2 errors.

Acetabular retroversion does not affect outcome in primary hip arthroscopy for femoroacetabular impingement.

PURPOSE: The surgical treatment of femoral-acetabular impingement syndrome (FAIS) in patients with acetabular retroversion (AR) is arthroscopical or by a reverse periacetabular osteotomy (PAO). The purpose of the present study was to investigate the results after arthroscopic treatment of FAIS in patients with and without radiographic signs of AR in a large, prospective cohort from the Danish Hip Arthroscopy Registry (DHAR). The hypothesis was there is no difference in clinical outcome between the two groups. METHODS: Data on 4914 hip arthroscopies performed during 2012-2019 were obtained from DHAR. Patients with radiographic signs of osteoarthritis (Tönnis > 1), hip dysplasia (CEA < 25°), other hip pathologies or previous hip surgery were excluded. The clinical outcomes for patients with AR [defined by a positive posterior wall sign (PWS) in combination with a positive Ischial Spine Sign (ISS)] and patients without AR (no PWS, no ISS) were analyzed 1 and 2 years after surgery. The primary outcomes were the six domains of the Copenhagen Hip and Groin Outcome score (HAGOS), while secondary outcomes were the Hip Sports Activity Scale (HSAS), a visual analogue pain scale (VAS) and a numeric rating scale (NRS) for pain. RESULTS: A total of 3135 hip arthroscopies were included, of which 339 had AR, 1876 did not, and 920 presented one of the two signs (PWS and ISS). There were no statistically significant differences 1 and 2 years after surgery (n.s.) between patients with and without AR in HAGOS domain scores, HSAS, VAS, or NRS. Both groups showed improvement at both follow-ups. The two groups did not differ in relation to intraoperative findings and the procedures they have had. CONCLUSION: The outcome 1 and 2 years after arthroscopic treatment of FAIS is not different for patients with and without AR. LEVEL OF EVIDENCE: III.

Four of five frequently used orthopedic PROMs possess inadequate content validity: a COSMIN evaluation of the mHHS, HAGOS, IKDC-SKF, KOOS and KNEES-ACL.

PURPOSE: Content validity is the most important property of PROMs. The COSMIN initiative has published guidelines for evaluating the content validity of PROMs, but they have only sparsely been applied to relevant PROMs for musculoskeletal conditions. The aim of this study was to use the COSMIN Risk of Bias checklist to evaluate the content validity of five PROMs, that are highly relevant in musculoskeletal research and used by the arthroscopic surgery community: the modified Harris' Hip Score (mHHS), the Copenhagen Hip and Groin Outcome Score (HAGOS), the International Knee Documentation Committee Subjective Knee evaluation Form (IKDC-SKF), the Knee injury and Osteoarthritis Outcome Score (KOOS) and the Knee Numeric-Entity Evaluation Score ACL (KNEES-ACL). METHODS: The development articles for the five PROMs were identified through searches in PubMed and SCOPUS. A literature search was performed to identify additional studies assessing content validity of the PROMs. Additional information, necessary for the assessments, was obtained from the PROM developers after direct request. To evaluate the quality of the development studies and rate the content validity, the COSMIN Risk of Bias checklist was applied to all studies. RESULTS: All five development studies were identified. Three subsequent content validity studies were identified, all evaluating KOOS and one also IKDC. One content validity study was of inadequate quality and excluded from further analysis. The development of mHHS, IKDC-SKF, and KOOS was rated inadequate and possess insufficient content validity for their target populations. Due to the irrelevance of multiple items, KOOS was in particular inappropriate to evaluate patients with an ACL injury. The development of HAGOS was also rated inadequate, although the insufficiency aspects can be regarded as minor. KNEES-ACL possessed sufficient content validity. CONCLUSION: Out of five PROMs, only KNEES-ACL possessed sufficient content validity. Particularly, KOOS should not be used as an outcome for patients with an ACL injury. There is an urgent need for condition-specific PROMs for musculoskeletal conditions, developed with adequate methods. LEVEL OF EVIDENCE: III.

Patient reported outcome measures for ankle instability. An analysis of 17 existing questionnaires.

BACKGROUND: Patient reported outcome measures (PROMs) are essential for evaluating treatment of ankle instability (AI). The aim was to assess the content validity and the measurement properties of all relevant PROMs for AI. METHODS: Relevant PROMs were identified from PubMed and SCOPUS. The development and validation quality of the PROMs was assessed according to established scientific standards. RESULTS: Seventeen PROMs and 56 validation studies were analyzed. Content validity, which ensures the PROM measures what is relevant, is obtained by involving target patients in the development process. Only three PROMs identified had some degree of patient involvement (Cumberland Ankle Instability Tool (CAIT), Lower Extremity Function Scale (LEFS), and the Foot and Ankle Ability Measure (FAAM)). Of these, only FAAM was somewhat rigorously validated using modern psychometric validation methods, and exhibited superior measurement properties (construct validity). CONCLUSION: No existing PROM is completely adequate to evaluate AI. However, FAAM is the best choice.

Dual-panel translation to Danish and Rasch validation of the Foot and Ankle Ability Measure (FAAM-DK).

BACKGROUND: The Foot and Ankle Ability Measure (FAAM) was developed by involvement of patients with chronic ankle instability (CAI) and has acceptable measurement properties, but is not available in Danish. METHODS: FAAM was translated and culturally adapted into Danish, and its measurement properties were assessed using Rasch analyses. RESULTS: A Danish version was produced with small adaptations, and content relevance was confirmed by Danish patients. The 21-item ADL domain showed misfit to the Rasch model, but after removing six items, the resulting 15-item scale displayed adequate fit. The Sports domain also exhibited misfit, but after removing one item and adjusting due to differential item functioning related to age for another item, a 7-item scale showed good fit. This resulted in a 22-item 2-dimensional Danish version of FAAM. CONCLUSION: The 22-item Danish FAAM exhibits robust measurement properties for patients with various conditions of the lower leg, ankle, and foot, including CAI.

RNA sequencing and immunofluorescence of the myotendinous junction of mature horses and humans.

The myotendinous junction (MTJ) is a specialized interface for transmitting high forces between the muscle and tendon and yet the MTJ is a common site of strain injury with a high recurrence rate. The aim of this study was to identify previously unknown MTJ components in mature animals and humans. Samples were obtained from the superficial digital flexor (SDF) muscle-tendon interface of 20 horses, and the tissue was separated through a sequential cryosectioning approach into muscle, MTJ (muscle tissue enriched in myofiber tips attached to the tendon), and tendon fractions. RT-PCR was performed for genes known to be expressed in the three tissue fractions and t-distributed stochastic neighbor embedding (t-SNE) plots were used to select the muscle, MTJ, and tendon samples from five horses for RNA sequencing. The expression of previously known and unknown genes identified through RNA sequencing was studied by immunofluorescence on human hamstring MTJ tissue. The main finding was that RNA sequencing identified the expression of a panel of 61 genes enriched at the MTJ. Of these, 48 genes were novel for the MTJ and 13 genes had been reported to be associated with the MTJ in earlier studies. The expression of known [COL22A1 (collagen XXII), NCAM (neural cell adhesion molecule), POSTN (periostin), NES (nestin), OSTN (musclin/osteocrin)] and previously undescribed [MNS1 (meiosis-specific nuclear structural protein 1), and LCT (lactase)] MTJ genes was confirmed at the protein level by immunofluorescence on tissue sections of human MTJ. In conclusion, in muscle-tendon interface tissue enriched with myofiber tips, we identified the expression of previously unknown MTJ genes representing diverse biological processes, which may be important in the maintenance of the specialized MTJ.

Collagens in primary frozen shoulder: expression of collagen mRNA isoforms in the different phases of the disease.

OBJECTIVES: Primary frozen shoulder (pFS) has three phases that differ in clinical presentation. It is characterized by contracture of the joint capsule. We hypothesized that there is a general upregulation of collagens in pFS, and that this is highest in the first phase of the disease. The aims of this study were to investigate the expression of various collagens and degradation of collagens in patients with primary pFS and relate this to the three phases of the condition. METHODS: From twenty-six patients with pFS and eight control patients with subacromial impingement, biopsies were obtained during shoulder arthroscopy from the middle glenohumeral ligament and the anterior capsule, and mRNA levels for collagens, MMP-2 and -14 and TGF-ß1, - ß2 and -ß3 in the tissue were analysed using real-time PCR. RESULTS: Genes for collagens type I, III, IV, V, VI and XIV, were activated in pFS, and the total mRNA for all collagens was increased (P < 0.05). This upregulation was independent of disease phases in pFS. In addition, MMP-2, MMP-14, TGF-ß1 and TGF-ß3 were upregulated in all phases of the disease. CONCLUSION: There is a general upregulation and an increased degradation of collagens in pFS in all three phases of the disease. This indicates a constantly increased turnover of the fibrotic tissue in the capsule from pFS. The difference in clinical presentation of pFS observed in the three phases of the disease is not primarily a result of variations in collagen production.