Kellgren-Lawrence Grade Research Articles

Improving Accuracy and Reproducibility of Cartilage T2 Mapping in the OAI Dataset Through Extended Phase Graph Modeling.

The Osteoarthritis Initiative (OAI) collected extensive imaging data, including Multi-Echo Spin-Echo (MESE) sequences for measuring knee cartilage T2 relaxation times. Mono-exponential models are used in the OAI for T2 fitting, which neglects stimulated echoes and B1 inhomogeneities. Extended Phase Graph (EPG) modeling addresses these limitations but has not been applied to the OAI dataset. To assess how different fitting methods, including EPG-based and exponential-based approaches, affect the accuracy and reproducibility of cartilage T2 in the OAI dataset. Retrospective. From OAI dataset, 50 subjects, stratified by osteoarthritis (OA) severity using Kellgren-Lawrence grades (KLG), and 50 subjects without OA diagnosis during OAI duration were selected (each group: 25 females, mean ages ~61 years). 3-T, two-dimensional (2D) MESE sequence. Femoral and tibial cartilages were segmented from DESS images, subdivided into seven sub-regions, and co-registered to MESE. T2 maps were obtained using three EPG-based methods (nonlinear least squares, dictionary matching, and deep learning) and three mono-exponential approaches (linear least squares, nonlinear least squares, and noise-corrected exponential). Average T2 values within sub-regions were obtained. Pair-wise agreement among fitting methods was evaluated using the stratified subjects, while reproducibility using healthy subjects. Each method's T2 accuracy and repeatability varying signal-to-noise ratio (SNR) were assessed with simulations. Bland-Altman analysis, Lin's concordance coefficient, and coefficient of variation assessed agreement, repeatability, and reproducibility. Statistical significance was set at P-value <0.05. EPG-based methods demonstrated superior T2 accuracy (mean absolute error below 0.5 msec at SNR > 100) compared to mono-exponential methods (error > 7 msec). EPG-based approaches had better reproducibility, with limits of agreement 1.5-5 msec narrower than exponential-based methods. T2 values from EPG methods were systematically 10-17 msec lower than those from mono-exponential fitting. EPG modeling improved agreement and reproducibility of cartilage T2 mapping in subjects from the OAI dataset. 3 TECHNICAL EFFICACY: Stage 1.

Association of MRI-based knee osteoarthritis structural phenotypes with short-term structural progression and subsequent total knee replacement

BackgroundThe failure of disease-modifying osteoarthritis drugs (DMOADs) trials lies mainly in the heterogeneity of the disease, which calls for a more precise population with specific progression and outcomes. This study aimed to determine whether and which MRI-based structural phenotype of knee osteoarthritis (KOA) is associated with short-term structural progression and subsequent total knee replacement (TKR).MethodsA longitudinal study was conducted among participants with baseline Kellgren-Lawrence grade (KLG) ≥ 2 from the Osteoarthritis Initiative (OAI). The structural phenotypes at baseline were defined as subchondral bone, meniscus/cartilage and inflammatory phenotypes according to the MRI Osteoarthritis Knee Score (MOAKS). The primary outcome was the progression of structural abnormalities within 24 months and multivariable logistic regressions were applied to evaluate the associations. The secondary outcome was the incidence of TKR during 108 months. Cox regressions and Kaplan–Meier survival curves were used for the analysis.ResultsA total of 733 participants with KOA were finally included in our study, with 493 (67.3%) having the three main structural phenotypes. For the primary outcome, the subchondral bone phenotype (OR [95% CI]:1.71 [1.02, 2.83], 1.52 [1.06, 2.18], 1.65 [1.11, 2.42], respectively) and the inflammatory phenotype (OR [95% CI]: 1.69 [1.05, 2.74], 1.82 [1.31, 2.52], 2.15 [1.48, 3.14], respectively) were both associated with the short-term progression of joint space narrowing, osteophytes and sclerosis in 24 months, whereas the meniscus/cartilage phenotype was only associated with the progression of osteophytes and sclerosis. For the secondary outcome, the subchondral bone phenotype (HR [95% CI]: 1.71 [1.06–2.78]) and inflammatory phenotype (HR [95%CI]: 2.00 [1.02–2.67]) were associated with shorter time to subsequent TKR, but not the meniscus/cartilage phenotype. Besides, the cumulative effect when the structural phenotype overlapped was confirmed in both outcomes.ConclusionsThe subchondral bone phenotype and inflammatory phenotype were associated with the progression of joint space narrowing, osteophytes and sclerosis in 24 months, along with subsequent TKR in 108 months. Besides, additive effects of overlapped phenotypes were further determined. These phenotypes could serve as valuable screening tools for future clinical trials and provide guidance for risk evaluation.

Corrective Intra-articular Osteotomy for Malreductions of Tibial Pilon Fractures in Patients Less Than 55 Years Old.

Tibial pilon malreductions are challenging to correctively reconstruct, and the relevant literature is limited. This study aims to assess whether corrective intra-articular osteotomy is worthwhile to treat relatively younger (<55-year-old) patients with intra-articular malreductions of pilon fractures. This is a retrospective observational study with a minimum follow-up of 2 years. From 2013 to 2021, 21 patients (mean age: 39.2 ± 11.2 years) with intra-articular pilon malreductions ≥6 weeks treated with intra-articular osteotomies were analyzed. The median interval time until intra-articular osteotomy was 76 (interquartile range [IQR], 49-149) days. Plain radiographs and computed tomography were used for radiographic assessments. Clinical outcomes were evaluated with visual analog scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, the 36-Item Short-Form Health Survey (SF-36) score, and ankle range of motion (ROM). The median follow-up duration was 34.6 (IQR, 26.1-74.3) months. The median articular displacement was reduced from 12.7 mm preoperatively to 2.7 mm postoperatively (P < .05). According to the Kellgren-Lawrence grading, 16 patients were assigned to stage II, 4 to stage III, and 1 to stage IV. In the 10 patients with available preoperative assessments, substantial improvement was found in the VAS score, from 5.90 to 2.0 at the final follow-up (P < .05). Similarly, the AOFAS ankle-hindfoot score and SF-36 scores improved (P < .05). Ankle ROM did not change a clinically meaningful amount. Progressive degenerative changes were noted in 2 of 10 patients who had adequate preoperative imaging. Four patients had VAS scores ≥4 including 1 patient who is scheduled for an arthrodesis. In this small series, we found that the corrective osteotomies generally provided reasonable improvement at 3 years in patients <55 years old with intra-articular malreduction of pilon fractures. Prospective cohort studies are needed to determine if it is worthwhile in long-term outcome.

Osteochondral Autograft Transplantation for Symptomatic Full-thickness Patellar Cartilage Defects in Adolescents.

This study aimed to review the clinical, radiographic, and magnetic resonance imaging (MRI) outcomes of osteochondral autograft transplantation applied to patellar cartilage lesions of patients under 18 years of age. Data from nine consecutive patients were retrospectively analyzed for indications, preoperative complications, and clinical-radiographic outcomes. Patients were clinically evaluated using the Pedi-IKDC and Lysholm scores. In addition, return to sports and knee pain were assessed. MRI evaluation included an analysis of osteochondral graft integration using the magnetic resonance observation of cartilage repair tissue 2.0 score and radiographic classification of osteoarthritis using the Kellgren-Lawrence system. Nine patients (9 knees, 6 males) with a mean age of 14 years (SD: 1.7, range; 11 to 17y) were analyzed. Lesions were located on the medial facet (N=5), lateral facet (N=3), and central ridge of the patella (N=1). One or 2 cylindrical osteochondral grafts were transplanted, with a median diameter of 9mm (range: 8 to 10mm). The average lesion size was 102.9mm2. At a mean follow-up of 45.1 months (range: 23 to 117mo), the mean Pedi-IKDC score was 89.2 (SD: 9.8), and the Lysholm score was 94.4 (SD: 4.8). Patients returned to sports in an average of 7.3 months (SD: 2, range: 6 to 12mo). MRI of 8 patients showed osteochondral graft integration with a mean magnetic resonance observation of cartilage repair tissue 2.0 score of 86.9 (SD: 7, range: 80 to 100). Six knees showed Kellgren-Lawrence grade 0 joint space on radiographs, and 3 showed grade 1. Eight patients were asymptomatic at the last follow-up, and 1 reported occasional mild pain with intense physical activity. One patient developed arthrofibrosis, requiring arthroscopic lysis of adhesions and manipulation. Osteochondral autograft transplantation is a safe and effective technique for treating symptomatic patellar full-thickness chondral lesions in adolescents. Long-term follow-up studies will determine whether the affected area maintains structural and functional integrity over time. Level IV-therapeutic study.

Influencing factors analysis of asymmetry in knee adduction moment among patients with unilateral knee osteoarthritis

BackgroundThe knee adduction moment(KAM) of both lower limbs in patients with unilateral knee osteoarthritis(KOA) exhibits asymmetry during walking, but the factors influencing this asymmetry remain unclear. This study aimed to explore the influencing factors of KAM asymmetry in patients with unilateral KOA.MethodsA total of 148 patients with unilateral medial compartment KOA were selected for this retrospective study, and general data such as gender, age, and duration of disease were collected. The hip-knee-ankle (HKA) angle, degree of pain, and knee-extension muscle strength on the affected side were assessed through radiographic outcomes, the visual analog scale(VAS), and the Biodex isokinetic system. The peak KAM of both lower limbs was analyzed using a BTS motion-capture system and force platform. The asymmetry index(ASI) of KAM was calculated, and the patients were further categorized into the KAM symmetry group(ASI value ≤ 10%) and the KAM asymmetry group(ASI value>10%).Binary logistic regression analysis was employed to analyze the factors influencing the asymmetry of KAM.Results90 patients were categorized into the KAM asymmetry group, representing 60.8% of the cohort. A significant difference in the ASI value of KAM was observed between the two groups. Correlation analysis identified nine factors, including sex, age, and BMI, that were positively correlated with the ASI value of KAM. In contrast, knee-extension muscle strength and per-capita monthly household income were negatively correlated with the ASI value of KAM. Regression analysis revealed that being female(OR = 1.752), older age(OR = 2.472), increased BMI(OR = 1.535), larger varus angle(OR = 3.965), higher VAS score(OR = 2.617), Kellgren-Lawrence(K-L) grade IV(OR = 4.474), history of knee joint trauma(OR = 5.684), and living in a rural location(OR = 1.554) increased the risk of KAM asymmetry. Conversely, increased knee-extension muscle strength(OR = 0.758) and a per-capita monthly household income of 3000 ~ 6000 yuan(OR = 0.814) decreased the risk of KAM asymmetry.ConclusionFemale gender, older age, increased BMI, larger varus angle, higher VAS score, K-L grade IV, history of knee joint trauma, and living in a rural location are identified as risk factors for KAM asymmetry. Conversely, increased knee-extension muscle strength and a per-capita monthly household income of 3000 ~ 6000 yuan serve as protective factors against this asymmetry.

Medial Joint Opening in the Operated Knee After Unilateral High Tibial Osteotomy: Risk of Osteoarthritis and Future Surgery in the Operated and Nonoperated Knee.

High tibial osteotomy (HTO) modifies the mechanics of the affected knee but can also affect the nonoperated knee. However, no research has reported on the prognosis and risk factors related to the nonoperated knee after unilateral HTO. To assess the radiological parameters associated with osteoarthritis (OA) progression and the need for surgery in the nonoperated knee after unilateral HTO, with concurrent assessment of the operated knee. Case series; Level of evidence, 4. The medical charts of 197 patients with knee OA who underwent unilateral HTO between March 2007 and December 2020 were retrospectively investigated. Radiological parameters such as the Kellgren-Lawrence grade, weightbearing line ratio, joint line convergence angle (JLCA), and joint line obliquity angle were assessed preoperatively and 1 year postoperatively. The mean follow-up length for the 197 patients was 5.9 ± 3.2 years for the operated knee and 5.5 ± 3.2 years for the nonoperated knee. A smaller postoperative JLCA in the operated knee was a significant risk factor for OA progression (P = .027) and undergoing surgery (P = .006) in the nonoperated knee. Conversely, a larger postoperative JLCA in the operated knee was a significant risk factor for OA progression (P = .014) and conversion to arthroplasty (P = .027) in the operated knee. A postoperative JLCA >1.5° (P < .001) and <3.9° (P < .001) was needed to reduce the risk of undergoing surgery in the nonoperated knee and OA progression in the operated knee, respectively. Additionally, a pre- to postoperative change in the JLCA (ΔJLCA) between -5.6° and -1.7° (P = .021 and P = .004, respectively) was needed to reduce the risk of OA progression in both knees. A large medial joint opening (a small postoperative JLCA) in the operated knee after unilateral HTO was associated with a higher risk of OA progression and surgery in the nonoperated knee. Conversely, a small medial joint opening (a large postoperative JLCA) was associated with a higher risk of OA progression and conversion to arthroplasty in the operated knee. For a balanced medial joint opening, if the postoperative JLCA was between 1.5° and 3.9° or the ΔJLCA was between -5.6° and -1.7°, a favorable prognosis in both knees could be anticipated.

Deep learning to combat knee osteoarthritis and severity assessment by using CNN-based classification

BackgroundIn today’s digital age, various diseases drastically reduce people’s quality of life. Arthritis is one amongst the most common and debilitating maladies. Osteoarthritis affects several joints, including the hands, knees, spine, and hips. This study focuses on the medical disorder underlying Knee Osteoarthritis (KOA) which severely impairs people’s quality of life. KOA is characterised by restricted mobility, stiffness, and terrible pain and can be caused by a range of factors such as ageing, obesity, and traumas. This degenerative disorder leads to progressive wear and tear of the knee joint.MethodsTo combat arthritis in the kneecap, this study employs a 12-layer Convolutional Neural Network (CNN) to reach deep learning capabilities. A collection of data from the Osteoarthritis Initiative (OAI) is used to classify KOA. Through the use of medical image processing; the study ascertains whether an individual has this ailment. A sophisticated CNN architecture created especially for binary classification and KOA severity utilising deep learning algorithms is the main component of this work.ResultsThe cross-entropy loss function is an important component of the model’s laborious design that classifies data into two groups. The remaining section uses the Kellgren-Lawrence (KL) grade to classify the disease’s severity. In the binary classification, the proposed algorithm outperforms previous methods with an accuracy rate of 92.3%, and in the multiclassification, its accuracy rate is 78.4% which is superior to the previous findings.ConclusionLooking ahead, the research broadens the scope of this work by gathering information from various sources and using these methods on a wider range of datasets and situations. The potential for major advancements in the field of osteoarthritis detection and classification is highlighted by this forward-looking approach. Furthermore, this method reduces the intervention of medical practitioners and ultimately results in accurate diagnosis.Clinical trial numberNot applicable.

Influence of Platelet Concentration on the Clinical Outcome of Platelet-Rich Plasma Injections in Knee Osteoarthritis.

Platelet-rich plasma (PRP) is one of the most frequently used orthobiologic products for the injection treatment of patients affected by knee osteoarthritis (OA). Some preliminary evidence supports the influence of platelet concentration on patients' clinical outcomes. To analyze if platelet concentration can influence the safety and clinical efficacy of PRP injections for the treatment of patients with knee OA. Cohort study; Level of evidence, 3. This study consisted of 253 patients with knee OA (142 men, 111 women; mean ± SD age, 54.8 ± 11.4 years; Kellgren-Lawrence grades 1-3) who were treated with 3 intra-articular injections of 5 mL of autologous leukocyte-rich or leukocyte-poor PRP. All patients were prospectively evaluated at baseline and at 2, 6, and 12 months. Patients were clinically assessed thorough the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales and the International Knee Documentation Committee (IKDC) Subjective score. Platelet concentration was correlated with clinical outcome. Further analysis was performed by stratifying patients into 3 groups (homogeneous for OA severity) based on platelet concentration (high, medium, and low). All complications and adverse events were reported, as well as failures. An overall statistically significant improvement in all clinical scores was documented from baseline to each follow-up evaluation. Platelet concentration positively correlated with clinical outcome. KOOS Pain improved more with higher platelet concentration at 2 months (P = .036; rho = 0.132), 6 months (P = .009; rho = 0.165), and 12 months (P = .014; rho = 0.155). The same trend was shown by the other KOOS subscales and by the IKDC Subjective score, as well as by the comparison of the groups of high-, medium-, and low-platelet PRP. The highest failure rate (15.0%) was found in the low-platelet group as compared with the medium-platelet group (3.3%) and the high-platelet group (3.3%). No differences were observed among the 3 groups in terms of adverse events. This study demonstrated that platelet concentration influences the clinical outcome of PRP injections in knee OA treatment. PRP with a higher platelet concentration provides a lower failure rate and higher clinical improvement as compared with PRP with a lower platelet concentration, with overall better results up to 12 months of follow-up in patients with knee OA.

An Evaluation of Intra-articular Pathologies Accompanying Tibial Plateau Fractures Postoperatively.

Tibial plateau fractures are one of the most complex and common intra-articular fractures encountered in trauma surgery. This study aimsto evaluate the MRI intra-articular findings of patients with tibial plateau fractures treated surgically and the functional and radiological changes after surgical treatment. A total of 91 patients admitted to our clinic between 2010 and 2019 and operated for tibial plateau fracture were identified from the hospital information system. Patients were excluded fromthe study if aged <18 years, if the radiographs and MRIs were not suitable for the measurements, or if they could not be contacted by telephone. The study was completed with 49 operated knees and 49 healthy knees of 49 patients. The patients were evaluated with respect to demographic characteristics, KneeSocietyKneeScore (KSKS), KneeSocietyFunction Score (KSFS), KneeInjuryandOsteoarthritisOutcomeScore (KOOS) functional and clinical scores, Rasmussen, Kellgren-Lawrence, and Whole-OrganMagneticResonanceImagingScore (WORMS) radiological scoring, and meniscus and ligament pathologies examined on the follow-up MR images. The patients comprised 39 males and 10 females with a mean age of 45.9±11.89 years, and a mean follow-up of 58.2±30.7 months. The fractures were seen to be 49% (n=24)in the lateral plateau, 6.1% (n=4) in the medial plateau, and 42.9% (n=21) were bicondylar fractures involving both plateaux. The KSKS knee score was satisfactory in 85.7% of the patients, the KSFS functional score in 89.7%, and the Rassmussen radiological score in 93.8%. In the KOOS subjective questionnaire, the mean points obtained were 430.7, and the mean total WORMS points were 34.2. According to the Kellgren-Lawrence grades, severe osteoarthritis (grade 3-4) developed in 18.3% (n=9) of the patients. Meniscus injuries that are overlooked at the time of the first injury or which may develop in the subsequent process were not found to seriously affect the functional outcomes of tibial plateau fractures. It can be considered that even if a ligament injury is seen to be accompanying the fracture at the time of the first trauma, the effect is not great in terms of prognosis, and the treatment can remain conservative, especially for collateral ligament injuries.

Leukocytes Do Not Influence the Safety and Efficacy of Platelet-Rich Plasma Injections for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Controlled Trial.

Platelet-rich plasma (PRP) is increasingly used for the injection treatment of knee osteoarthritis (OA). However, the role of leukocytes contained in PRP is controversial, with some preclinical studies suggesting detrimental effects and others emphasizing their contribution in secreting bioactive molecules. To compare the safety and effectiveness of leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) for the treatment of knee OA. That leukocytes could influence results both in terms of adverse events and clinical outcomes. Randomized controlled trial; Level of evidence, 1. This double-blind randomized controlled trial included 132 patients with Kellgren-Lawrence grade 1-3 knee OA who were randomized to a 3-injection cycle of either LR-PRP or LP-PRP. Patients were prospectively assessed at baseline and at 2, 6, and 12 months with subjective evaluations comprising the International Knee Documentation Committee (IKDC) subjective score, the KOOS (Knee injury and Osteoarthritis Outcome Score), the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), the visual analog scale for pain, the EuroQol-visual analog scale, the EuroQol-5 dimensions, and the Tegner activity scale. Objective evaluations consisted of the IKDC objective score, active/passive range of motion, and circumference of the index and contralateral knees. Patient judgment of the treatment was recorded as well as adverse reactions and failures. An overall improvement in subjective and objective outcomes was documented, with no differences between the 2 groups, except for the improvement in the IKDC subjective score at 2 months, which was greater for the LR-PRP group compared with the LP-PRP group (14.8 ± 14.8 vs 8.6 ± 13.3, respectively; P = .046), as well as for active (P = .021) and passive (P = .040) ROM of the index knee at 6 months, showing statistically significant higher values in the LP-PRP group; and for quadriceps circumference of the index (P = .042) and contralateral (P = .045) knees at 12 months, which were significantly greater in the LR-PRP group. The IKDC subjective score improved from 42.5 ± 17.6 at baseline to 55.6 ± 21.4 at 12 months for the LR-PRP group (P < .0005) and from 45.7 ± 16.4 to 55.3 ± 20.4 for the LP-PRP group (P = .001). No differences in terms of patient treatment judgment were observed at all follow-up time points. No severe adverse events related to the treatment were reported, but some mild adverse events related to the treatment were observed: 16 in the LR-PRP group and 17 in the LP-PRP group. Treatment failed in 5 patients in the LR-PRP group and 2 in the LP-PRP group. This double-blind randomized controlled trial demonstrated that leukocytes did not affect the safety and efficacy of intra-articular PRP injections for the treatment of patients with knee OA. Both LR-PRP and LP-PRP demonstrated comparable clinical outcomes at all follow-up time points, without showing differences in subjective and objective outcomes or in adverse events and treatment failures. NCT04187183 (ClinicalTrials.gov).

Efficacy and safety of a diffusion-based extended-release fluticasone propionate intra-articular injection (EP-104IAR) in knee osteoarthritis (SPRINGBOARD): a 24-week, multicentre, randomised, double-blind, vehicle-controlled, phase 2 trial.

Corticosteroids are among the few effective treatments for knee osteoarthritis, but short duration of action limits their utility. EP-104IAR, a long-acting formulation of fluticasone propionate for intra-articular injection, optimises the action of fluticasone propionate through novel diffusion-based extended-release technology. The SPRINGBOARD trial assessed the efficacy, safety, and pharmacokinetics of EP-104IAR in people with knee osteoarthritis. SPRINGBOARD was a randomised, vehicle-controlled, double-blind, phase 2 trial done at 12 research sites in Denmark, Poland, and Czech Republic. We recruited adults aged 40 years or older with primary knee osteoarthritis (Kellgren-Lawrence grade 2-3) who reported Western Ontario and McMaster Universities Osteoarthritis Arthritis Index (WOMAC) pain scores of at least 4 and no more than 9 out of 10. Participants were randomly assigned (1:1) to receive one intra-articular dose of 25 mg EP-104IAR or vehicle control. Randomisation was done via interactive web-based access to a central predefined computer-generated list with block size of six (allocated by clinical site). Participants and assessors were masked to treatment allocation. Participants were followed up for 24 weeks. The primary outcome was the difference between groups in change in WOMAC pain score from baseline to week 12, analysed in all participants who were randomly assigned and received treatment. Safety, including laboratory analyses, and pharmacokinetics from quantification of fluticasone propionate in peripheral blood were assessed in all participants who received a dose of randomly assigned treatment. A person with lived experience of knee osteoarthritis was involved in study interpretation and writing of the report. This trial is registered with ClinicalTrials.gov, NCT04120402, and the EU Clinical Trials Register, EudraCT 2021-000859-39, and is complete. Between Sept 10, 2021, and Nov 16, 2022, 1294 people were screened for eligibility, and 319 were randomly assigned to EP-104IAR (n=164) or vehicle control (n=155). One participant in the EP-104IAR group was excluded from all analyses because treatment was not administered due to an adverse event. 318 participants (135 [42%] male and 183 [58%] female, 315 [99%] White) received randomly assigned treatment and were included in the primary analysis and safety analysis (EP-104IAR, n=163; vehicle control, n=155). At week 12, least squares mean change in WOMAC pain score from baseline was -2·89 (95% CI -3·22 to -2·56) in the EP-104IAR group and -2·23 (-2·56 to -1·89) in the vehicle control group, with a between-group difference of -0·66 (-1·11 to -0·21; p=0·0044); a significant between-group difference persisted to week 14. 106 (65%) of 163 participants in the EP-104IAR group had one or more treatment-emergent adverse event compared with 89 (57%) of 155 participants in the vehicle control group. Effects on serum glucose and cortisol concentrations were minimal and transient. There were no treatment-emergent deaths or treatment-related serious adverse events. Plasma concentrations of fluticasone propionate showed a blunted initial peak with terminal half-life of approximately 18-20 weeks. These phase 2 results suggest that EP-104IAR has the potential to offer clinically meaningful pain relief in knee osteoarthritis for an extended period of up to 14 weeks, longer than published data for currently marketed corticosteroids. There were minimal effects on glucose and cortisol, and stable fluticasone propionate concentrations in plasma. The safety and efficacy of EP-104IAR will be further evaluated in phase 3 trials, including the possibility of bilateral and repeat dosing with EP-104IAR. Eupraxia Pharmaceuticals. For the Danish translation of the abstract see Supplementary Materials section.

Influence of Knee Osteoarthritis Severity, Knee Pain, and Depression on Physical Function: A Cross-Sectional Study.

Decreased physical function with increasing life expectancy is a public health concern worldwide. Knee osteoarthritis (KOA) is considered one of the primary illnesses causing decreased physical function. Depression affects decreased physical function and is closely related to knee pain in KOA. However, the effect of these interacting factors on physical function is not clear. We conducted a cross-sectional analysis of the baseline data of 1106 subjects of the 2009 Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS). We determined the association between their Timed Up and Go test (TUG) scores and radiographic KOA, knee pain, and depression in a multivariate analysis. Severe knee pain was significantly associated with decreased physical function (the odds ratio [OR] was 2.13, 95% confidence interval [CI]: 1.32-4.89), as was depression (OR 2.64, 95% CI 1.61-4.33). Only Kellgren-Lawrence (KL) grade 4 was significantly associated with decreased physical function in the radiographic KOA severity (OR 6.58, 95% CI 1.75-24.68). Severe knee pain and depression were significantly associated with decreased physical function, but not radiographic KOA severity except for KL grade 4. The limitations of using radiographic KOA severity alone as the indicator of assessment for physical function were suggested. When assessing decreased physical function, the clinical focus tends to be on radiographic KOA severity, but it is important to consider the patient's knee pain and psychological factors.

Development of the machine learning model that is highly validated and easily applicable to predict radiographic knee osteoarthritis progression.

Many models using the aid of artificial intelligence have been recently proposed to predict the progression of knee osteoarthritis. However, previous models have not been properly validated with an external data set or have reported poor predictive performances. Therefore, the purpose of this study was to design a machine learning model for knee osteoarthritis progression, focusing on high validation quality and clinical applicability. A retrospective analysis was conducted on prospectively collected data, using the Osteoarthritis Initiative data set (5966 knees) for model development and the Multicenter Osteoarthritis Study data set (3392 knees) for validation. The analysis aimed to predict Kellgren-Lawrence grade (KLG) progression over 4-5 years in knees with initial KLG of 0, 1, or 2. Possible predictors included demographics, comorbidities, history of meniscectomy, gait speed, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and radiological findings. The Random Forest algorithm was employed for the predictive model development. Baseline KLG, contralateral knee osteoarthritis, lateral joint space narrowing (JSN) grade, BMI, medial JSN grade, and total WOMAC score were six features selected for the model in descending order of importance. Odds ratios of baseline KLG, contralateral knee osteoarthritis, and lateral JSN grade were 1.76, 2.59, and 4.74, respectively (all p < 0.001). The area-under-the-curve of the ROC curve in the validation set was 0.76 with an accuracy of 0.68 and an F1-score of 0.56. The progression of knee osteoarthritis in 4 ~ 5 years could be well-predicted using easily available variables. This simple and validated model may aid surgeons in knee osteoarthritis patient management.

Complications and Radiographic Outcomes of Tibial Tubercle Osteotomy at Minimum 5-Year Follow-up.

Tibial tubercle osteotomy (TTO) is a commonly utilized surgery in the treatment of patellofemoral instability and chondrosis. A number of case series studies have reported on the mid- and long-term outcomes with varying complication rates. To report the incidence of major complications after TTO and the rate of progression of knee osteoarthritis at midterm follow-up. Case series; Level of evidence, 4. All patients who underwent primary TTO between January 1, 2010 and December 31, 2015, and who had ≥5 years of clinical follow-up data were included. Patient demographics and clinical and radiographic outcomes were recorded. Risk factors for complications were identified using multivariate logistic regression analysis. A total of 72 patients were included. The mean follow-up period was 104.8 months (range, 67-138 months). The overall complication rate was 38.9% (28/72 patients), and the incidence of major complications was 6.9%. Univariate logistic regression analysis revealed that patients with a history of smoking were more likely to experience a complication (odds ratio = 4.33 [95% CI, 1.29-14.53]; P = .02). Multivariate analysis with TTO as the main predictor indicated that complication rates were not affected by TTO procedure (TTO vs TTO+other), number of screws, or distalization. There was also no difference between anteromedialization and medialization TTO techniques. The rate of patients with Kellgren-Lawrence grade 3 to 4 increased from 12.0% preoperatively to 23.9% at the final follow-up. New osteophyte formation was detected in 5.8% of patients on anteroposterior radiographs and in 9.1% of patients on lateral radiographs. In the current study, TTO was found to have a major complication rate of 6.9% at midterm follow-up. Smoking was a risk factor for major complications. Only 11.9% of patients had progression in tibiofemoral osteoarthritis at midterm follow-up.

Deep Learning for Automatic Knee Osteoarthritis Severity Grading and Classification.

Knee osteoarthritis (OA) is a prevalent condition that significantly impacts the quality of life, often leading to the need for knee replacement surgery. Accurate and timely identification of knee degeneration is crucial for effective treatment and management. Traditional methods of diagnosing OA rely heavily on radiological assessments, which can be time-consuming and subjective. This study aims to address these challenges by developing a deep learning-based method to predict the likelihood of knee replacement and the Kellgren-Lawrence (KL) grade of knee OA from X-ray images. We employed the Osteoarthritis Initiative (OAI) dataset and utilized a transfer learning approach with the Inception V3 architecture to enhance the accuracy of OA detection. Our approach involved training 14 different models-Xception, VGG16, VGG19, ResNet50, ResNet101, ResNet152, ResNet50V2, ResNet101V2, ResNet152V2, Inception V3, Inception, ResNetV2, DenseNet121, DenseNet169, DenseNet201-and comparing their performance. The study incorporated pixel ratio computation and picture pre-processing, alongside a decision tree model for prediction. Our experiments revealed that the Inception V3 model achieved the highest training accuracy of 91% and testing accuracy of 67%, with notable performance in both training and validation phases. This model effectively identified the presence and severity of OA, correlating with the Kellgren-Lawrence scale and facilitating the assessment of knee replacement needs. By integrating advanced deep learning techniques with radiological diagnostics, our methodology supports radiologists in making more accurate and prompt decisions regarding knee degeneration. The Inception V3 model stands out as the optimal choice for knee X-ray analysis, contributing to more efficient and timely healthcare delivery for patients with knee osteoarthritis.

Efficacy of a single dose of cryopreserved human umbilical cord mesenchymal stromal cells for the treatment of knee osteoarthritis: a randomized, controlled, double-blind pilot study.

Knee osteoarthritis (OA) is the most prevalent degenerative musculoskeletal disorder, which is particularly common in older population. While conventional treatments have limited effectiveness, the development of more effective therapeutic strategies is necessary to address this primary source of pain and disability. Umbilical cord mesenchymal stromal cells (UC-MSCs) offer a promising therapeutic approach for treating knee OA.This randomized, prospective, double-blind and controlled pilot study was carried out to evaluate and compare the safety and therapeutic efficacy of a single intra-articular injection of a standardized product CellistemTMOA (5 × 106 ± 5 × 105 UC-MSCs), vs. triamcinolone (a synthetic corticosteroid) (10 mg/mL) in thirty patients with symptomatic knee OA (Kellgren-Lawrence grade II or III).The outcomes included changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores based on a Likert scale, numerical rating score (NRS) for pain, Magnetic Resonance Imaging (MRI), and quality of life (SF-36 questionnaire), from baseline and throughout 12-months of follow-up.Patients treated with CellistemTMOA showed significant improvement in WOMAC score (including the three subscale scores (pain, stiffness and function), NRS in pain, and SF-36 profile from baseline to 12 months (p < 0.05) compared to the triamcinolone group, and no severe adverse events were reported.There were no significant differences in MRI WORMS scores between the two groups. However, patients who received the cellular treatment experienced a significant improvement in their SF-36 profile (p < 0.05).This pilot study revealed that a single dose of CellistemTMOA is safe and superior to the active comparator in knee OA at 1-year of follow-up, making it a compelling therapeutic alternative to treat symptomatic OA patients.

Factors affecting the therapeutic effects of multiple intra-articular injections of platelet-rich-plasma for knee osteoarthritis

BackgroundPlatelet-rich-plasma (PRP) is rapidly spreading as a conservative treatment option for knee osteoarthritis (KOA), however, its therapeutic efficacy is controversial. This study aimed to investigate the factors affecting the therapeutic effect of intra-articular PRP therapy for KOA in patients who received multiple PRP injections (PRP-I). MethodsThis is a historical cohort study included 1057 knees of 701 patients who received PRP-I during KOA treatment from 2018 to 2020. The difference in visual analog scale (VAS) scores before and after PRP-I was defined as the amount of change in VAS (ΔVAS). A linear mixed-effects model was employed with ΔVAS as a random effect and age, sex, BMI, KL classification, pre-treatment VAS, treatment duration, and the number of PRP injections as fixed effects. Evaluations using the Kellgren-Lawrence (KL) classification were added. ResultsAge, KL grade, and VAS score before treatment and after three, four, and five PRP-I were significantly associated with ΔVAS score. According to KL grade, age was significantly associated with ΔVAS score in the KL grade 4 group. VAS score before treatment was significantly associated with ΔVAS score, regardless of KL grade. Three-time PRP-I were significantly associated with ΔVAS in the KL-grade 1 and 2 groups. For KL grade 4, two or more PRP-I were significantly associated with the high efficacy. ConclusionsAge, pain before treatment, KL grade and number of injections were associated with pain reduction after intra-articular PRP-I for KOA treatment. Pain reduction can be expected after PRP-I when patients are younger or experience severe pain before treatment. Three-time PRP-I are recommended to reduce pain in early-stage KOA and more than three times in advanced-stage KOA. Trial registrationRetrospectively registration.

Autograft and Allograft ACLR in Patients Greater Than 40 Years Old Have Similar Short-Term Patient-Reported Outcomes with Higher Rates of ACL Graft Failure in Allograft Patients

PurposeThe purpose of this study was to evaluate short-term patient-reported outcomes (PROs) in patients aged 40 and older after primary ACLR between patients that received allograft or autograft. Secondary aims included assessing the effect of pre-existing osteoarthritis on short-term PROs. MethodsA retrospective review of an ambulatory surgery center’s electronic medical record was conducted for patients who underwent primary ACLR between 2009 and 2022. Patients aged younger than 40, those who underwent index revision procedures and/or concomitant ligament repair/reconstructions, and those with incomplete baseline or short-term (1- or 2-year) KOOS scores were excluded. Allograft and autograft patients were matched according to sex and body mass index (BMI) in a 2:1 fashion. PROs used included KOOS and Single Assessment Numeric Evaluation (SANE) at baseline and short-term follow up (minimum of 1 year). Minimum clinically important difference was calculated in a distribution-based fashion. Osteoarthritis severity was determined based on Kellgren-Lawrence grading of perioperative knee x-rays. Preexisting osteoarthritis was defined as KL grade 1 or more. ResultsA total of 331 patients were included after matching (215 allograft and 116 autograft patients). The average age was 47.7 ± 6.0 (range: 40-66). Age differed significantly between the two groups, with the allograft cohort having an average age of 48.6 ± 6.0 years and the autograft cohort having an average age of 46.1 ± 5.7 years (p < 0.001). Short-term change in KOOS and SANE scores did not differ by graft type (p = 0.154, p = 0.556, respectively). Sixty-seven percent of all patients met MCID for KOOS and 82% of patients with complete baseline and short-term SANE scores met MCID for SANE. There was a statistically significant difference in rupture rates between the allograft and autograft cohorts (n = 9 allograft vs n = 0 autograft; p = 0.030). There was no difference in re-operation rates between the autograft and allograft cohorts (p = 0.453). Perioperative Kellgren-Lawrence grading did not affect outcomes for either graft type (allograft: p = 0.905 vs. autograft: p = 0.522). ConclusionMiddle-aged patients undergoing ACLR with allograft or autograft demonstrate similar short-term patient reported outcomes. Pre-existing osteoarthritis similarly did not significantly affect short-term outcomes. However, rerupture rates were significantly higher in the allograft cohort than the autograft cohort. Level of EvidenceLevel III - Therapeutic

Application of remote sensing navigation system in total knee arthroplasty

To explore clinical accuracy of remote sensing navigation alignment (RSNA) system in total knee arthroplasty (TKA) and its influence on postoperative clinical efficacy. From May 2021 to May 2022, 60 knee osteoarthritis (KOA) patients with Kellgren-Lawrence (K-L) grade Ⅲ to Ⅳ treated by unilateral primary TKA were selected and divided into RSNA group and traditional operation group according to treatment methods, and 30 patients in each group. There were 6 males and 24 females in RSNA group, aged from 55 to 86 years old with an average of (68.06±8.23) years old;body mass index (BMI) ranged from 22.15 to 34.58 kg·m-2 with an average of (28.20±3.01) kg·m-2;the courses of disease ranged from 2 to 60 months with an average of (18.80±14.80) months;13 patients with grade Ⅲ and 17 patients with grade Ⅳ according to K-L grading. In traditional operation group, there were 8 males and 22 females, aged from 57 to 85 years old with an average of (67.26±6.32) years old;BMI ranged from 23.94 to 34.55 kg·m-2 with an average of (27.49±2.32) kg·m-2;the courses of disease ranged from 3 to 60 months with an average of (21.30±16.44) months;14 patients with grade Ⅲ and 16 patients with grade Ⅳ according to K-L grading. Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and Knee Society score(KSS) were used to evaluate functional recovery of patients. Hip-knee-ankle angle (HKAA), distal femoral valgus angle (FVA) and distal fermoral flexion angle (DFFA) were measured before operation. HKAA and HKAA deviation angle were measured at 1 week after operation, and defective rate of lower limb force line, femur prosthesis valgus angle (FPVA) and femoral prosthesis flexion angle (FPFA), respectively, were calculated. There were no serious complications such as vascular and nerve injury during operation, and wound healed at stage Ⅰ. Both groups were followed up for 6 months. There were no significant difference in WOMAC index, KSS, HKAA, FVA and DFFA between two groups before operation (P>0.05). The force line defect rate, HKAA, HKAA deviation angle, FPVA deviation angle and FPFA of RSNA group were 6.7%, (178.74±1.56) °, (1.25±1.56) °, (1.84±0.16) ° and (4.85±2.46) °, respectively;while in traditional operation group were 20%, (176.73±3.46) °, (3.27±3.46) °, (2.44±0.26) °, (6.60±1.86) °;the difference between two groups were statistically significant (P<0.05). There were no significant difference in WOMAC index and KSS between two groups at 3 and 6 months after operation (P>0.05). RSNA system could reduce defective rate of lower limb force line, FPVA deviation angle and FPFA after TKA, which is more accurate and easy to operate than traditional intramedullary localization surgery while ensuring postoperative efficacy.

Generative AI in orthopedics: an explainable deep few-shot image augmentation pipeline for plain knee radiographs and Kellgren-Lawrence grading.

Recently, deep learning medical image analysis in orthopedics has become highly active. However, progress has been restricted by the absence of large-scale and standardized ground-truth images. To the best of our knowledge, this study is the first to propose an innovative solution, namely a deep few-shot image augmentation pipeline, that addresses this challenge by synthetically generating knee radiographs for training downstream tasks, with a specific focus on knee osteoarthritis Kellgren-Lawrence (KL) grading. This study leverages a deep few-shot image augmentation pipeline to generate synthetic knee radiographs. Despite the limited availability of training samples, we demonstrate the capability of our proposed computational strategy to produce high-fidelity plain knee radiographs and use them to successfully train a KL grade classifier. Our experimental results showcase the effectiveness of the proposed computational pipeline. The generated synthetic radiographs exhibit remarkable fidelity, evidenced by the achieved average Frechet Inception Distance (FID) score of 26.33 for KL grading and 22.538 for bilateral knee radiographs. For KL grading classification, the classifier achieved a test Cohen's Kappa and accuracy of 0.451 and 0.727, respectively. Our computational strategy also resulted in a publicly and freely available imaging dataset of 86000 synthetic knee radiographs. Our approach demonstrates the capability to produce top-notch synthetic knee radiographs and use them for KL grading classification, even when working with a constrained training dataset. The results obtained emphasize the effectiveness of the pipeline in augmenting datasets for knee osteoarthritis research, opening doors for broader applications in orthopedics, medical image analysis, and AI-powered diagnosis.