Intra-articular sustained-release of pirfenidone as a disease-modifying treatment for early osteoarthritis.

Osteoarthritis (OA) is a major clinical challenge, and effective disease-modifying drugs for OA are still lacking due to the complicated pathology and scattered treatment targets. Effective early treatments are urgently needed to prevent OA progression. The excessive amount of transforming growth factor ß (TGFß) is one of the major causes of synovial fibrosis and subchondral bone sclerosis, and such pathogenic changes in early OA precede cartilage damage. Herein we report a novel strategy of intra-articular sustained-release of pirfenidone (PFD), a clinically-approved TGFß inhibitor, to achieve disease-modifying effects on early OA joints. We found that PFD effectively restored the mineralization in the presence of excessive amount of TGFß1 (as those levels found in patients' synovial fluid). A monthly injection strategy was then designed of using poly lactic-co-glycolic acid (PLGA) microparticles and hyaluronic acid (HA) solution to enable a sustained release of PFD (the "PLGA-PFD + HA" strategy). This strategy effectively regulated OA progression in destabilization of the medial meniscus (DMM)- induced OA mice model, including preventing subchondral bone loss in early OA and subchondral bone sclerosis in late OA, and reduced synovitis and pain with cartilage preservation effects. This finding suggests the promising clinical application of PFD as a novel disease-modifying OA drug.

Unsupervised domain adaptation for automated knee osteoarthritis phenotype classification.

Background: Osteoarthritis (OA) is a global healthcare problem. The increasing population of OA patients demands a greater bandwidth of imaging and diagnostics. It is important to provide automatic and objective diagnostic techniques to address this challenge. This study demonstrates the utility of unsupervised domain adaptation (UDA) for automated OA phenotype classification. Methods: We collected 318 and 960 three-dimensional double-echo steady-state magnetic resonance images from the Osteoarthritis Initiative (OAI) dataset as the source dataset for phenotype cartilage/meniscus and subchondral bone, respectively. Fifty three-dimensional turbo spin echo (TSE)/fast spin echo (FSE) MR images from our institute were collected as the target datasets. For each patient, the degree of knee OA was initially graded according to the MRI Knee Osteoarthritis Knee Score before being converted to binary OA phenotype labels. The proposed four-step UDA pipeline included (I) pre-processing, which involved automatic segmentation and region-of-interest cropping; (II) source classifier training, which involved pre-training a convolutional neural network (CNN) encoder for phenotype classification using the source dataset; (III) target encoder adaptation, which involved unsupervised adjustment of the source encoder to the target encoder using both the source and target datasets; and (IV) target classifier validation, which involved statistical analysis of the classification performance evaluated by the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity and accuracy. We compared our model on the target data with the source pre-trained model and the model trained with the target data from scratch. Results: For phenotype cartilage/meniscus, our model has the best performance out of the three models, giving 0.90 [95% confidence interval (CI): 0.79-1.02] of the AUROC score, while the other two model show 0.52 (95% CI: 0.13-0.90) and 0.76 (95% CI: 0.53-0.98). For phenotype subchondral bone, our model gave 0.75 (95% CI: 0.56-0.94) at AUROC, which has a close performance of the source pre-trained model (0.76, 95% CI: 0.55-0.98), and better than the model trained from scratch on the target dataset only (0.53, 95% CI: 0.33-0.73). Conclusions: By utilising a large, high-quality source dataset for training, the proposed UDA approach enhances the performance of automated OA phenotype classification for small target datasets. As a result, our technique enables improved downstream analysis of locally collected datasets with a small sample size.

Surgical accuracy of image-free versus image-based robotic-assisted total knee arthroplasty.

BACKGROUND: This study investigated the accuracy in achieving proper lower limb alignment and component positions after total knee replacement (TKR) with image-free and image-based robotic-assisted TKR. METHODS: A total of 129 patients (166 knees) suffering from end-stage knee arthritis who underwent TKA operated by robotic-assisted surgery between the years 2018 and mid-2021 were recruited. Radiological outcomes were compared between image-free and image-based robotic-assisted surgical systems. RESULTS: There were significant differences between the two robotic systems when comparing the mean planned component alignment and the mean measured alignment on radiographs, in which the image-free robotic-assisted system was more varus, whereas the image-based robotic-assisted system was more valgus for both the mean femoral and tibial component coronal alignment (p < 0.001). For tibial component sagittal alignment, the image-based group had a larger deviation from the planned posterior slope (p < 0.001). CONCLUSION: Image-free and image-based robotic assisted TKR had differing accuracy in femoral and tibial alignment.

Single use Negative Pressure Wound Therapy (NPWT) system in the management of knee arthroplasty.

BACKGROUND: Wound complication, skin blister formation in particular, causes devastating consequences after total knee arthroplasty (TKA). Negative Pressure Wound Therapy (NPWT) tries to improve wound management leading to decrease length of hospital stay and better clinical outcomes. Low body mass index (BMI) could play a part in wound recovery management although lacking evidence. This study compared length of hospital stay and clinical outcomes between NPWT and Conventional groups, and factors affected and how BMI affected. METHODS: This was a retrospective clinical record review of 255 (160 NPWT and 95 Conventional) patients between 2018 and 2022. Patient demographics including body mass index (BMI), surgical details (unilateral or bilateral), length of hospital stay, clinical outcomes including skin blisters occurrence, and major wound complications were investigated. RESULTS: Mean age of patients at surgery was 69.95 (66.3% were female). Patients treated with NPWT stayed significantly longer in the hospital after joint replacement (5.18 days vs. 4.55 days; p = 0.01). Significantly fewer patients treated with NPWT found to have blisters (No blisters: 95.0% vs. 87.4%; p = 0.05). In patients with BMI < 30, percentage of patients requiring dressing change was significantly lower when treated with NPWT than conventional (0.8% vs. 33.3%). CONCLUSION: Percentage of blisters occurrence in patients who underwent joint replacement surgery is significantly lower using NPWT. Patients using NPWT stayed significantly longer in the hospital after surgery because significant proportion received bilateral surgery. NPWT patients with BMI < 30 were significantly less likely to change wound dressing.

Long-term survivorship and results in lower limb arthroplasty: a registry-based comparison study.

INTRODUCTION: Popularity of joint replacement surgery due to ever aging population surges the demand for a proper national joint registry. Our Chinese University of Hong Kong - Prince of Wales Hospital (CUHK-PWH) joint registry has passed the 30th year. The aims of this study are 1) summarize our territory-wide joint registry which has passed the 30th year since establishment and 2) compare our statistics with other major joint registries. METHODS: Part 1 was to review the CUHK-PWH registry. Demographic characteristics of our patients who underwent knee and hip replacements had been summarized. Part 2 was a series of comparisons with registries from Sweden, UK, Australia and New Zealand. RESULTS: CUHK-PWH registry captured 2889 primary total knee replacements (TKR) (110 (3.81%) revision) and 879 primary total hip replacements (THR) (107 (12.17%) revision). Median Surgery time of TKR was shorter than THR. Clinical outcome scores were much improved after surgery in both. Uncemented of hybrid in TKR were most popular in Australia (33.4%) and 40% in Sweden and UK. More than half of TKR and THR patients showed the highest percentage with ASA grade 2. New Zealand reflected the best cumulative percentage survival 20 years after surgery of 92.2%, 76.0%, 84.2% survivorship 20 years after TKR, unicompartmental knee replacement (UKR) and Hip. CONCLUSION: A worldwide accepted patient-reported outcome measure (PROM) is recommended to develop to make comparisons among registries and studies feasible. Completeness of registry data is important and useful to improve surgical performance through data comparisons from different regions. Funding from government on sustaining registries is reflected. Registries from Asian countries have yet to be grown and reported.

Surgical accuracy and clinical outcomes of image-free robotic-assisted total knee arthroplasty.

BACKGROUND: The development of total knee arthroplasty (TKA) for knee osteoarthritis (OA) has a good reputation for its effectiveness in reducing joint pain and improving range of motion. We aimed to review our early results using the image-free robotic-assisted technology in knee arthroplasty. METHODS: A total of 71 patients suffering from end-stage OA knee receiving TKA operated by robotic-assisted surgery between the years 2018 and mid-2021 were recruited. Clinical and radiological outcomes were compared with age and sex-matched control group (conventional TKA). RESULTS: The radiological outcome showed significantly more postoperative lower limb alignment outliers in conventional side than robotic-assisted sides. Postoperative knee scores were similar among both groups. Robotic-assisted TKA required a longer implantation time but a shorter hospital stay. CONCLUSION: Robotic-assisted TKA achieved a lower rate of mechanical axis Outlier in the coronal and sagittal plane with a shorter hospital stay. Yet both methods achieve a similar functional outcome.

Randomized control trial of mesenchymal stem cells versus hyaluronic acid in patients with knee osteoarthritis - A Hong Kong pilot study.

Objective: This pilot study evaluated the efficacy of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) versus hyaluronic acid (HA) in surgically naïve patients with knee osteoarthritis (OA). Methods: Single-centre, single-blind randomized study of patients with knee OA. Twenty patients were randomized into groups of 10 each for intra-articular injection of cultured BM-MSCs (6 â€‹ml of BM-MSCs at 1 â€‹× â€‹106 â€‹cells/mL) or HA (6 â€‹ml). Clinical assessments of pain, quality of life, radiographic imaging, and magnetic resonance imaging (MRI) compositional change were performed at baseline and 12 months follow-up. Results: Compared with HA, BM-MSCs injection resulted in significant improvement in qualify of life and reduction in pain as reflected by visual analogue scale (VAS) pain score, Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and 36-Item Short Form Survey (SF-36) score collectively. T2-relaxation time tended to decrease more in the BM-MSCs group with a 38 â€‹± â€‹24.0% reduction in 6 out of 10 BM-MSC participants; while there was only a 12 â€‹± â€‹7.9% reduction in 4 out of 10 HA participants at the end of follow-up. The remaining participants showed either no response or had relaxation time increased on MRI assessment. Conclusions: This pilot study found that autologous BM-MSCs significantly reduced pain, improved functional assessment score, and improved quality of life parameters comparing with HA at one year follow-up. Further clinical trial with larger sample size and longer follow up duration is warranted. The Translational Potential of this Article: This pilot RCT demonstrated the feasibility and potential effectiveness of BM-MSCs advanced therapy for patients with knee OA compared to HA injection. Further multi-center clinical trial with a larger sample size and longer follow up duration in accordance with latest regulatory guidelines is warranted to ascertain the long term safety and effectiveness of MSCs therapy for cartilage regeneration in OA. Registration: The study was registered in the Centre for Clinical Research Biostatistics - Clinical Trials Registry (CUHK_CCT00469).

Avulsion Fracture of Bicruciate Ligament and Patellar Tendon in Bicruciate-Retaining Total Knee Arthroplasty.

Tibial intercondylar fracture with anterior cruciate ligament avulsion is a unique but rare complication of bicruciate-retaining total knee arthroplasty. Here, we describe an even rarer condition that the tibial intercondylar fracture involved bicruciate ligament and partial patellar tendon avulsion fracture resulting in significant clinical instability in a 70-year-old woman, a combination not yet reported in the literature. Dual-energy computed tomography helped characterize the fracture. During revision surgery, the bicruciate retaining total knee arthroplasty was revised to posterior-stabilized total knee arthroplasty and the patellar tendon was repaired with a suture anchor. She recovered well progressively, and at 6 months, she could walk with the use of an assisted walking device.

Traditional Chinese-Hong Kong version of Forgotten Joint Score-12 (FJS-12) for patients with osteoarthritis of the knee underwent joint replacement surgery: cross-cultural and sub-cultural adaptation, and validation.

BACKGROUND: A patient-reported outcome (PRO) tool which reflects the outcomes of patients underwent total knee arthroplasty (TKA) are important to be "ceiling effect free" which commonly used PRO tools face. Forgotten joint score-12 (FJS-12) has been proved to reduce or even free from ceiling effect. FJS-12 has been translated to different languages. The objectives of this study are to validate FJS-12 in Traditional Chinese-Hong Kong language and look for the goodness of FJS-12 still exist in this language adapted FJS-12 version. METHODS: FJS-12 was administered to 75 patients whose majority was obese underwent TKA between September 2019 and March 2020. Patients completed 3 sets of questionnaires (FJS-12, Oxford Knee Score (OKS), and Numeric Rating Scale (NRS)) twice, 2 weeks apart. Reliability, internal consistency, responsiveness, test-retest agreement and discriminant validity were evaluated. RESULTS: Reliability of FJS-12 showed moderate to excellent internal consistency (Cronbach's α = 0.870). Test-retest reliability of FJS-12 was good (ICC = 0.769). Bland-Altman plot showed good test-retest agreement. Construct validity in terms of correlations between FJS-12 and OKS, and FJS-12 and NRS were moderate at baseline (Pearson's coefficient r = 0.598) and good at follow-up (r = 0.879). Smallest detectable change (Responsiveness) was higher than MIC. Floor effect was none observed, and ceiling effect was low. Discriminant validity was found to have no significance. BMI (obesity) did not affect FJS-12 outcomes. CONCLUSIONS: The Traditional Chinese-Hong Kong version of FJS-12 showed good test-retest reliability, validity, responsiveness, BMI non-specific, with no floor and low ceiling effects for patients who underwent TKA. Sub-culture differences in individual PRO tools should be considered in certain ethnicities and languages.

A community-centric multi-disciplinary education program with the 8-section brocade Tai Chi therapy for patients with osteoarthritis of the knee - a pilot study.

BACKGROUND: Osteoarthritis (OA) of the knee is one of the most common chronic degenerative joint diseases, and a multi-disciplinary approach to educating patients with OA knee are effective in symptoms management. Tai Chi exercise is a novel approach to relieving knee OA symptoms. Combining both educational program and Tai Chi has not yet been explored. METHODS: Multi-disciplinary education program included a total of 4-week 2-h weekly talks delivered by different health professionals with live demonstrations. This was then followed by a 1-h Tai Chi class (Baduanjin). Results from IPAQ (Physical activity level), WOMAC (evaluate knee OA conditions), and SF-36v2 (quality of life) were collected at the first class of education program, 3 and 6 months after the end of Tai Chi class. CSQ-8 (program effectiveness) was administered on the last day of Tai Chi class. RESULTS: One hundred and twelve patients joined the program. The overall attendance was over 90% with close-to-zero dropout rate. Satisfaction scored high in 85% of patients. WOMAC pain scores (p = 0.04) and SF-36v2 emotional role (p = 0.02) were statistically decreasing (improving) at 6 months after the program. SF-36v2 physical role and mental health tended to improve with time. CONCLUSIONS: Combining both multidisciplinary education program program and Tai Chi exercise for knee OA patients was proven feasible. This program received high satisfaction, high attendance and very low dropout rates without any adverse event. Patients' pain and emotion were significantly improved. A large-scale randomized trial introducing a control group is recommended. TRIAL REGISTRATION: Registry: ClinicalTrials.gov Registration number: NCT04204213 Date of registration: 18/12/2019 (Retrospectively registered).

The long-term results of total knee arthroplasty in octogenarian.

Aims: With increasing life expectancy and ageing population, more octogenarians would benefit from total knee arthroplasty (TKA). The aim of this study is to evaluate the survivorship of TKA in octogenarian and their long-term outcomes. Methods: This was a retrospective review of 67 patients aged above 80 years who had primary TKA performed between 2005 and 2013 at a single centre. A sex-matched younger cohort of 67 primary TKAs during the same time-period was recruited for control. Five and 10-year survival was calculated. Pre- and peri-operative factors were collected and compared. Post-operative range of motion, Knee Society Score (KSS) and Function Score (KFS) were collected and compared. Rate of revision, infection, aseptic loosening and mortality was collected. Results: The mean follow-up period was 10.39 ± 2.29 years. The 5- and 10-year survival of octogenarian group was 85.1% and 54.6%, respectively. Pre- and peri-operative factors between the octogenarian and control groups were comparable (p > 0.05). Both groups showed improvement in range of motion, KSS and KFS post-operatively. Rate of revision, aseptic loosening and deep infection was 0% in octogenarian and 1.5% in control group. Conclusion: TKA can be performed in patients with age above 80 years old with comparable post-op knee range, complication rate and long-term functional score. Advanced age should not be a limiting factor for TKA.

Comprehensive Analysis of Key Genes, Signaling Pathways and miRNAs in Human Knee Osteoarthritis: Based on Bioinformatics.

Background: Osteoarthritis (OA) is one of the main causes of disability in the elderly population, accompanied by a series of underlying pathologic changes, such as cartilage degradation, synovitis, subchondral bone sclerosis, and meniscus injury. The present study aimed to identify key genes, signaling pathways, and miRNAs in knee OA associated with the entire joint components, and to explain the potential mechanisms using computational analysis. Methods: The differentially expressed genes (DEGs) in cartilage, synovium, subchondral bone, and meniscus were identified using the Gene Expression Omnibus 2R (GEO2R) analysis based on dataset from GSE43923, GSE12021, GSE98918, and GSE51588, respectively and visualized in Volcano Plot. Venn diagram analyses were performed to identify the overlapping DEGs (overlapping DEGs) that expressed in at least two types of tissues mentioned above. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, protein-protein interaction (PPI) analysis, and module analysis were conducted. Furthermore, qRT-PCR was performed to validate above results using our clinical specimens. Results: As a result, a total of 236 overlapping DEGs were identified, of which 160 were upregulated and 76 were downregulated. Through enrichment analysis and constructing the PPI network and miRNA-mRNA network, knee OA-related key genes, such as HEY1, AHR, VEGFA, MYC, and CXCL12 were identified. Clinical validation by qRT-PCR experiments further supported above computational results. In addition, knee OA-related key miRNAs such as miR-101, miR-181a, miR-29, miR-9, and miR-221, and pathways such as Wnt signaling, HIF-1 signaling, PI3K-Akt signaling, and axon guidance pathways were also identified. Among above identified knee OA-related key genes, pathways and miRNAs, genes such as AHR, HEY1, MYC, GAP43, and PTN, pathways like axon guidance, and miRNAs such as miR-17, miR-21, miR-155, miR-185, and miR-1 are lack of research and worthy for future investigation. Conclusion: The present informatic study for the first time provides insight to the potential therapeutic targets of knee OA by comprehensively analyzing the overlapping genes differentially expressed in multiple joint components and their relevant signaling pathways and interactive miRNAs.

Osteonecrosis of the hip: is there a difference in the survivorship of total hip arthroplasty with or without previous vascular iliac bone grafting?

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a debilitating condition. Vascularized iliac bone graft (VIBG) is a joint-preserving surgery to improve blood supply to the avascular portion of the femoral head which may delay secondary osteoarthritis and total hip arthroplasty (THA). However, whether VIBG will affect the subsequent THA survivorship and outcomes are still uncertain. METHODS: Implant survivorship and clinical outcomes were compared between 27 patients who had undergone prior VIBG and 242 patients who had only undergone THA for ONFH. Baseline characteristics and the postoperative Harris Hip Score (HHS) were also recorded and compared between the two groups. Implant survivorship was determined using Kaplan-Meier survival analysis. RESULTS: The overall implant survival for all patients who had a primary diagnosis of ONFH and eventually underwent THA was 92.9%. There was no significant difference in the implant survivorship between the group who directly received THA (survivorship of 93%) and the group which failed VIBG and was subsequently converted to THA (survivorship of 91.9%) (p = 0.71). In addition, higher THA revision rates were associated with smokers and drinkers. CONCLUSIONS: VIBG may be a reasonable option as a "buy-time" procedure for ONFH. Even if conversion to THA is eventually required, patients may be reassured that the overall survivorship and clinical outcomes may not be compromised. Patients are recommended to give up smoking and binge drinking prior to THA to increase implant survival rate.

A randomized controlled trial on the effect of focal thermal therapy at acupressure points treating osteoarthritis of the knee.

BACKGROUND: Osteoarthritis of the knee is a common degenerative joint disorder in our ageing population. A combination of thermal therapy with a self-management exercise have shown a positive effect in the management of osteoarthritis of the knee. This study aimed to compare the effectiveness of topical heat pack versus focal application of heat therapy at the acupressure points in the treatment of osteoarthritis of the knee. METHODS: A randomized controlled trial was conducted in 76 patients with osteoarthritis of the knee, diagnosed by an experienced orthopedic surgeon. Following inclusion and exclusion selection, patients were randomly allocated to group 1 (Heat pack) or group 2 (Thermal gun). All patients received 30 min of treatment in each session, twice a week for 4 weeks. They also received an education program and taught home knee exercises. Outcome measurements were the visual analog scale (VAS) for pain intensity, muscle power, knee ROM, WOMAC and SF-12v2. RESULTS: In the Thermal gun group, function and total scores (WOMAC) and Physical Composite Scale (SF-12v2) were significantly improved after 8 sessions. Quadriceps strength was significantly improved after 8 weeks (from 4.42 to 4.63; p = 0.02). In the Heat pack group, flexion was significantly improved after 8 sessions (p = 0.02). Mean VAS scores after Heat pack treatment was consistently better (lower) than mean VAS scores after Thermal gun treatment. CONCLUSION: The combination of focal thermal therapy at acupressure points is a viable conservative treatment in osteoarthritis of the knee. The pressure at the acupressure points has a synergistic benefit than topical thermal therapy alone. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04735029 Date of registration: February 2, 2021 (Retrospectively registered).

Long-Term Outcome on the Mal-Seating of Ceramic-on-Ceramic Articulation in Total Hip Arthroplasty.

BACKGROUND: Total hip arthroplasty with ceramic-on-ceramic articulation aims to decrease wear, osteolysis, and aseptic loosening. A metal-backed ceramic liner was developed to reduce the risk of liner fracture. However, a significant number of cases of mal-seating of the metal-backed ceramic liner were observed in the 2000s, and there were concerns about their outcome. This review aims to investigate the long-term performance of the mal-seated ceramic liner. METHODS: From July 2003 to March 2007, 35 ceramic-on-ceramic total hip arthroplasties were performed with the Trident acetabular system. Clinical assessment, radiological analysis, and outcome assessment were performed. The prevalence of liner mal-seating and its long-term outcomes were investigated. RESULTS: There was liner mal-seating in 8 hips (22.9%). One liner was exchanged in the early postoperative period. No revision surgery was required for the remaining 7 hips at a mean follow-up of 14 years. All patients were free of hip pain with a mean Harris Hip Score of 94.7 at the most recent follow-up. No adverse event was observed. CONCLUSION: The long-term outcomes of the mal-seated liner were favorable. However, surgeons should exercise meticulous surgical technique to achieve a properly aligned liner within the acetabular shell to minimize this potentially correctable error.

End-stage knee osteoarthritis with and without sarcopenia and the effect of knee arthroplasty - a prospective cohort study.

BACKGROUND: Sarcopenia often accompanies osteoarthritis (OA), which is managed by total knee arthroplasty (TKA) in the late stage. Recent studies have suggested a higher risk of post-operative complications after TKA in sarcopenic OA subjects, but whether TKA can benefit them similar to non-sarcopenic subjects remains unexplored. This study aimed to examine the dynamic, mutual impact of sarcopenia and TKA in a one-year post-operative period. METHODS: This prospective cohort study was conducted between 2015 to 2018 at our hospital. Patients with end-stage OA of the knee waiting for TKA were recruited into the study. Primary outcome measures were change in muscle strength, mass and function. Secondary outcome measures were quality of life (QOL) measurements for pain, psychological and physical health. RESULTS: Fifty-eight patients were recruited, of which 79.3% were female and 32.8% already had sarcopenia at baseline. The average age of sarcopenic subjects and non-sarcopenic subjects was comparable (67.89 ± 7.07 vs. 67.92 ± 6.85; p = 0.99), but sarcopenic subjects had a lower body mass index (BMI) (25.64 ± 2.64 vs. 28.57 ± 4.04; p = 0.01). There was a statistically significant improvement in walking speed (10.24 ± 5.35 vs. 7.69 ± 2.68, p < 0.01) and muscle strength in both sarcopenic and non-sarcopenic patients after TKA. This was accompanied by an improvement trend in muscle mass in all subjects. There was no change in handgrip power before and after TKA and subsequent follow-up (19.31 ± 5.92 vs. 18.98 ± 6.37 vs. 19.36 ± 7.66; p = 0.97). QOL measured before, after and at follow-up with WOMAC (total: 42.27 ± 15.98 vs. 20.65 ± 15.24 vs. 16.65 ± 18.13) and SF12v2 (PCS: 33.06 ± 8.55 vs. 38.96 ± 8.01 vs. 40.67 ± 7.93) revealed progressive significant improvement (both comparisons p ≤ 0.01). Further analysis with the IPAQ also found increased engagement of high-intensity activities. CONCLUSIONS: This study showed that sarcopenia among patients with end-stage OA of the knee is not uncommon, but both sarcopenic and non-sarcopenic OA patients achieved significant clinical and functional improvement after TKA. Further studies with a larger sample size and different ethnicities could help ascertain a beneficial role of TKA in sarcopenic OA subjects. TRIAL REGISTRATION: Registry: ClinicalTrials.gov , Registration number: NCT03579329 . Date of registration: 6 July 2018. Retrospectively registered.

Prospective randomized trial comparing efficacy and safety of intravenous and intra-articular tranexamic acid in total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is associated with significant perioperative blood loss and postoperative allogenic blood transfusion. Tranexamic acid (TXA) reversibly blocks lysine binding sites on plasminogen molecules and inhibits plasmin formation. Comparisons of the efficacy and safety of intra-articular and intravenous TXA in primary TKA have not previously been reported. METHODS: A prospective randomized trial was conducted in 150 patients who underwent TKA, and these patients were randomized into three groups. Patients in Group A were injected by intra-articular TXA according to body weight (20 mg/kg). Patients in Group B received a standard dose of intra-articular TXA (2000 mg), and those in Group C were infused with TXA according to body weight (20 mg/kg) before tourniquet deflation and again 3 h later. Baseline characteristics and data collected at blood transfusion were compared. Differences among four time points (baseline, day 0, day 2, and day 5) were carried out using ANOVA. RESULTS: The hemoglobin levels at postoperative day 5 were 10.6 g/dL for Group A, 10.6 g/dL for Group B, and 10.7 g/dL for Group C. The drain output was 399 ml for Group A, 314 ml for Group B, and 305 ml for Group C (p = 0.03). Group C had significantly less drain output than Group A after post hoc comparisons (p = 0.05), whereas no significant difference was observed between Group A and B (p = 0.09) or between Group B and C. CONCLUSION: The weight-adjusted dose of TXA administered intravenously significantly reduced the drain output but not the total blood loss when compared with the weight-adjusted dose of TXA administered intra-articularly. No significant difference was observed in the other parameters among the three groups. TRIAL REGISTRATION: The Joint CUHK-NTEC CREC, CRE-2013.644-T . Registered 1 March 2014.

Impact of COVID-19 on orthopaedic clinical service, education and research in a university hospital.

The medical system of Hong Kong has been heavily affected by COVID-19. Adaptations are necessary to continue clinical care, education, and research, while minimising the risk of infection of our staff and students. Here, we report our early experience in response to the challenge posed by the COVID-19 pandemic. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This perspective can help to disseminate knowledge from an orthopaedic unit in a university hospital on overcoming the challenges of the COVID-19 pandemic, including clinical practice, education of medical students, and research.

Wnt16 attenuates osteoarthritis progression through a PCP/JNK-mTORC1-PTHrP cascade.

OBJECTIVES: Wnt16 is implicated in bone fracture and bone mass accrual both in animals and humans. However, its functional roles and molecular mechanism in chondrocyte differentiation and osteoarthritis (OA) pathophysiology remain largely undefined. In this study, we analysed its mechanistic association and functional relationship in OA progression in chondrocyte lineage. METHODS: The role of Wnt16 during skeletal development was examined by Col2a1-Wnt16 transgenic mice and Wnt16fl/fl;Col2a1-Cre (Wnt16-cKO) mice. OA progression was assessed by micro-CT analysis and Osteoarthritis Research Society International score after anterior cruciate ligament transection (ACLT) surgery with Wnt16 manipulation by adenovirus intra-articular injection. The molecular mechanism was investigated in vitro using 3D chondrocyte pellet culture and biochemical analyses. Histological analysis was performed in mouse joints and human cartilage specimens. RESULTS: Wnt16 overexpression in chondrocytes in mice significantly inhibited chondrocyte hypertrophy during skeletal development. Wnt16 deficiency exaggerated OA progression, whereas intra-articular injection of Ad-Wnt16 markedly attenuated ACLT-induced OA. Cellular and molecular analyses showed that, instead of ß-catenin and calcium pathways, Wnt16 activated the planar cell polarity (PCP) and JNK pathway by interacting mainly with AP2b1, and to a lesser extend Ror2 and CD146, and subsequently induced PTHrP expression through phosphor-Raptor mTORC1 pathway. CONCLUSIONS: Our findings indicate that Wnt16 activates PCP/JNK and crosstalks with mTORC1-PTHrP pathway to inhibit chondrocyte hypertrophy. Our preclinical study suggests that Wnt16 may be a potential therapeutic target for OA treatment.

Intra-articular injection of an antioxidant formulation did not improve structural degeneration in a rat model of post-traumatic osteoarthritis.

BACKGROUND/OBJECTIVE: Oxidative stress plays an important role in osteoarthritis (OA), causing inflammation and matrix degradation in joints. Previous studies have shown that antioxidants such as quercetin and vitamin C are potential candidates for treating OA. We aimed to determine whether a formulation of quercetin and vitamin C, together with an iron chelator, could retard OA progression in a post-traumatic OA rat model. METHODS: Twelve rats received anterior cruciate ligament transection for OA induction. At 20 weeks postoperation, weekly intra-articular injection of 50 µL of either saline or a formulation of quercetin dehydrate, sodium-L-ascorbate, and deferoxamine mesylate was given consecutively for 4 weeks (n = 5). Gait analysis was performed at pretreatment, and at 1 week and 5 weeks post-treatment. Microcomputed tomography scanning and histological scoring were performed at 5 weeks post-treatment. RESULTS: Gait analysis showed that intra-articular injections of antioxidant formulation did not improve pain-associated Limb Idleness Index over time (p = 0.449, Friedman test). However, at 5 weeks post-treatment, the treatment group exhibited a significantly lower Limb Idleness Index than the control group (p = 0.047, Mann-Whitney U test). At 5 weeks post-treatment, microcomputed tomography analysis revealed that there was no difference in any parameter between the treatment and control groups (p > 0.05, Student t test). Severe OA histopathological changes were found in both groups. The Osteoarthritis Research Society International scores of the treatment and control groups were 20 (range, 20-26) and 20 (range, 9-26), respectively (p = 0.382, Mann-Whitney U test). CONCLUSION: Intra-articular injection of an antioxidant formulation containing quercetin, vitamin C, and deferoxamine did not retard OA progression in advanced-stage OA. Future studies should aim to determine whether giving antioxidants in early OA, with prolonged drug retention, would be effective in retarding OA progression.