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Chiew Yong Ng,1 Jia Ying Chai,1 Jhi Biau Foo,2,3 Nor Hamdan Mohamad Yahaya,4 Ying Yang,5 Min Hwei Ng,1 Jia Xian Law1 1Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, 56000, Malaysia; 2School of Pharmacy, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, 47500, Selangor, Malaysia; 3Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, Selangor, 47500, Malaysia; 4Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, Malaysia; 5School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent, ST4 7QB, UKCorrespondence: Jia Xian LawCentre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, Kuala Lumpur, 56000, MalaysiaTel +603 9145 7677Fax +603 9145 7678Email danieljx08@gmail.com; lawjx@ppukm.ukm.edu.myAbstract: Treatment of cartilage defects such as osteoarthritis (OA) and osteochondral defect (OCD) remains a huge clinical challenge in orthopedics. OA is one of the most common chronic health conditions and is mainly characterized by the degeneration of articular cartilage, shown in the limited capacity for intrinsic repair. OCD refers to the focal defects affecting cartilage and the underlying bone. The current OA and OCD management modalities focus on symptom control and on improving joint functionality and the patient’s quality of life. Cell-based therapy has been evaluated for managing OA and OCD, and its chondroprotective efficacy is recognized mainly through paracrine action. Hence, there is growing interest in exploiting extracellular vesicles to induce cartilage regeneration. In this review, we explore the in vivo evidence of exosomes on cartilage regeneration. A total of 29 in vivo studies from the PubMed and Scopus databases were identified and analyzed. The studies reported promising results in terms of in vivo exosome delivery and uptake; improved cartilage morphological, histological, and biochemical outcomes; enhanced subchondral bone regeneration; and improved pain behavior following exosome treatment. In addition, exosome therapy is safe, as the included studies documented no significant complications. Modifying exosomal cargos further increased the cartilage and subchondral bone regeneration capacity of exosomes. We conclude that exosome administration is a potent cell-free therapy for alleviating OA and OCD. However, additional studies are needed to confirm the therapeutic potential of exosomes and to identify the standard protocol for exosome-based therapy in OA and OCD management.Keywords: extracellular vesicle, exosome, chondrocyte, cartilage, osteoarthritis

Transient osteoporosis of the hip (TOH) during pregnancy is a rare, self-limiting condition that frequently goes undiagnosed. However, if not managed properly, TOH can lead to significant complications, such as pathological fractures. We report a case of a 29-year-old primigravida at 33 weeks and four days of gestation who presented with a right femoral neck fracture following a fall. She had experienced prodromal hip pain for one month, initially misdiagnosed as pelvic girdle pain. Radiological evaluation revealed osteopenia and a sub-capital femoral neck fracture. Blood investigations were unremarkable. During hospitalisation, the patient was also diagnosed with asymptomatic COVID-19 infection, complicating the management approach. A multidisciplinary team decided on an elective caesarean section followed by closed manipulative reduction (CMR) and percutaneous screw fixation. Therefore, TOH in pregnancy requires timely diagnosis and intervention to prevent complications such as fractures. In cases complicated by concurrent conditions like COVID-19, multidisciplinary management is essential to ensure optimal outcomes for both mother and child., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tan et al.)

Prosthetic joint infection (PJI) is a catastrophic complication in total knee arthroplasty (TKA). Implant retention with eradication of infection to maintain limb function is ideal and debridement, antibiotics, and implant retention (DAIR) have been reported to have variable success rates depending on several factors, including the duration of infection, the host immunity, the virulence of the causative microorganism, and the technique employed. In this case series, we present a series of successful cases presented with PJI after TKA and were treated using DAIR either via impregnation of vancomycin beads or calcium sulfate beads (antibiotic stimulan)., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Abdull Sitar et al.)

Pulmonary embolism (PE) is a life-threatening condition that occurs due to the blockage of the pulmonary artery by blood clots. The occurrence of PE after total knee arthroplasty (TKA) is quite rare. Individuals with a history of PE have a high risk of recurrent venous thromboembolism (VTE). We have encountered a case of saddle PE (SPE) following TKA. The patient underwent a TKA due to advanced osteoarthritis. She started to develop respiratory distress after day 2 of surgery. Further investigation showed that she developed SPE. The conclusion from this case is that, while the occurrence is rare, it is critical to identify the risk factors for each patient prior to surgery. Individuals with VTE are at risk of developing recurrent VTE. Those with a previous history of VTE may require long-term anticoagulant medication to prevent a recurrence. Early diagnosis of the risk factor for VTE before the surgical procedure helps assure a positive outcome and prognosis following the procedure. As an additional benefit, it will lower the rates of perioperative morbidity and mortality., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Abdul Halim et al.)

Extra-articular deformities (EAD) can pose a challenge to surgeons during a total knee arthroplasty (TKA) surgery. Obtaining an acceptable post-operative hip-knee-ankle (HKA) angle may be difficult, especially in a limb with multiplanar deformities of both the femur and the tibia.  Our case is about a 66-year-old gentleman with a long-term deformity of his right lower limb secondary to malunion of the right femoral shaft and tibial shaft fractures. He initially presented with a right floating knee injury, 45 years ago, which was managed with conservative measures. He subsequently presented to us with ipsilateral knee osteoarthritis and underwent a robotic-assisted total knee arthroplasty surgery. Robotic- or computer-assisted total knee arthroplasty is an actively developing area and is gaining popularity among arthroplasty surgeons. In cases with severe extra-articular deformities such as in this case, robotic-assisted surgery can be superior to conventional surgery., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Matheen et al.)

Resilience increases the ability of an individual to overcome adversity. It has not yet been determined how resilience is linked to quality of life among individuals experiencing knee osteoarthritis symptoms. To explore the inter-relationships of psychological distress, resilience and quality of life among older individuals with knee osteoarthritis. The study examined older adults in Kuala Lumpur and Selangor, identifying osteoarthritis through verified physician diagnosis. Various factors, including resilience, psychological status, and quality of life, were measured. In the study with 338 older adults, 50.9% had knee osteoarthritis. Higher resilience was linked to lower depression, anxiety, and stress, and better quality of life in both groups with and without knee osteoarthritis. Psychological factors consistently mediated the link between resilience and quality of life even after controlling potential confounders. Analysis showed that depression, anxiety, and stress mediate the relationship between resilience and quality of life, indicating a significant influence even when considering various factors. Resilience appears to influence psychological well-being and quality of life among older adult with knee osteoarthritis.

Robotic-assisted hip and knee arthroplasty represents cutting-edge advancements in orthopedic surgery, harnessing robotic technology to enhance precision, improve clinical outcomes, and facilitate intra-operative procedures. In these robotic-assisted surgeries, the robotic systems assist surgeons in planning and executing joint replacement surgeries, thereby facilitating personalized implant positioning and optimizing the fit and alignment of hip and knee implants. Despite the increasing attention garnered by robotic-assisted hip and knee arthroplasty in recent years, a comprehensive bibliometric analysis using the Scopus database has yet to be conducted. This bibliometric analysis reviews the Scopus database from 1961 until 2022 to investigate the literature on the field of robotic-assisted hip and knee arthroplasty. A total of 577 articles that satisfied the selection criteria were included in this review. The majority of the articles focus more on total knee replacement, compared to total hip replacement and unicompartmental knee arthroplasty. The overwhelming majority of the articles were authored by researchers and clinicians from the United States of America (USA) and the United Kingdom (UK). Similarly, most of the articles with the highest number of citations were authored by researchers and clinicians from these regions. This comprehensive bibliometric analysis using Scopus in the domain of robotic-assisted hip and knee replacement has the potential to act as a roadmap for researchers, clinicians, and policymakers, facilitating informed decision-making, promoting collaborative initiatives, and guiding the development of future studies to further advance the field of robotic-assisted hip and knee arthroplasty., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kow et al.)

Background: The study sought to understand the self-management strategies used by patients during the postponement of their total knee arthroplasty (TKA) procedure, as well as the associations between the length of waiting time, pain, and physical frailty and function. The study focused on individuals aged 50 years and above, as they are known to be more vulnerable to the negative impacts of delayed elective surgery and rehabilitation. This study hypothesizes that delayed TKR due to coronavirus disease 2019 (COVID-19) will bear negative effect in self-management, pain, and physical frailty and function in older adults., Aim: To investigate the effects of COVID-19 pandemic on self-management, pain, and physical function in older adults awaiting TKA in Malaysia., Methods: This cross-sectional study has the data of participants, who matched the criteria and scheduled for TKA for the first time, extracted from the TKA registry in the Department of Orthopaedics and Traumatology, Hospital Canselor Tuanku Mukhriz. Data on pain status, and self-management, physical frailty, and instrumental activities daily living were also collected. Multiple linear regression analysis with a significant level of 0.05 was used to identify the association between waiting time and pain on physical frailty and functional performance., Results: Out of 180 had deferred TKA, 50% of them aged 50 years old and above, 80% were women with ethnic distribution Malay (66%), Chinese (22%), Indian (10%), and others (2%) respectively. Ninety-two percent of the participants took medication to manage their pain during the waiting time, while 10% used herbs and traditional supplements, and 68% did exercises as part of their osteoarthritis (OA) self-management. Thirty-six participants were found to have physical frailty (strength, assistance with walking, rising from a chair, climbing stairs, and falls questionnaire score > 4) which accounted for 72%. Increased pain was associated with physical frailty with odds ratio, odds ratio (95% confidence interval): 1.46 (1.04-2.05). This association remained significant even after the adjustment according to age and self-management., Conclusion: While deferring TKA during a pandemic is unavoidable, patient monitoring for OA treatment during the waiting period is important in reducing physical frailty, ensuring the older patients' independence., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The use of gelatin microspheres (GMs) as a cell carrier has been extensively researched. One of its limitations is that it dissolves rapidly in aqueous settings, precluding its use for long-term cell propagation. This circumstance necessitates the use of crosslinking agents to circumvent the constraint. Thus, this study examines two different methods of crosslinking and their effect on the microsphere's physicochemical and cartilage tissue regeneration capacity. Crosslinking was accomplished by physical (dehydrothermal [DHT]) and natural (genipin) crosslinking of the three-dimensional (3D) GM. We begin by comparing the microstructures of the scaffolds and their long-term resistance to degradation under physiological conditions (in an isotonic solution, at 37°C, pH = 7.4). Infrared spectroscopy indicated that the gelatin structure was preserved after the crosslinking treatments. The crosslinked GM demonstrated good cell adhesion, viability, proliferation, and widespread 3D scaffold colonization when seeded with human bone marrow mesenchymal stem cells. In addition, the crosslinked microspheres enhanced chondrogenesis, as demonstrated by the data. It was discovered that crosslinked GM increased the expression of cartilage-related genes and the biosynthesis of a glycosaminoglycan-positive matrix as compared with non-crosslinked GM. In comparison, DHT-crosslinked results were significantly enhanced. To summarize, DHT treatment was found to be a superior approach for crosslinking the GM to promote better cartilage tissue regeneration.

Background: The 2013 Malaysian Clinical Practice Guidelines on the Management of Osteoarthritis (OA) recommend a linear step-up approach to manage knee OA. However, patients with knee OA often require a multimodal approach to address OA-related pain symptoms and functional limitations. This consensus aimed to provide doctors with an updated set of evidence-based, clinical experience-guided recommendations to manage knee OA., Methods: A multi-speciality expert panel consisting of nine Malaysian physicians from different healthcare settings who manage a diverse OA patient population was convened. Using a combination of the ADAPTE process and modified Delphi method, the panel reviewed current evidence on the management of knee OA and synthesised a set of nine recommendations on the management of knee OA, supported by an algorithm that summarises the consensus' core messages., Results: A multimodal intervention strategy is the mainstay of OA management and the choice of any single or multimodal intervention may vary over the course of the disease. Overall, a non-pharmacological core treatment set of patient education, weight loss and exercise is recommended for all patients. When pharmacotherapy is indicated, symptomatic slow-acting drugs for osteoarthritis are recommended at the early stage of disease, and they can be paired with physical therapy as background treatment. Concurrent advanced pharmacotherapy that includes non-steroidal anti-inflammatory drugs, intraarticular injections and short-term weak opioids can be considered if patients do not respond sufficiently to background treatment. Patients with severe symptomatic knee OA should be considered for knee replacement surgery. Management should begin with specific treatments with the least systemic exposure or toxicity, and the choice of treatment should be determined as a shared decision between patients and their team of healthcare providers., Conclusions: This consensus presents nine recommendations that advocate an algorithmic approach in the management of patients living with knee OA. They are applicable to patients receiving treatment from primary to tertiary care providers in Malaysia as well as other countries.

Background and Objective: To evaluate the ability of anaesthetic trainee doctors compared to nursing anaesthetic assistants in identifying the cricoid cartilage, applying the appropriate cricoid pressure and producing an adequate laryngeal inlet view., Methods: Eighty-five participants, 42 anaesthetic trainee doctors and 43 nursing anaesthetic assistants, were asked to complete a set of questionnaires which included the correct amount of force to be applied to the cricoid cartilage. They were then asked to identify the cricoid cartilage and apply the cricoid pressure on an upper airway manikin placed on a weighing scale, and the pressure was recorded. Subsequently they applied cricoid pressure on actual anaesthetized patients following rapid sequence induction. Details regarding the cricoid pressure application and the Cormack-Lehane classification of the laryngeal view were recorded., Results: The anaesthetic trainee doctors were significantly better than the nursing anaesthetic assistants in identifying the cricoid cartilage (95.2% vs. 55.8%, p=0.001). However, both groups were equally poor in the knowledge about the amount of cricoid pressure force required (11.9% vs. 9.3% respectively) and in the correct application of cricoid pressure (16.7% vs. 20.9% respectively). The three-finger technique was performed by 85.7% of the anaesthetic trainee doctors and 65.1% of the nursing anaesthetic assistants (p=0.03). There were no significant differences in the Cormack-Lehane view between both groups., Conclusion: The anaesthetic trainee doctors were better than the nursing anaesthetic assistants in cricoid cartilage identification but both groups were equally poor in their knowledge and application of cricoid pressure., (Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Objective: Functional tissue engineering has emerged as a potential means for treatment of cartilage defect. Development of a stable cartilage composite is considered to be a good option. The aim of the study was to observe whether the incorporation of cultured chondrocytes on porous tantalum utilizing fibrin as a cell carrier would promote cartilage tissue formation., Methods: Rabbit articular chondrocytes were cultured and seeded onto tantalum with fibrin as temporary matrix in a composite, which was divided into three groups. The first group was kept in vitro while a total of 12 constructs were implanted into the dorsum of mice for the second and third groups. The implanted tissues were harvested after 4 weeks (second group) and after 8 weeks (third group). Specific characteristic of cartilage growth were studied by histological and biochemical assessment, immunohistochemistry, and quantitative PCR analysis., Results: Histological and biochemical evaluation of the formed cartilage using hematoxylin and eosin and Alcian blue staining showed lacunae chondrocytes embedded in the proteoglycan rich matrix. Dimethylmethylene blue assay demonstrated high glycosaminoglycans content in the removed tissue following 8 weeks of implantation. Immunohistochemistry results showed the composites after implantation expressed high collagen type II. Quantitative PCR results confirmed a significant increase in cartilage associated genes expression (collagen type II, AggC, Sox 9) after implantation., Conclusion: Tantalum scaffold with fibrin as cell carrier promotes chondrocyte proliferation and cartilaginous tissue formation. Producing hyaline cartilage within a stable construct of tantalum and fibrin has a potential for treatment of cartilage defect.

Background Aims: The use of retropatellar fat pad-derived mesenchymal stromal cells (RFMSCs) for cell-based therapy, particularly for cartilage repair, has been reported by several investigators in recent years. However, the effects of the donor's age and medical condition on the characteristics of RFMSCs have not been well established. The aim of this study was to determine whether age and medical condition can reduce the multipotential of stem cells isolated from the retropatellar fat pad., Methods: The RFMSCs were isolated from patients with osteoarthritic knee cartilage (degenerative group; 40-60 years old) and compared with patients without degenerative knee disease (young group; <40 years old) in terms of their growth kinetics, immunophenotype, differentiation ability and stemness gene expression., Results: Data showed that RFMSCs from both groups have similar growth kinetics and immunophenotype profile at passage 3. However, RFMSCs from the degenerative group showed lower adipogenic, osteogenic and chondrogenic differentiation ability compared with RFMSCs derived from the young group. The stemness gene expression level of RFMSCs derived from the degenerative group was lower than that in the young group. RFMSCs from both groups met the minimum criteria of mesenchymal stromal cells and have the potential for cartilage regeneration. However, RFMSCs from the degenerative group showed lower regeneration capability., Conclusions: These results indicate that older age and osteoarthritic condition did affect the multipotential of stem cells derived from the retropatellar fat pad under the current prescribed condition. More studies will be conducted to clarify whether the age or medical condition contributed more to the loss of differentiation capacity and stemness gene expression of RFMSCs., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Osteoarthritis (OA) is a degenerative joint disease that results in the destruction of cartilage. Edible Bird's Nest (EBN) extract contains important components, which can reduce the progression of osteoarthritis and helps in the regeneration of the cartilage. The present study aimed to investigate the effect of EBN extract on the catabolic and anabolic activities of the human articular chondrocytes (HACs) isolated from the knee joint of patients with OA., Methods: A single batch of EBN extract was prepared with hot-water extraction and coded as HMG. HACs were isolated from the knee joint cartilage removed during surgery. The optimum concentration of HMG for HAC cultures was determined using MTT assay. The effect of HMG on the catabolic and anabolic genes' expression in HACs was measured by real-time PCR. The total amount of prostaglandin E2 (PGE2) production was determined by ELISA method, and the total sulphated glycosaminoglycan (GAGs) production was quantified by 1,9-dimethylmethylene blue (DMMB) assay., Results: MTT assay showed 0.50% - 1.00% HMG supplementation promoted HACs proliferation. HMG supplementation was able to reduce the catabolic genes' expression in cultured HACs such as matrix metalloproteinases (MMP1 & MMP3), Interleukin 1, 6 and 8 (IL-1, IL-6 & IL-8), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Prostaglandin E2 (PGE2) production was significantly reduced in HAC cultures supplemented with HMG. With regard to anabolic activity assessment, type II collagen, Aggrecan and SOX-9 gene expression as well as sGAG production was increased in the HMG supplemented groups., Conclusion: Edible Bird's Nest extract coded as HMG demonstrated chondro-protection ability on human articular chondrocytes in vitro. It reduced catabolic activities and increased cartilage extracellular matrix synthesis. It is concluded that HMG is a potential agent in the treatment of osteoarthritis.

Aims: The mRNA level for interleukin-6 (IL-6) is an important marker of osteoarthritis (OA). The present study aimed to investigate the level of IL-6 mRNA in the cartilage of OA knee while comparing it to the normal cartilage obtained from the same patient., Materials and Methods: A total of 21 patients who underwent total knee replacement were recruited for this study. Sectioning of the destructive cartilage was performed in the medial part of the proximal tibiofemoral cartilage. The unaffected lateral part of the knee in the same patient, served as a control. The mRNA level for IL-6 was assessed using LightCycler 2.0 quantitative real-time polymerase chain reaction (qRT-PCR). actin mRNA was used as an endogenous control., Results: Twelve out of 21 patients (57.1%) exhibited up regulation of IL-6 mRNA in the OA cartilage as compared to the normal cartilage. The rest of the patients (42.9%) showed down regulation of IL-6 mRNA. The statistical analysis showed there was insignificant level of IL-6 mRNA in the OA (1.91 +/- 0.45) as compared to the normal cartilage (1.13 +/- 0.44) (p > 0.05). The inter-individual variation in the level of IL-6 mRNA in the cartilage of idiopathic knee was in accordance with previous findings., Conclusions: These observations suggest IL-6 could also act as a catabolic agent in some patients or its expression might be influenced by other cytokines.