Subchondral bone expansion in advanced knee osteoarthritis: Relation with radiographic severity and role in surgical decision-making.

Background: Joint space width (JSW) is a traditional imaging marker for knee osteoarthritis (OA) severity, but it lacks sensitivity in advanced cases. We propose tibial subchondral bone area (TSBA), a new CT imaging marker to explore its relationship with OA radiographic severity, and to test its performance for classifying surgical decisions between unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) compared to JSW. Methods: We collected clinical, radiograph, and CT data from 182 patients who underwent primary knee arthroplasty (73 UKA, 109 TKA). The radiographic severity was scored using Kellgren-Lawrence (KL) grading system. TSBA and JSW were extracted from 3D CT-reconstruction model. We used independent t-test to investigate the relationship between TSBA and KL grade, and binary logistic regression to identify factors associated with TKA risk. The accuracy of TSBA, JSW and established classification model in differentiating between UKA and TKA was assessed using AUC. Results: All parameters exhibited inter- and intra-class coefficients greater than 0.966. Patients with KL grade 4 had significantly larger TSBA than those with KL grade 3. TSBA (0.708 of AUC) was superior to minimal/average JSW (0.547/0.554 of AUC) associated with the risk of receiving TKA. Medial TSBA, together with gender and Knee Society Knee Score, emerged as independent classification factors in multivariate analysis. The overall AUC of composite model for surgical decision-making was 0.822. Conclusion: Tibial subchondral bone area is an independent imaging marker for radiographic severity, and is superior to JSW for surgical decision-making between UKA and TKA in advanced OA patients.

SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids.

SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages' role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.

Radiomics analysis of patellofemoral joint improves knee replacement risk prediction: Data from the Multicenter Osteoarthritis Study (MOST).

Objective: Knee replacement (KR) is the last-resort treatment for knee osteoarthritis. Although radiographic evidence of tibiofemoral joint has been widely adopted for prognostication, patellofemoral joint has gained little attention and may hold additional value for further improvements. We aimed to quantitatively analyse patellofemoral joint through radiomics analysis of lateral view radiographs for improved KR risk prediction. Design: From the Multicenter Osteoarthritis Study dataset, we retrospectively retrieved the initial-visit lateral left knee radiographs of 2943 patients aged 50 to 79. They were split into training and test cohorts at a 2:1 ratio. A comprehensive set of radiomic features were extracted within the best-performing subregion of patellofemoral joint and combined into a radiomics score (RadScore). A KR risk score, derived from Kellgren-Lawrence grade (KLG) of tibiofemoral joint and RadScore of patellofemoral joint, was developed by multivariate Cox regression and assessed using time-dependent area under receiver operating characteristic curve (AUC). Results: While patellofemoral osteoarthritis (PFOA) was insignificant during multivariate analysis, RadScore was identified as an independent risk factor (multivariate Cox p-value < 0.001) for KR. The subgroup analysis revealed that RadScore was particularly effective in predicting rapid progressor (KR occurrence before 30 months) among early- (KLG < 2) and mid-stage (KLG â€‹= â€‹2) patients. Combining two joints radiographic information, the AUC reached 0.89/0.87 for predicting 60-month KR occurrence. Conclusions: The RadScore of the patellofemoral joint on lateral radiographs emerges as an independent prognostic factor for improving KR prognosis prediction. The KR risk score could be instrumental in managing progressive knee osteoarthritis interventions.

Engineering an extracellular matrix-functionalized, load-bearing tendon substitute for effective repair of large-to-massive tendon defects.

A significant clinical challenge in large-to-massive rotator cuff tendon injuries is the need for sustaining high mechanical demands despite limited tissue regeneration, which often results in clinical repair failure with high retear rates and long-term functional deficiencies. To address this, an innovative tendon substitute named "BioTenoForce" is engineered, which uses (i) tendon extracellular matrix (tECM)'s rich biocomplexity for tendon-specific regeneration and (ii) a mechanically robust, slow degradation polyurethane elastomer to mimic native tendon's physical attributes for sustaining long-term shoulder movement. Comprehensive assessments revealed outstanding performance of BioTenoForce, characterized by robust core-shell interfacial bonding, human rotator cuff tendon-like mechanical properties, excellent suture retention, biocompatibility, and tendon differentiation of human adipose-derived stem cells. Importantly, BioTenoForce, when used as an interpositional tendon substitute, demonstrated successful integration with regenerative tissue, exhibiting remarkable efficacy in repairing large-to-massive tendon injuries in two animal models. Noteworthy outcomes include durable repair and sustained functionality with no observed breakage/rupture, accelerated recovery of rat gait performance, and >1 cm rabbit tendon regeneration with native tendon-like biomechanical attributes. The regenerated tissues showed tendon-like, wavy, aligned matrix structure, which starkly contrasts with the typical disorganized scar tissue observed after tendon injury, and was strongly correlated with tissue stiffness. Our simple yet versatile approach offers a dual-pronged, broadly applicable strategy that overcomes the limitations of poor regeneration and stringent biomechanical requirements, particularly essential for substantial defects in tendon and other load-bearing tissues.

Adaptive Fusion of Deep Learning With Statistical Anatomical Knowledge for Robust Patella Segmentation From CT Images.

Kneeosteoarthritis (KOA), as a leading joint disease, can be decided by examining the shapes of patella to spot potential abnormal variations. To assist doctors in the diagnosis of KOA, a robust automatic patella segmentation method is highly demanded in clinical practice. Deep learning methods, especially convolutional neural networks (CNNs) have been widely applied to medical image segmentation in recent years. Nevertheless, poor image quality and limited data still impose challenges to segmentation via CNNs. On the other hand, statistical shape models (SSMs) can generate shape priors which give anatomically reliable segmentation to varying instances. Thus, in this work, we propose an adaptive fusion framework, explicitly combining deep neural networks and anatomical knowledge from SSM for robust patella segmentation. Our adaptive fusion framework will accordingly adjust the weight of segmentation candidates in fusion based on their segmentation performance. We also propose a voxel-wise refinement strategy to make the segmentation of CNNs more anatomically correct. Extensive experiments and thorough assessment have been conducted on various mainstream CNN backbones for patella segmentation in low-data regimes, which demonstrate that our framework can be flexibly attached to a CNN model, significantly improving its performance when labeled training data are limited and input image data are of poor quality.

Radiomics signature of osteoarthritis: Current status and perspective.

Osteoarthritis (OA) is one of the fast-growing disability-related diseases worldwide, which has significantly affected the quality of patients' lives and brings about substantial socioeconomic burdens in medical expenditure. There is currently no cure for OA once the bone damage is established. Unfortunately, the existing radiological examination is limited to grading the disease's severity and is insufficient to precisely diagnose OA, detect early OA or predict OA progression. Therefore, there is a pressing need to develop novel approaches in medical image analysis to detect subtle changes for identifying early OA development and rapid progressors. Recently, radiomics has emerged as a unique approach to extracting high-dimensional imaging features that quantitatively characterise visible or hidden information from routine medical images. Radiomics data mining via machine learning has empowered precise diagnoses and prognoses of disease, mainly in oncology. Mounting evidence has shown its great potential in aiding the diagnosis and contributing to the study of musculoskeletal diseases. This paper will summarise the current development of radiomics at the crossroads between engineering and medicine and discuss the application and perspectives of radiomics analysis for OA diagnosis and prognosis. The translational potential of this article: Radiomics is a novel approach used in oncology, and it may also play an essential role in the diagnosis and prognosis of OA. By transforming medical images from qualitative interpretation to quantitative data, radiomics could be the solution for precise early OA detection, progression tracking, and treatment efficacy prediction. Since the application of radiomics in OA is still in the early stages and primarily focuses on fundamental studies, this review may inspire more explorations and bring more promising diagnoses, prognoses, and management results of OA.

Amplified detection of SARS-COV-2 B.1.1.529 (Omicron) gene oligonucleotides based on exonuclease III-aided MoS2 /AIE nanoprobes.

The coronavirus disease-2019 pandemic reflects the underdevelopment of point-of-care diagnostic technology. Nuclei acid (NA) detection is the "gold standard" method for the early diagnosis of the B.1.1.529 (Omicron) variant of severe acute respiratory syndrome-coronavirus disease-2. Polymerase chain reaction is the main method for NA detection but requires considerable manpower and sample processing taking ≥ 3 h. To simplify the operation processes and reduce the detection time, exonuclease III (Exo III)-aided MoS2 /AIE nanoprobes were developed for rapid and sensitive detection of the oligonucleotides of Omicron. Molybdenum disulfide (MoS2 ) nanosheets with excellent optical absorbance and distinguishable affinity to single-strand and duplex DNAs were applied as quenchers, and aggregation-induced emission (AIE) molecules with high luminous efficiency were designed as donor in fluorescence resonance energy transfer-based nanoprobes. Exo III with catalytic capability was used for signal amplification to increase the sensitivity of detection. The composite nanoprobes detected the mutated nucleocapsid (N)-gene and spike (S)-gene oligonucleotides of Omicron within 40 min with a limit of detection of 4.7 pM, and showed great potential for application in community medicine.

Adapting a Clinical Practice Guideline for Management of Patients with Knee and Hip Osteoarthritis by Hong Kong Physiotherapists.

Knee and hip osteoarthritis are common disabling conditions globally. Although numerous international clinical practice guidelines exist to guide physiotherapy management, not all recommendations issued from these guidelines can be translated to other contexts without considering the cultural acceptability and clinical implementability of targeted countries. Because the ADAPTE framework provides a robust methodology to adapt guidelines to the local context, this study used its methodology to adapt high-quality guideline recommendations to promote optimal physiotherapy care for knee and hip osteoarthritis in Hong Kong. The ADAPTE framework was used and modified to complete the adaptation process. International clinical practice guidelines were identified from eight guideline clearinghouses and six electronic databases. Two independent reviewers critically appraised the eligible guidelines using the AGREE II tool. We extracted and tabulated recommendations from high-quality guidelines. A voting-based consensus among interdisciplinary experts was conducted to decide on suitable recommendations for the Hong Kong context and whether there was a need to modify them. Pertinent recommendations were then translated into the traditional Chinese language. Our team members suggested modifying four tools and adding one to explore the patient's feedback on the recommendations, to the ADAPTE framework. The adaptation was performed on three high-quality guidelines. We adapted 28 and 20 recommendations for treating knee and hip osteoarthritis, respectively. We recommend a multimodal treatment for managing knee and hip osteoarthritis. Land- and aquatic-based exercises, patient education, and self-management were strongly recommended for patients with knee osteoarthritis. Land- and aquatic-based exercises were strongly recommended for patients with hip osteoarthritis. This is the first adaptation study in Hong Kong. It provides guidance to local physiotherapists on managing patients with knee and hip osteoarthritis. Future studies should test the effectiveness of implementing this adapted guideline to improve local physiotherapy care in Hong Kong.

Nanomanipulation of Ligand Nanogeometry Modulates Integrin/Clathrin-Mediated Adhesion and Endocytosis of Stem Cells.

Nanosubstrate engineering can be a biomechanical approach for modulating stem cell differentiation in tissue engineering. However, the study of the effect of clathrin-mediated processes on manipulating this behavior is unexplored. Herein, we develop integrin-binding nanosubstrates with confined nanogeometries that regulate clathrin-mediated adhesion- or endocytosis-active signaling pathways for modulating stem fates. Isotropically presenting ligands on the nanoscale enhances the expression of clathrin in cells, thereby facilitating uptake of dexamethasone-loaded nanoparticles (NPs) to boost osteogenesis of stem cells. In contrast, anisotropic ligand nanogeometry suppresses this clathrin-mediated NP entry by strengthening the association between clathrin and adhesion spots to reinforce mechanotransduced signaling, which can be abrogated by the pharmacological inhibition of clathrin. Meanwhile, inhibiting focal adhesion formation hinders cell spreading and enables a higher endocytosis efficiency. Our findings reveal the crucial roles of clathrin in both endocytosis and mechanotransduction of stem cells and provide the parameter of ligand nanogeometry for the rational design of biomaterials for tissue engineering.

Engineered biochemical cues of regenerative biomaterials to enhance endogenous stem/progenitor cells (ESPCs)-mediated articular cartilage repair.

As a highly specialized shock-absorbing connective tissue, articular cartilage (AC) has very limited self-repair capacity after traumatic injuries, posing a heavy socioeconomic burden. Common clinical therapies for small- to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies, including microfracture, mosaicplasty, autologous chondrocyte implantation (ACI), and matrix-induced ACI (MACI). However, these treatments frequently result in mechanically inferior fibrocartilage, low cost-effectiveness, donor site morbidity, and short-term durability. It prompts an urgent need for innovative approaches to pattern a pro-regenerative microenvironment and yield hyaline-like cartilage with similar biomechanical and biochemical properties as healthy native AC. Acellular regenerative biomaterials can create a favorable local environment for AC repair without causing relevant regulatory and scientific concerns from cell-based treatments. A deeper understanding of the mechanism of endogenous cartilage healing is furthering the (bio)design and application of these scaffolds. Currently, the utilization of regenerative biomaterials to magnify the repairing effect of joint-resident endogenous stem/progenitor cells (ESPCs) presents an evolving improvement for cartilage repair. This review starts by briefly summarizing the current understanding of endogenous AC repair and the vital roles of ESPCs and chemoattractants for cartilage regeneration. Then several intrinsic hurdles for regenerative biomaterials-based AC repair are discussed. The recent advances in novel (bio)design and application regarding regenerative biomaterials with favorable biochemical cues to provide an instructive extracellular microenvironment and to guide the ESPCs (e.g. adhesion, migration, proliferation, differentiation, matrix production, and remodeling) for cartilage repair are summarized. Finally, this review outlines the future directions of engineering the next-generation regenerative biomaterials toward ultimate clinical translation.

Captopril Alleviates Chondrocyte Senescence in DOCA-Salt Hypertensive Rats Associated with Gut Microbiome Alteration.

Gut microbiota is the key controller of healthy aging. Hypertension and osteoarthritis (OA) are two frequently co-existing age-related pathologies in older adults. Both are associated with gut microbiota dysbiosis. Hereby, we explore gut microbiome alteration in the Deoxycorticosterone acetate (DOCA)-induced hypertensive rat model. Captopril, an anti-hypertensive medicine, was chosen to attenuate joint damage. Knee joints were harvested for radiological and histological examination; meanwhile, fecal samples were collected for 16S rRNA and shotgun sequencing. The 16S rRNA data was annotated using Qiime 2 v2019.10, while metagenomic data was functionally profiled with HUMAnN 2.0 database. Differential abundance analyses were adopted to identify the significant bacterial genera and pathways from the gut microbiota. DOCA-induced hypertension induced p16INK4a+ senescent cells (SnCs) accumulation not only in the aorta and kidney (p < 0.05) but also knee joint, which contributed to articular cartilage degradation and subchondral bone disturbance. Captopril removed the p16INK4a + SnCs from different organs, partially lowered blood pressure, and mitigated cartilage damage. Meanwhile, these alterations were found to associate with the reduction of Escherichia-Shigella levels in the gut microbiome. As such, gut microbiota dysbiosis might emerge as a metabolic link in chondrocyte senescence induced by DOCA-triggered hypertension. The underlying molecular mechanism warrants further investigation.

Hybrid composites with magnesium-containing glycosaminoglycans as a chondroconducive matrix for osteoarthritic cartilage repair.

The alteration of the extracellular matrix (ECM) homeostasis plays an important role in the development of osteoarthritis (OA). The pathological changes of OA are mainly manifested in the large reduction of components in ECM, like type II collagen and aggrecan, especially hyaluronic acid and chondroitin sulfate and often accompanied by inflammation. Rebuilding ECM and inhibiting inflammation may reverse OA progression. In this work, we developed new magnesium-containing glycosaminoglycans (Mg-GAGs), to create a positive ECM condition for promoting cartilage regeneration and alleviating OA. In vitro results suggested that the introduction of Mg-GAGs contributed to promoting chondrocyte proliferation and facilitated upregulating chondrogenic genes and suppressed inflammation-related factors. Moreover, Mg-GAGs exhibited positive effects on suppressing synovial inflammation, reducing chondrocyte apoptosis and preserving the subchondral bone in the ACLT-induced OA rabbit model. This study provides new insight into ECM-based therapeutic strategy and opens a new avenue for the development of novel OA treatment.

Biomimicking design of artificial periosteum for promoting bone healing.

Background: Periosteum is a vascularized tissue membrane covering the bone surface and plays a decisive role in bone reconstruction process after fracture. Various artificial periosteum has been developed to assist the allografts or bionic bone scaffolds in accelerating bone healing. Recently, the biomimicking design of artificial periosteum has attracted increasing attention due to the recapitulation of the natural extracellular microenvironment of the periosteum and has presented unique capacity to modulate the cell fates and ultimately enhance the bone formation and improve neovascularization. Methods: A systematic literature search is performed and relevant findings in biomimicking design of artificial periosteum have been reviewed and cited. Results: We give a systematical overview of current development of biomimicking design of artificial periosteum. We first summarize the universal strategies for designing biomimicking artificial periosteum including biochemical biomimicry and biophysical biomimicry aspects. We then discuss three types of novel versatile biomimicking artificial periosteum including physical-chemical combined artificial periosteum, heterogeneous structured biomimicking periosteum, and healing phase-targeting biomimicking periosteum. Finally, we comment on the potential implications and prospects in the future design of biomimicking artificial periosteum. Conclusion: This review summarizes the preparation strategies of biomimicking artificial periosteum in recent years with a discussion of material selection, animal model adoption, biophysical and biochemical cues to regulate the cell fates as well as three types of latest developed versatile biomimicking artificial periosteum. In future, integration of innervation, osteochondral regeneration, and osteoimmunomodulation, should be taken into consideration when fabricating multifunctional artificial periosteum.The Translational Potential of this Article: This study provides a holistic view on the design strategy and the therapeutic potential of biomimicking artificial periosteum to promote bone healing. It is hoped to open a new avenue of artificial periosteum design with biomimicking considerations and reposition of the current strategy for accelerated bone healing.

Chondrocyte-specific genomic editing enabled by hybrid exosomes for osteoarthritis treatment.

Rationale: A cell-specific delivery vehicle is required to achieve gene editing of the disease-associated cells, so the hereditable genome editing reactions are confined within these cells without affecting healthy cells. A hybrid exosome-based nano-sized delivery vehicle derived by fusion of engineered exosomes and liposomes will be able to encapsulate and deliver CRISPR/Cas9 plasmids selectively to chondrocytes embedded in articular cartilage and attenuate the condition of cartilage damage. Methods: Chondrocyte-targeting exosomes (CAP-Exo) were constructed by genetically fusing a chondrocyte affinity peptide (CAP) at the N-terminus of the exosomal surface protein Lamp2b. Membrane fusion of the CAP-Exo with liposomes formed hybrid CAP-exosomes (hybrid CAP-Exo) which were used to encapsulate CRISPR/Cas9 plasmids. By intra-articular (IA) administration, hybrid CAP-Exo/Cas9 sgMMP-13 entered the chondrocytes of rats with cartilage damages that mimicked the condition of osteoarthritis. Results: The hybrid CAP-Exo entered the deep region of the cartilage matrix in arthritic rats on IA administration, delivered the plasmid Cas9 sgMMP-13 to chondrocytes, knocked down the matrix metalloproteinase 13 (MMP-13), efficiently ablated the expression of MMP-13 in chondrocytes, and attenuated the hydrolytic degradation of the extracellular matrix proteins in the cartilage. Conclusion: Chondrocyte-specific knockdown of MMP-13 mitigates or prevents cartilage degradation in arthritic rats, showing that hybrid CAP-Exo/Cas9 sgMMP-13 may alleviate osteoarthritis.

Development of human cartilage circadian rhythm in a stem cell-chondrogenesis model.

The circadian clock in murine articular cartilage is a critical temporal regulatory mechanism for tissue homeostasis and osteoarthritis. However, translation of these findings into humans has been hampered by the difficulty in obtaining circadian time series human cartilage tissues. As such, a suitable model is needed to understand the initiation and regulation of circadian rhythms in human cartilage. Methods: We used a chondrogenic differentiation protocol on human embryonic stem cells (hESCs) as a proxy for early human chondrocyte development. Chondrogenesis was validated using histology and expression of pluripotency and differentiation markers. The molecular circadian clock was tracked in real time by lentiviral transduction of human clock gene luciferase reporters. Differentiation-coupled gene expression was assessed by RNAseq and differential expression analysis. Results: hESCs lacked functional circadian rhythms in clock gene expression. During chondrogenic differentiation, there was an expected reduction of pluripotency markers (e.g., NANOG and OCT4) and a significant increase of chondrogenic genes (SOX9, COL2A1 and ACAN). Histology of the 3D cartilage pellets at day 21 showed a matrix architecture resembling human cartilage, with readily detectable core clock proteins (BMAL1, CLOCK and PER2). Importantly, the circadian clocks in differentiating hESCs were activated between day 11 (end of the 2D stage) and day 21 (10 days after 3D differentiation) in the chondrogenic differentiation protocol. RNA sequencing revealed striking differentiation coupled changes in the expression levels of most clock genes and a range of clock regulators. Conclusions: The circadian clock is gradually activated through a differentiation-coupled mechanism in a human chondrogenesis model. These findings provide a human 3D chondrogenic model to investigate the role of the circadian clock during normal homeostasis and in diseases such as osteoarthritis.

Association between hypertension and osteoarthritis: A systematic review and meta-analysis of observational studies.

Objective: Literature examining the relationship between elevated blood pressure and osteoarthritis (OA) has yielded conflicting results. This study aimed to systematically review the relationship between hypertension and OA in both load-bearing and non-load-bearing joints. Methods: A systematic literature search was performed on Embase, Emcare, MEDLINE and Ovid Nursing Database. The associations between hypertension and OA development in knees, hips and hands were analysed by calculating the odds ratio (OR). Results: A total of 26 studies with 97,960 participants were included. The overall odds of having OA significantly increased in the people with hypertension compared to the normotensive ones (OR â€‹= â€‹1.60, 95%CI â€‹= â€‹1.33, 1.94). The association of hypertension with OA was detected in knee (OR â€‹= â€‹1.62, 95%CI â€‹= â€‹1.32, 1.98), not in hand (OR â€‹= â€‹1.19, 95%CI â€‹= â€‹0.92, 1.53). Moreover, there existed a stronger association of hypertension with radiographic knee OA (OR â€‹= â€‹1.89, 95%CI â€‹= â€‹1.40, 2.54) than symptomatic knee OA (OR â€‹= â€‹1.39, 95%CI â€‹= â€‹1.17, 1.65). The association between hypertension and radiographic knee OA remained statistically significant for the studies that adjusted for body mass index (BMI) (OR â€‹= â€‹1.42, 95%CI â€‹= â€‹1.13, 1.78), and was particularly strong in women (OR â€‹= â€‹2.27, 95%CI â€‹= â€‹1.17, 4.39). Conclusion: A BMI-independent association between hypertension and radiographic knee OA existed with potential sex variation, which warrants further investigations into the underlying genetic, hormonal and environmental factors.The translational potential of this article: Blood pressure has been reported to link with OA for years ago, however, its contribution to OA is still unclear and conflicted in different reports. This review indicated an intimate relationship between hypertension and structural damages of knee OA, rather than simply chronic joint pain, especially in women. This finding not only provides stronger support for further investigations into the causal risk factor, i.e. hypertension, of OA from tissue level to molecular level, but also putting forward a novel thinking in OA pathogenesis and its therapy strategies. Orthopedic translation: This study further strengthen the association between hypertension and radiographic knee OA. It points in a vascular aetiology hypothesis of OA. It might open up a new avenue for repositioning anti-hypertensive medications for osteoarthritis treatment.

Artificial intelligence in diagnosis of knee osteoarthritis and prediction of arthroplasty outcomes: a review.

BACKGROUND: Artificial intelligence is an emerging technology with rapid growth and increasing applications in orthopaedics. This study aimed to summarize the existing evidence and recent developments of artificial intelligence in diagnosing knee osteoarthritis and predicting outcomes of total knee arthroplasty. METHODS: PubMed and EMBASE databases were searched for articles published in peer-reviewed journals between January 1, 2010 and May 31, 2021. The terms included: 'artificial intelligence', 'machine learning', 'knee', 'osteoarthritis', and 'arthroplasty'. We selected studies focusing on the use of AI in diagnosis of knee osteoarthritis, prediction of the need for total knee arthroplasty, and prediction of outcomes of total knee arthroplasty. Non-English language articles and articles with no English translation were excluded. A reviewer screened the articles for the relevance to the research questions and strength of evidence. RESULTS: Machine learning models demonstrated promising results for automatic grading of knee radiographs and predicting the need for total knee arthroplasty. The artificial intelligence algorithms could predict postoperative outcomes regarding patient-reported outcome measures, patient satisfaction and short-term complications. Important weaknesses of current artificial intelligence algorithms included the lack of external validation, the limitations of inherent biases in clinical data, the requirement of large datasets in training, and significant research gaps in the literature. CONCLUSIONS: Artificial intelligence offers a promising solution to improve detection and management of knee osteoarthritis. Further research to overcome the weaknesses of machine learning models may enhance reliability and allow for future use in routine healthcare settings.

COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives.

COVID-19 is a trending topic worldwide due to its immense impact on society. Recent trends have shifted from acute effects towards the long-term morbidity of COVID-19. In this review, we hypothesize that SARS-CoV-2 contributes to age-related perturbations in endothelial and adipose tissue, which are known to characterize the early aging process. This would explain the long-lasting symptoms of SARS-CoV-2 as the result of an accelerated aging process. Connective tissues such as adipose tissue and musculoskeletal tissue are the primary sites of aging. Therefore, current literature was analyzed focusing on the musculoskeletal symptoms in COVID-19 patients. Hypovitaminosis D, increased fragility, and calcium deficiency point towards bone aging, while joint and muscle pain are typical for joint and muscle aging, respectively. These characteristics could be classified as early osteoarthritis-like phenotype. Exploration of the impact of SARS-CoV-2 and osteoarthritis on endothelial and adipose tissue, as well as neuronal function, showed similar perturbations. At a molecular level, this could be attributed to the angiotensin-converting enzyme 2 expression, renin-angiotensin system dysfunction, and inflammation. Finally, the influence of the nicotinic cholinergic system is being evaluated as a new treatment strategy. This is combined with the current knowledge of musculoskeletal aging to pave the road towards the treatment of long-term COVID-19.