human knee joint
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Background: It is well understood that distal femoral and proximal tibia scale is lower in case of the Asian than that of their western counterparts. Because of the Asian population's comparatively smaller structure and stature, many surgeons claim that imported implants may not be well fitted for Asian origin patients, mainly based on Western morphometry. It is very likely that an overweight section will be used in many Asian centres in most operations, resulting in low results of the procedure of the implant. For joint substitution of distal femur, careful positioning of fitted implants as well as balancing of underlying soft tissues is important. It is also important to use incredibly complex surgical procedures. To retain its usual functional motion spectrum, use of a suitable femoral part dimension is necessary. Furthermore, owing to a discrepancy between the size of the prosthesis and the bone, there could be a host of serious issues. Objectives: To calculate the anthropometric distal femur parameter and determine the distal femur variations on the right and left side of the morph metric measurement and to evaluate dimension of current TKA as related to Indian population. Methodology: This study included visiting the out patients Department of Orthopedics, at AVBRH in the age group 30-50 year during the period of June-2020 to April-2023 with sample size of 50 patients. Detailed history and clinical review will be taken, including age, sex, socio-economic background, type of employment. In all patients involved in the study in Orthopedic OPD, thorough radiological assessment of all the knee joints will be performed. The radiological test and various anthropometrics will include knee joint Simple X-ray and CT-Scan. Expected Results: We expect that from our results, anthropometric measurements of Indian population may differ from other literatures.

Abstract Background The fabella is a sesamoid bone in the posterolateral capsule of the human knee joint. In quadrupedal mammals, the fabella is believed to have a role similar to the patella in redirecting extension forces of the knee joint from one point to another. In bipeds, the fabella is not touching the back of the bent knee, and therefore the role in redirecting forces declines. Posterolateral knee pain can be associated with the irritation between the fabella and lateral femoral condyle, a phenomenon also known as fabella syndrome. In cases that are unresponsive to conservative management, surgical fabellectomy can be a successful treatment option. Among the surgical approaches, open resection is most commonly seen. There are also literature reporting arthroscopic-assisted open resection, but seldom mentioned the all-arthroscopic fabellectomy. Case presentation We present 3 patients with a long history (> 12 month) of posterolateral knee pain under suspicion of different pain origins. The diagnosis of fabella impingement was eventually made by ruling out of other causes. All the patients underwent all-arthroscopic fabellectomy for diagnosis and treatment. Investigations of the resected fabella suggested chronic impingement with apparent osteophyte formation and cartilage wearing of the articular side. All patients have been continually followed up at our outpatient department and reported to be pain free after the procedure. Conclusions In the patients presenting posterolateral pain, fabella syndrome cannot be ignored due to its relative higher presence in Asian population. In our experience, the all-arthroscopic fabellectomy offers a smaller wound size, less post-operative pain, fewer days of hospitalization and quicker time to rehabilitation for the patients with chronic posterolateral knee pain caused by fabella syndrome.

Stress MRI brings together mechanical loading and MRI in the functional assessment of cartilage and meniscus, yet lacks basic scientific validation. This study assessed the response-to-loading patterns of cartilage and meniscus incurred by standardized compartmental varus and valgus loading of the human knee joint. Eight human cadaveric knee joints underwent imaging by morphologic (i.e., proton density-weighted fat-saturated and 3D water-selective) and quantitative (i.e., T1ρ and T2 mapping) sequences, both unloaded and loaded to 73.5 N, 147.1 N, and 220.6 N of compartmental pressurization. After manual segmentation of cartilage and meniscus, morphometric measures and T2 and T1ρ relaxation times were quantified. CT-based analysis of joint alignment and histologic and biomechanical tissue measures served as references. Under loading, we observed significant decreases in cartilage thickness (p < 0.001 (repeated measures ANOVA)) and T1ρ relaxation times (p = 0.001; medial meniscus, lateral tibia; (Friedman test)), significant increases in T2 relaxation times (p ≤ 0.004; medial femur, lateral tibia; (Friedman test)), and adaptive joint motion. In conclusion, varus and valgus stress MRI induces meaningful changes in cartilage and meniscus secondary to compartmental loading that may be assessed by cartilage morphometric measures as well as T2 and T1ρ mapping as imaging surrogates of tissue functionality.

Abstract Earlier identification of knee joint pathology helps the therapist to provide the appropriate clinical procedures to control the deteriorating process of arthritis. Beyond usual medical investigations, computational techniques have been used for the diagnosis of knee joint disorder. Among different methodologies, Vibroarthrographic technique is employed to identify knee joint disorder. Machine Learning contains number of classification methods for the given data. A novel technique called Greedy sequential backward feature selection based Radial kernelized least square support vector classification (GSBFS-RKLSSVC) is introduced for accurate detection of knee joint pathology with minimum time. The proposed GSBFS-RKLSSVC technique consists of three processes namely feature selection, feature evaluation and classification. Initially number of VAG signal images are taken from the dataset for detection of knee joint disorder. The relevant feature is selected through the Greedy mutual informative regressed sequential backward selection algorithm to reduce an initial dimensional feature space into a low dimensional feature subspace. Following this the dichotomous logit regression is applied to select the best features and discard others. Therefore, the feature selection process of the proposed GSBFS-RKLSSVC minimizes the time consumption of the knee joint pathology detection. Once the signal features are extracted, RKLSSVC is applied to detect the normal and abnormal VAG signal. Decision boundary is utilized by the classifier to categorize the samples based on the similarity between the training features and testing features. As a result, the accurate classification is obtained with a minimum error rate. The observed result indicates that GSBFS-RKLSSVC achieves higher accuracy, sensitivity, specificity and reduces time than the conventional methods.

While providing the reference imaging modality for joint pathologies, MRI is focused on morphology and static configurations, thereby not fully exploiting the modality’s diagnostic capabilities. This study aimed to assess the diagnostic value of stress MRI combining imaging and loading in differentiating partial versus complete anterior cruciate ligament (ACL)-injury. Ten human cadaveric knee joint specimens were subjected to serial imaging using a 3.0T MRI scanner and a custom-made pressure-controlled loading device. Emulating the anterior-drawer test, joints were imaged before and after arthroscopic partial and complete ACL transection in the unloaded and loaded configurations using morphologic sequences. Following manual segmentations and registration of anatomic landmarks, two 3D vectors were computed between anatomic landmarks and registered coordinates. Loading-induced changes were quantified as vector lengths, angles, and projections on the x-, y-, and z-axis, related to the intact unloaded configuration, and referenced to manual measurements. Vector lengths and projections significantly increased with loading and increasing ACL injury and indicated multidimensional changes. Manual measurements confirmed gradually increasing anterior tibial translation. Beyond imaging of ligament structure and functionality, stress MRI techniques can quantify joint stability to differentiate partial and complete ACL injury and, possibly, compare surgical procedures and monitor treatment outcomes.

Background:In Osteoarthritis (OA), defects in macroautophagy (autophagy) are evident and precede joint damage. Indeed, pharmacological activation of autophagy protects against joint damage.Objectives:Therefore, identifying hallmarks associated with specific autophagy subtypes could shed light to fundamental mechanisms of joint disease.Methods:A comparative analysis of 35 autophagy genes was performed from blood from the Prospective OA Cohort of A Coruña (PROCOAC). Non-OA subjects (Age:61,44±1,16 years; BMI:25,25±0,52; Females, n=18) and Knee OA subjects (Age:65,50±1,05 years; BMI:29,55±0,67; Females, n=18, OA grade III-IV) were profiled using an autophagy gene expression array by SYBR green qPCR. Confirmatory studies were performed in blood from Non-OA subjects (Age:60,13±1,12 years; BMI:24,85±0,59; Females; n=30) and Knee-OA subjects (Age:68,4±1,11 years; BMI:29,65±0,55; Females; n=30, OA grade III-IV) by Taqman qPCR. The candidate gene was evaluated in human knee joint tissues (cartilage, meniscus, ligaments, synovium) with different KL grades (Age: KL0=28,3±4,50; KL2=77±6,08; KL4=62,3±3,05, n=3) and in both spontaneous aging (2, 6, 12, 18, and 30 months old, n=3) and surgically-induced OA (10 weeks after surgery, n=4) in mice by IHC. The functional consequences were studied in T/C28a2 and primary human OA chondrocytes. Autophagy, FOXO, Chaperone-mediated autophagy (CMA), inflammation, and cellular senescence were analyzing by gene and protein expression. Moreover, oxidative stress and cell death were evaluated by FACS. The contribution of CMA to chondrocyte homeostasis was evaluated by studying the capacity of CMA to restore proteostasis upon autophagy deficiency by siATG5.Results:15 autophagy-related genes were significantly downregulated in blood from knee OA patients compared to non-OA patients. No significant upregulation was found for any studied gene, although a trend towards upregulation was found in genes involved in the mTOR pathway. Four key autophagy-related genes, including ATG16L2, ATG12, ATG4B and MAP1LC3B were found downregulated in knee OA patients. Interestingly, HSP90AA1 and HSPA8, CMA markers involved in stress response and protein folding, were downregulated. Confirmatory studies showed a significant downregulation of MAP1LC3B and HSP90AA1 in blood from knee OA patients. Remarkably, HSP90A was found reduced in femoral cartilage (medial and lateral), meniscus and ACL. Moreover, this reduction was higher in medial cartilage compared to lateral cartilage and meniscus, while in synovial membrane, HSP90A expression was found increased. This expression signature was dependent on OA grade severity. In addition, we observed a decrease of HSP90A with aging and OA in mice. The functional consequences of HSP90AA1 gene silencing are related to an increase in NFκB, MMP13, and p16 expression. Interestingly, LAMP2A, a key CMA mediator, HSPA8, MAP1LC3B and FoxO1 expression were upregulated in chondrocytes with HSP90AA1 deficiency, which might indicate an early response to maintain homeostasis. On the other hand, LAMP2A protein is decreased upon HSP90AA1 deficiency, while LC3II and p62 were increased, indicating a failure in the autophagy flux that leads to impaired lysosomal degradation.Moreover, p21, p16 and prbS6 were increased upon HSP90AA1 deficiency, besides increasing mitochondrial ROS production and apoptosis. ATG5 silencing blocks autophagy by reducing LC3II and increasing prbs6, p62, p16 and p21. Interestingly, LAMP2A and HSP90A were found increased, indicating a possible compensative activation of CMA in response to autophagy defects. These results support that HSP90A has an important role in chondrocyte homeostasis by participating in the cross-talk between CMA and autophagy.Conclusion:Taking together, we identified HSP90A, a CMA regulator, as critical in chondrocyte homeostasis. These disease mechanisms are relevant in OA and constitute hallmarks potentially useful to prevent OA progression.References:[1]Caramés B, et al. Arthritis Rheum. 2010, 2015;[2]Caramés B, et al. Ann Rheum Dis. 2012.Disclosure of Interests:None declared

Background:While osteoarthritis (OA) is the most common joint disease worldwide, rheumatoid arthritis (RA) represents the most common type of autoimmune arthritis. In both diseases, fibroblast-like synoviocytes (FLS), which maintain the structural and dynamic integrity of the joint, have been identified as key drivers of cartilage degradation. FLS can be divided into two major populations. The destructive phenotype which is restricted to the THY1- FLS of the synovial lining promotes bone erosion, while THY1+ FLS of the sublining layer drives synovitis. The FLS phenotype is shaped by glucose metabolism, which promotes disease progression in patients with synovitis. However, profound knowledge about the contribution of FLS to pathogenic mechanisms in cartilage degradation is limited.Objectives:Here, we present the phenotypic features of FLS obtained from patients with OA (OA-FLS) compared to bone marrow-derived mesenchymal stromal cells (MSC) on transcriptomic, proteomic and metabolic levels with the aims (i) to identify novel targets for the development of disease-modifying osteoarthritis drugs and (ii) to distinguish both cell types.Methods:To this end, we comprehensively compared human bone marrow-derived MSC with OA-FLS isolated from human knee joint sections. MSC and OA-FLS were characterized in detail according to their multipotency, surface marker pattern, cell viability, proliferation rate, morphology and expression of fibroblast- and metabolic-related markers using flow cytometry, immunofluorescence and SeahorseTM. More in-depth, selected gene and protein expression patterns were analyzed using qPCR and mass spectrometry.Results:We observed a similar phenotype of OA-FLS and MSC with regard to the minimal criteria that define a MSC phenotype. In-depth comparison of OA-FLS and MSC on proteome level revealed 598 differentially expressed proteins. We observed no differences in the expression of classical fibroblast markers such as vimentin, tenascin C and decorin as confirmed on RNA level. Remarkably, fibronectin, which is mainly produced by fibroblasts, is significantly lower expressed at both protein and RNA levels in OA-FLS together with collagen type 1 and CD106. Conversely, CD9, CD54 and fibroblast-specific protein-1 were expressed significantly higher in FLS at both levels, while hyaluronan synthase 1-3 remained unchanged. Of note, in terms of mitochondrial function, human OA-FLS show a significantly lower basal respiration and ATP production than MSC, but a comparable spare respiratory capacity and cellular mitochondrial dehydrogenase activity (NADH amount) per cell. Additionally, we identified the pyruvate dehydrogenase kinase (PDK) 3 to be highly expressed in OA-FLS, while the expression of mitochondrial ATP synthase subunits, electron transport chain complexes and glycolytic enzymes was comparable with MSC. Finally, inhibition of PDK by using DCA resulted in a significant increase in oxygen consumption rate and ATP production in OA-FLS. Thus, our data newly suggest, that PDKs may play a crucial role in the pathogenesis of OA and possibly RA.Conclusion:Our data provide evidence that, although the classical fibroblast markers do not discriminate between MSC and FLS, the latter demonstrate a significantly higher expression of PDKs, known to inhibit the pyruvate entry into the TCA cycle which finally limits the mitochondrial ATP production. Therefore, shifting the metabolism of FLS from glycolysis to mitochondrial respiration via inhibition of PDKs might be a novel approach in OA for the development of disease-modifying osteoarthritis drugs in order to unleash the metabolic flow.Disclosure of Interests:None declared