Arthroscopic Partial Meniscectomy for a Degenerative Meniscus Tear Is Not Cost Effective Compared With Placebo Surgery: An Economic Evaluation Based on the FIDELITY Trial Data.

BACKGROUND: In patients with a degenerative tear of the medial meniscus, recent meta-analyses and systematic reviews have shown no treatment benefit of arthroscopic partial meniscectomy (APM) over conservative treatment or placebo surgery. Yet, advocates of APM still argue that APM is cost effective. Giving advocates of APM their due, we note that there is evidence from the treatment of other musculoskeletal complaints to suggest that a treatment may prove cost effective even in the absence of improvements in efficacy outcomes, as it may lead to other benefits, such as diminished productivity loss and reduced costs, and so the question of cost effectiveness needs to be answered for APM. QUESTIONS/PURPOSES: (1) Does APM result in lower postoperative costs compared with placebo surgery? (2) Is APM cost-effective compared with placebo surgery? METHODS: One hundred forty-six adults aged 35 to 65 years with knee symptoms consistent with a degenerative medial meniscus tear and no knee osteoarthritis according to the American College of Rheumatology clinical criteria were randomized to APM (n = 70) or placebo surgery (n = 76). In the APM and placebo surgery groups, mean age was 52 ± 7 years and 52 ± 7 years, and 60% (42 of 70) and 62% (47 of 76) of participants were men, respectively. There were no between-group differences in baseline characteristics. In both groups, a standard diagnostic arthroscopy was first performed. Thereafter, in the APM group, the torn meniscus was trimmed to solid meniscus tissue, whereas in the placebo surgery group, APM was carefully mimicked but no resection of meniscal tissue was performed; as such, surgical costs were the same in both arms and were not included in the analyses. All patients received identical postoperative care including a graduated home-based exercise program. At the 2-year follow-up, two patients were lost to follow-up, both in the placebo surgery group. Cost effectiveness over the 2-year trial period was computed as incremental net monetary benefit (INMB) for improvements in quality-adjusted life years (QALY), using both the societal (primary) and healthcare system (secondary) perspectives. To be able to consider APM cost effective, the CEA analysis should yield a positive INMB value. Nonparametric bootstrapping was used to assess uncertainty. Several one-way sensitivity analyses were also performed. RESULTS: APM did not deliver lower postoperative costs, nor did it convincingly improve quality of life scores when compared with placebo surgery. From a societal perspective, APM was associated with € 971 (95% CI -2013 to 4017) higher costs and 0.015 (95% CI -0.011 to 0.041) improved QALYs over 2-year follow-up compared with placebo surgery. Both differences were statistically inconclusive (a wide 95% CI that crossed the line of no difference). Using the conventional willingness to pay (WTP) threshold of € 35,000 per QALY, APM resulted in a negative INMB of € -460 (95% CI -3757 to 2698). In our analysis, APM would result in a positive INMB only when the WTP threshold rises to about € 65,000 per QALY. The wide 95% CIs suggests uncertain cost effectiveness irrespective of chosen WTP threshold. CONCLUSION: The results of this study lend further support to clinical practice guidelines recommending against the use of APM in patients with a degenerative meniscus tear. Given the robustness of existing evidence demonstrating no benefit or cost effectiveness of APM over nonsurgical treatment or placebo surgery, future research is unlikely to alter this conclusion.Level of Evidence Level III, economic analysis.

Hyaluronic Acid and Large Extracellular Vesicles (EVs) in Synovial Fluid and Plasma of Patients With End-Stage Arthritis: Positive Association of EVs to Joint Pain.

OBJECTIVE: Hyaluronic acid (HA) in synovial fluid (SF) contributes to boundary lubrication with altered levels in osteoarthritis (OA) and rheumatoid arthritis (RA). SF extracellular vesicles (EVs) may participate in arthritis by affecting inflammation and cartilage degradation. It remains unknown whether HA and EVs display joint-specific alterations in arthritic SFs. DESIGN: We investigated the numbers and characteristics of HA-particles and large EVs in SF from knees and shoulders of 8 OA and 8 RA patients and 8 trauma controls, and in plasma from 10 healthy controls and 11 knee OA patients. The plasma and SF HA concentrations were determined with a sandwich-type enzyme-linked sorbent assay, and EVs and HA-particles were characterized from plasma and unprocessed and centrifuged SFs with confocal microscopy. The data were compared according to diagnosis, location, and preanalytical processing. RESULTS: The main findings were: (1) OA and RA SFs can be distinguished from trauma joints based on the distinctive profiles of HA-particles and large EVs, (2) there are differences in the SF HA and EV characteristics between shoulder and knee joints that could reflect their dissimilar mobility, weight-bearing, and shock absorption properties, (3) EV counts in SF and plasma can positively associate with pain parameters independent of age and body adiposity, and (4) low-speed centrifugation causes alterations in the features of HA-particles and EVs, complicating their examination in the original state. CONCLUSIONS: Arthritis and anatomical location can affect the characteristics of HA-particles and large EVs that may have potential as biomarkers and effectors in joint degradation and pain.

Clinical Super-Resolution Computed Tomography of Bone Microstructure: Application in Musculoskeletal and Dental Imaging.

PURPOSE: Clinical cone-beam computed tomography (CBCT) devices are limited to imaging features of half a millimeter in size and cannot quantify the tissue microstructure. We demonstrate a robust deep-learning method for enhancing clinical CT images, only requiring a limited set of easy-to-acquire training data. METHODS: Knee tissue from five cadavers and six total knee replacement patients, and 14 teeth from eight patients were scanned using laboratory CT as training data for the developed super-resolution (SR) technique. The method was benchmarked against ex vivo test set, 52 osteochondral samples are imaged with clinical and laboratory CT. A quality assurance phantom was imaged with clinical CT to quantify the technical image quality. To visually assess the clinical image quality, musculoskeletal and maxillofacial CBCT studies were enhanced with SR and contrasted to interpolated images. A dental radiologist and surgeon reviewed the maxillofacial images. RESULTS: The SR models predicted the bone morphological parameters on the ex vivo test set more accurately than conventional image processing. The phantom analysis confirmed higher spatial resolution on the SR images than interpolation, but image grayscales were modified. Musculoskeletal and maxillofacial CBCT images showed more details on SR than interpolation; however, artifacts were observed near the crown of the teeth. The readers assessed mediocre overall scores for both SR and interpolation. The source code and pretrained networks are publicly available. CONCLUSION: Model training with laboratory modalities could push the resolution limit beyond state-of-the-art clinical musculoskeletal and dental CBCT. A larger maxillofacial training dataset is recommended for dental applications.

Near-Infrared Spectroscopy Enables Arthroscopic Histologic Grading of Human Knee Articular Cartilage.

Purpose: To develop the means to estimate cartilage histologic grades and proteoglycan content in ex vivo arthroscopy using near-infrared spectroscopy (NIRS). Methods: In this experimental study, arthroscopic NIR spectral measurements were performed on both knees of 9 human cadavers, followed by osteochondral block extraction and in vitro measurements: reacquisition of spectra and reference measurements (proteoglycan content, and three histologic scores). A hybrid model, combining principal component analysis and linear mixed-effects model (PCA-LME), was trained for each reference to investigate its relationship with in vitro NIR spectra. The performance of the PCA-LME model was validated with ex vivo spectra before and after the exclusion of outlying spectra. Model performance was evaluated based on Spearman rank correlation (ρ) and root-mean-square error (RMSE). Results: The PCA-LME models performed well (independent test: average ρ = 0.668, RMSE = 0.892, P < .001) in the prediction of the reference measurements based on in vitro data. The performance on ex vivo arthroscopic data was poorer but improved substantially after outlier exclusion (independent test: average ρ = 0.462 to 0.614, RMSE = 1.078 to 0.950, P = .019 to .008). Conclusions: NIRS is capable of nondestructive evaluation of cartilage integrity (i.e., histologic scores and proteoglycan content) under similar conditions as in clinical arthroscopy. Clinical Relevance: There are clear clinical benefits to the accurate assessment of cartilage lesions in arthroscopy. Visual grading is the current standard of care. However, optical techniques, such as NIRS, may provide a more objective assessment of cartilage damage.

Survival and failure analysis of 167 medial opening wedge high tibial osteotomy with a locking titanium plate.

INTRODUCTION: This retrospective study investigated the survival rate and complications of medial opening wedge high tibial osteotomy (MOWHTO) with a precountered titanium locking plate. HYPOTHESIS: Advanced age (≥50years), gender, body mass index (BMI), type of osteotomy cut (monoplanar or biplanar), osteoarthritis (OA) grade, the use of bone grafting or substitution and preoperative hip-knee-ankle (HKA) have impact on MOWHTO survival. MATERIAL AND METHODS: A total of 167 knees (155 patients) were consecutively operated during the study period of 01.01.2006-31.12.2014. The primary outcome measure was survival without a need for revision to total knee arthroplasty (TKA). The secondary outcome was a major adverse event leading to revision surgery. Adverse events and complications were evaluated and radiological analyses were done. Furthermore, risk factors that affected the survival were analysed with the Cox regression model. RESULTS: The mean follow-up time was 7.7 (SD: 2.7, range: 0.9-14.5) years. The Kaplan-Meier estimates for the cumulative survival considering no need for TKA after MOWHTO was 90% at 5years, 78% at 10years and 61% at 14.5years (SE: 0.4, 95% CI: 11.2-12.9). The adverse event rate was 30% and 35% of the patients required a secondary surgery. The Cox regression model did not show that age, gender, weight, osteotomy type, the use of bone grafting or substitution, preoperative HKA angle or OA grade were not risk factors for conversion to arthroplasty. DISCUSSION: MOWHTO with locking plate provides good survival with no need for TKA in 78% of the knee medial OA patients at 10years of cumulative follow-up. However, a high adverse event rate (30%) is expected. Risk factors for conversion to TKA were not found and thereby hypothesis of this study was not proved. LEVEL OF EVIDENCE: VI; Retrospective cohort study.

Metabolomics of Synovial Fluid and Infrapatellar Fat Pad in Patients with Osteoarthritis or Rheumatoid Arthritis.

Osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA) are inflammatory joint diseases with complex and insufficiently understood pathogeneses. Our objective was to characterize the metabolic fingerprints of synovial fluid (SF) and its adjacent infrapatellar fat pad (IFP) obtained during the same surgical operation from OA and RA knees. Non-targeted metabolite profiling was performed for 5 non-inflammatory trauma controls, 10 primary OA (pOA) patients, and 10 seropositive RA patients with high-resolution mass spectrometry-based techniques, and metabolites were matched with known metabolite identities. Groupwise differences in metabolic features were analyzed with the univariate Welch's t-test and the multivariate linear discriminant analysis (LDA) and principal component analysis (PCA). Significant discrimination of metabolite profiles was discovered by LDA for both SF and IFP and by PCA for SF based on diagnosis. In addition to a few drug-derived substances, there were 16 and 13 identified metabolites with significant differences between the diagnoses in SF and IFP, respectively. The pathways downregulated in RA included androgen, bile acid, amino acid, and histamine metabolism, and those upregulated included biotin metabolism in pOA and purine metabolism in RA and pOA. The RA-induced downregulation of androgen and bile acid metabolism was observed for both SF and IFP. The levels of 11 lipid metabolites, mostly glycerophospholipids and fatty acid amides, were also altered by these inflammatory conditions. The identified metabolic pathways could be utilized in the future to deepen our understanding of the pathogeneses of OA and RA and to develop not only biomarkers for their early diagnosis but also therapeutic targets.

Arthroscopic Bankart versus open Latarjet as a primary operative treatment for traumatic anteroinferior instability in young males: a randomised controlled trial with 2-year follow-up.

OBJECTIVES: To compare the success rates of arthroscopic Bankart and open Latarjet procedure in the treatment of traumatic shoulder instability in young males. DESIGN: Multicentre randomised controlled trial. SETTING: Orthopaedic departments in eight public hospitals in Finland. PARTICIPANTS: 122 young males, mean age 21 years (range 16-25 years) with traumatic shoulder anteroinferior instability were randomised. INTERVENTIONS: Arthroscopic Bankart (group B) or open Latarjet (group L) procedure. MAIN OUTCOME MEASURES: The primary outcome measure was the reported recurrence of instability, that is, dislocation at 2-year follow-up. The secondary outcome measures included clinical apprehension, sports activity level, the Western Ontario Shoulder Instability Index, the pain Visual Analogue Scale, the Oxford Shoulder Instability Score, the Constant Score and the Subjective Shoulder Value scores and the progression of osteoarthritic changes in plain films and MRI. RESULTS: 91 patients were available for analyses at 2-year follow-up (drop-out rate 25%). There were 10 (21%) patients with redislocations in group B and 1 (2%) in group L, p=0.006. One (9%) patient in group B and five (56%) patients in group L returned to their previous top level of competitive sports (p=0.004) at follow-up. There was no statistically significant between group differences in any of the other secondary outcome measures. CONCLUSIONS: Arthroscopic Bankart operation carries a significant risk for short-term postoperative redislocations compared with open Latarjet operation, in the treatment of traumatic anteroinferior instability in young males. Patients should be counselled accordingly before deciding the surgical treatment. TRIAL REGISTRATION NUMBER: NCT01998048.

Long-term follow-up results of medial opening wedge high tibia osteotomy with a pre-countered non-locking steel plate.

INTRODUCTION: This retrospective study investigated the long-term follow-up results of medial opening wedge high tibial osteotomy (MOWHTO) with a pre-countered non-locking steel plate implant (Puddu plate = PP) used for medial knee osteoarthrosis (OA) treatment. MATERIALS AND METHODS: Consecutive 70 MOWHTOs (66 patients) were performed between 01.01.2004 and 31.12.2008 with the mean follow-up time of 11.4 (SD 4.5; range 1.2-16.1) years. The Kaplan-Meier survival analysis was used to evaluate the cumulative survival of the implant in terms of age (< 50 years old and ≥ 50 years old) and gender. Adverse events were studied and Cox regression analysis was used to evaluate risk factors [age, gender, body mass index (BMI), preoperative mechanical axis, severity of OA, use of bone grafting or substitution and undercorrection of mechanical axis from varus to valgus] for revisions. RESULTS: The estimates for the cumulative survival with no need for TKA after MOWHTO were 86% at 5 years, 67% at 10 years and 58% at 16.1 years (SE 0.6, CI 95% 11.1-13.5). A total of 33/70 (47%) adverse events occurred and 38/70 (54%) knees required some revision surgery during the follow-up. Cox regression did not show any statistically significant risk factors for revision. CONCLUSIONS: The PP has feasible MOWHTO results with a cumulative survival of 67% at 10 years with no need for conversion to TKA. Many adverse events occurred and revision rate due to any reason was high. Age or gender did not have statistically significant differences in terms of survival.

High-resolution infrared microspectroscopic characterization of cartilage cell microenvironment.

The lateral resolution of infrared spectroscopy has been inadequate for accurate biochemical characterization of the cell microenvironment, a region regulating biochemical and biomechanical signals to cells. In this study, we demonstrate the capacity of a high-resolution Fourier transform infrared microspectroscopy (HR-FTIR-MS) to characterize the collagen content of this region. Specifically, we focus on the collagen content in the cartilage cell (chondrocyte) microenvironment of healthy and osteoarthritic (OA) cartilage. Human tibial cartilage samples (N = 28) were harvested from 7 cadaveric donors and graded for OA severity (healthy, early OA, advanced OA). HR-FTIR-MS was used to analyze the collagen content of the chondrocyte microenvironment of five distinct zones across the tissue depth. HR-FTIR-MS successfully showed collagen content distribution across chondrocytes and their environment. In zones 2 and 3 (10 - 50% of the tissue thickness), we observed that collagen content was smaller (P < 0.05) in early OA compared to the healthy tissue in the vicinity of cells (pericellular region). The collagen content loss was extended to the extracellular matrix in advanced OA tissue. No significant differences in the collagen content of the chondrocyte microenvironment were observed between the groups in the most superficial (0-10%) and deep zones (50-100%). HR-FTIR-MS revealed collagen loss in the early OA cartilage pericellular region before detectable changes in the extracellular matrix in advanced OA. HR-FTIR-MS-based compositional assessment enables a better understanding of OA-related changes in tissues. This technique can be used to identify new disease mechanisms enabling better intervention strategies. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) is the most common degenerative joint disease causing pain and disability. While significant progress has been made in OA research, OA pathogenesis is still poorly understood and current OA treatments are mainly palliative. This study demonstrates that high-resolution FTIR microspectroscopy (HR-FTIR-MS) can characterize OA-induced compositional changes in the cell microenvironment (pericellular matrix) during the early disease stages before tissue changes in the extracellular matrix become apparent. This technique may further enable the identification of new OA mechanisms and improve our current understanding of OA pathogenesis, thus, enabling the development of better treatment methods.

Synovial Fluid Fatty Acid Profiles Are Differently Altered by Inflammatory Joint Pathologies in the Shoulder and Knee Joints.

Anomalies of fatty acid (FA) metabolism characterize osteoarthritis (OA) and rheumatoid arthritis (RA) in the knee joint. No previous study has investigated the synovial fluid (SF) FA manifestations in these aging-related inflammatory diseases in the shoulder. The present experiment compared the FA alterations between the shoulder and knee joints in patients with end-stage OA or end-stage RA. SF samples were collected during glenohumeral or knee joint surgery from trauma controls and from OA and RA patients (n = 42). The FA composition of SF total lipids was analyzed by gas chromatography with flame ionization and mass spectrometric detection and compared across cohorts. The FA signatures of trauma controls were mostly uniform in both anatomical locations. RA shoulders were characterized by elevated percentages of 20:4n-6 and 22:6n-3 and with reduced proportions of 18:1n-9. The FA profiles of OA and RA knees were relatively uniform and displayed lower proportions of 18:2n-6, 22:6n-3 and total n-6 polyunsaturated FAs (PUFAs). The results indicate location- and disease-dependent differences in the SF FA composition. These alterations in FA profiles and their potential implications for the production of PUFA-derived lipid mediators may affect joint lubrication, synovial inflammation and pannus formation as well as cartilage and bone degradation and contribute to the pathogeneses of inflammatory joint diseases.

Midterm follow-up results of two different types of implants in opening wedge high tibia osteotomy.

BACKGROUND: This retrospective study investigated the midterm results of medial opening wedge high tibia osteotomy, with a monoplanar or a biplanar osteotomy using two types of implant system. METHODS: Osteotomies were performed on 241 knees (231 patients). The mean follow-up period was 6.0 years (SD 3.0, range 0.2-12.8 years). Two types of implant system were used, a precountered non-locking plate (PP) (n = 74) and a precountered locking plate (LP) (n = 167). A Kaplan-Meier cumulative survival curve and a Cox regression model were used to analyse and revise survival and risk factors. RESULTS: Cumulative survival estimates for LP were 80% at 5 years, and 64% at 10 years (SE = 0.4, CI 95%: 9.0-10.5), and for PP, they were 68% at 5 years and 49% at 10 years (SE = 0.5, CI: 95% 6.3-8.2) (p = 0.024). The revision rate was 26% (44/167) for the LP group, and 47% (35/74) for the PP group (p = 0.001). Reoperations on LP osteotomies occurred for the tibial monoplanar cut and biplanar cut groups, in 19/52 (37%) and 25/167 (16%) osteotomies, respectively (p = 0.04). Our Cox regression model showed that PP had a higher risks (RR = 1.7; CI: 95% 1.1-2.6) of revision, when compared with LP (p = 0.026). CONCLUSIONS: The risk of revision for any reason and that of early conversion to total knee arthroplasty (TKA) after high tibia osteotomy were significantly increased for PP, when compared with LP.

Anterior glenohumeral instability treated with arthroscopic Bankart operation - a retrospective 5-year follow-up study.

BACKGROUND: This retrospective study investigated 5-year results of primary arthroscopic operation for anterior glenohumeral instability (AI) with special interest in patients aged<25 years and gender. HYPOTHESIS: Recurrence of AI is higher in male patients aged<25 years than older patients or females. PATIENTS AND METHODS: Primary arthroscopic Bankart repair was performed between January 2009 and December 2015 on 156 shoulders [154 patients, 104/156 (67%) males]. The mean follow-up was 5.6 (SD 2.1, range 0.4-8.9) years. Outcome measures, including re-dislocation, fear of dislocation, Western Ontario instability index, Subjective shoulder value and pain Numerical rating scale scores, the number of revision surgeries and satisfaction with the result of surgical treatment, were assessed for 130 shoulders [82/130 (63%) males]. AI recurrence was defined as a dislocation or a fear of such. RESULTS: The Kaplan-Meier analysis estimates for the cumulative survival of stable shoulders were 28% at 8.8 years for patients aged<25 years (SE 0.4, CI 95% 5.5-7.2) and 53% at 8.9 years for patients aged ≥25 years (SE 0.2, CI 95% 7.2-8.0; p=0.005). The Kaplan-Meier estimates for the cumulative survival of stable shoulders were 50% at 8.9 years for males (SE 0.3, CI 95% 6.8-7.8) and 37% at 8.6 years for females (SE 0.3, CI 95% 6.5-7.7; p=0.8). Mean time to revision was 2.4 (SD 1.7, range 0.4-5.3) years. DISCUSSION: Recurrence of AI was higher in the patients aged<25 years (p=0.005), but gender was not a risk factor. Re-operation rate due to recurrent AI was 10% in this 5-year follow-up. LEVEL OF EVIDENCE: III; case-control study.

Operative versus conservative treatment of small, nontraumatic supraspinatus tears in patients older than 55 years: over 5-year follow-up of a randomized controlled trial.

BACKGROUND: Nontraumatic rotator cuff tear is a common shoulder problem that can be treated either conservatively or operatively. In the previous publications of the 1- and 2-year results of this trial, we found no significant between-group clinical differences. The aim of this study was to investigate the differences in mid-term clinical and radiologic outcomes in patients older than 55 years. MATERIALS AND METHODS: One hundred eighty shoulders with symptomatic, nontraumatic supraspinatus tears were randomly assigned to 1 of the 3 cumulatively designed treatment groups: physiotherapy (group 1); acromioplasty and physiotherapy (group 2); and rotator cuff repair, acromioplasty, and physiotherapy (group 3). The change in the Constant score was the primary outcome measure. The secondary outcome measures were the change in the visual analog scale score for pain and patient satisfaction. Radiologic analysis included evaluation of glenohumeral osteoarthritis (OA) and rotator cuff tear arthropathy (CTA). RESULTS: A total of 150 shoulders (mean age, 71 years) were available for analysis after a mean follow-up period of 6.2 years. The mean sagittal tear size of the supraspinatus tendon tear at baseline was 10 mm in all groups (P = .33). During follow-up, 8 shoulders in group 1 and 2 shoulders in group 2 crossed over to rotator cuff repair. The mean baseline Constant score was 57.1, 58.2, and 58.7 in groups 1, 2, and 3, respectively (P = .85). There were no significant differences (P = .84) in the mean change in the Constant score: 18.5 in group 1, 17.9 in group 2, and 20.0 in group 3. There were no statistically significant differences in the change in the visual analog scale pain score (P = .74) and patient satisfaction (P = .83). At follow-up, there were no statistically significant differences in the mean progression of glenohumeral OA (P = .538) or CTA (P = .485) among the groups. However, the mean progression of glenohumeral OA from baseline to follow-up was statistically significant in the trial population (P = .0045). CONCLUSIONS: On the basis of this study, operative treatment is no better than conservative treatment regarding small, nontraumatic, single-tendon supraspinatus tears in patients older than 55 years. Operative treatment does not protect against degeneration of the glenohumeral joint or CTA. Conservative treatment is a reasonable option for the primary initial treatment of these tears.

Characterization of hyaluronan-coated extracellular vesicles in synovial fluid of patients with osteoarthritis and rheumatoid arthritis.

BACKGROUND: Hyaluronic acid (HA) is the major extracellular matrix glycosaminoglycan with a reduced synovial fluid (SF) concentration in arthropathies. Cell-derived extracellular vesicles (EV) have also been proposed to contribute to pathogenesis in joint diseases. It has recently been shown that human SF contains HA-coated EV (HA-EV), but their concentration and function in joint pathologies remain unknown. METHODS: The aim of the present study was to develop an applicable method based on confocal laser scanning microscopy (CLSM) and image analysis for the quantification of EV, HA-particles, and HA-EV in the SF of the human knee joint. Samples were collected during total knee replacement surgery from patients with end-stage rheumatoid arthritis (RA, n = 8) and osteoarthritis (OA, n = 8), or during diagnostic/therapeutic arthroscopy unrelated to OA/RA (control, n = 7). To characterize and quantify EV, HA-particles, and HA-EV, SF was double-stained with plasma membrane and HA probes and visualized by CLSM. Comparisons between the patient groups were performed with the Kruskal-Wallis analysis of variance. RESULTS: The size distribution of EV and HA-particles was mostly similar in the study groups. Approximately 66% of EV fluorescence was co-localized with HA verifying that a significant proportion of EV carry HA. The study groups were clearly separated by the discriminant analysis based on the CLSM data. The intensities of EV and HA-particle fluorescences were lower in the RA than in the control and OA groups. CONCLUSIONS: CLSM analysis offers a useful tool to assess HA-EV in SF samples. The altered EV and HA intensities in the RA SF could have possible implications for diagnostics and therapy.

Near-Infrared Spectroscopy for Mapping of Human Meniscus Biochemical Constituents.

Degenerative changes in meniscus are diagnosed during surgery by means of mechanical testing and visual evaluation. This method is qualitative and highly subjective, providing very little information on the internal state of the meniscus. Thus, there is need for novel quantitative methods that can support decision-making during arthroscopic surgery. In this study, we investigate the potential of near-infrared spectroscopy (NIRS) for mapping the biochemical constituents of human meniscus, including water, uronic acid, and hydroxyproline contents. Partial least squares regression models were developed using data from 115 measurement locations of menisci samples extracted from 7 cadavers and 11 surgery patient donors. Model performance was evaluated using an independent test set consisting of 55 measurement locations within a meniscus sample obtained from a separate cadaver. The correlation coefficient of calibration (ρtraining), test set (ρtest), and root-mean-squared error of test set (RMSEP) were as follows: water (ρtraining = 0.61, ρtest = 0.39, and RMSEP = 2.27 percentage points), uronic acid (ρtraining = 0.68, ρtest = 0.69, and RMSEP = 6.09 basis points), and hydroxyproline (ρtraining = 0.84, ρtest = 0.58, and error = 0.54 percentage points). In conclusion, the results suggest that NIRS could enable rapid arthroscopic mapping of changes in meniscus biochemical constituents, thus providing means for quantitative assessment of meniscus degeneration.

Trends of shoulder instability surgery in Finland: a nationwide register study.

OBJECTIVE: Rate of shoulder instability surgery (SIS) has increased in different specific populations. We analysed nationwide trend of SIS in adults in Finland between 1997 and 2014. DESIGN: A retrospective register study. SETTING: National Hospital Discharge Register of Finland. PARTICIPANTS: A total of 22 550 adult patients with SIS in Finland (1997-2014). PRIMARY AND SECONDARY OUTCOME MEASURES: Analysis included appropriate diagnosis (International Classification of Diseases 10) and procedure coding combinations applicable for SIS. The primary outcome variable was the incidence of SIS per 100 000 person-years, and the secondary outcomes were the study year, sex, age groups (18-29, 30-49 and over 50 years of age) and the type of hospital (public or private). RESULTS: The overall nationwide rate of SIS in adults increased 177% between 1997 and 2014 in Finland. The rate was the lowest (13/100 000 person-years) in 1997, and the peak rate (40/100 000 person-years) was noted in 2007. The increase in rate was rapid between 1997 and 2007, after which the rate became stable. During the study period, the highest increases were noted in the young adults age group (270%), and especially in the middle-aged group who were operated on in private hospitals (930%). CONCLUSIONS: The rate of SIS increased almost threefold in Finland from 1997 to 2014. The increase was most significant in young and middle-aged adults (18-50 years), in men, and in private hospitals.

Arthroscopic partial meniscectomy for a degenerative meniscus tear: a 5 year follow-up of the placebo-surgery controlled FIDELITY (Finnish Degenerative Meniscus Lesion Study) trial.

OBJECTIVES: To assess the long-term effects of arthroscopic partial meniscectomy (APM) on the development of radiographic knee osteoarthritis, and on knee symptoms and function, at 5 years follow-up. DESIGN: Multicentre, randomised, participant- and outcome assessor-blinded, placebo-surgery controlled trial. SETTING: Orthopaedic departments in five public hospitals in Finland. PARTICIPANTS: 146 adults, mean age 52 years (range 35-65 years), with knee symptoms consistent with degenerative medial meniscus tear verified by MRI scan and arthroscopically, and no clinical signs of knee osteoarthritis were randomised. INTERVENTIONS: APM or placebo surgery (diagnostic knee arthroscopy). MAIN OUTCOME MEASURES: We used two indices of radiographic knee osteoarthritis (increase in Kellgren and Lawrence grade ≥1, and increase in Osteoarthritis Research Society International (OARSI) atlas radiographic joint space narrowing and osteophyte sum score, respectively), and three validated patient-relevant measures of knee symptoms and function (Western Ontario Meniscal Evaluation Tool (WOMET), Lysholm, and knee pain after exercise using a numerical rating scale). RESULTS: There was a consistent, slightly greater risk for progression of radiographic knee osteoarthritis in the APM group as compared with the placebo surgery group (adjusted absolute risk difference in increase in Kellgren-Lawrence grade ≥1 of 13%, 95% CI -2% to 28%; adjusted absolute mean difference in OARSI sum score 0.7, 95% CI 0.1 to 1.3). There were no relevant between-group differences in the three patient-reported outcomes: adjusted absolute mean differences (APM vs placebo surgery), -1.7 (95% CI -7.7 to 4.3) in WOMET, -2.1 (95% CI -6.8 to 2.6) in Lysholm knee score, and -0.04 (95% CI -0.81 to 0.72) in knee pain after exercise, respectively. The corresponding adjusted absolute risk difference in the presence of mechanical symptoms was 18% (95% CI 5% to 31%); there were more symptoms reported in the APM group. All other secondary outcomes comparisons were similar. CONCLUSIONS: APM was associated with a slightly increased risk of developing radiographic knee osteoarthritis and no concomitant benefit in patient-relevant outcomes, at 5 years after surgery. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01052233 and NCT00549172).

Structure-Function Relationships of Healthy and Osteoarthritic Human Tibial Cartilage: Experimental and Numerical Investigation.

Relationships between composition, structure and constituent-specific functional properties of human articular cartilage at different stages of osteoarthritis (OA) are poorly known. We established these relationships by comparison of elastic, viscoelastic and fibril-reinforced poroelastic mechanical properties with microscopic and spectroscopic analysis of structure and composition of healthy and osteoarthritic human tibial cartilage (n = 27). At a low frequency (0.005 Hz), proteoglycan content correlated negatively and collagen content correlated positively with the phase difference (i.e. tissue viscosity). At a high-frequency regime (> 0.05 Hz), proteoglycan content correlated negatively and collagen orientation angle correlated positively with the phase difference. Proteoglycans were lost in the early and advanced OA groups compared to the healthy group, while the superficial collagen orientation angle was greater only in the advanced OA group compared to the healthy group. Simultaneously, the initial fibril network modulus (fibril pretension) was smaller in the early and advanced OA groups compared to the healthy group. These findings suggest different mechanisms contribute to cartilage viscosity in low and high frequencies, and that the loss of superficial collagen pretension during early OA is due to lower tissue swelling (PG loss), while in advanced OA, both collagen disorganization and lower swelling modulate the collagen fibril pretension.