Total knee arthroplasty is safe for patients aged ≥80 years in Hong Kong.

INTRODUCTION: Total knee arthroplasty (TKA) is an efficacious operation that improves pain and function in patients with knee arthritis. Because of the population ageing trend in Hong Kong, there is a need to determine the safety profile of TKA in older patients. This study examined the age of patients who underwent TKA in the past 10 years in Hong Kong; the aim was to investigate the mortality safety profile and clinical outcomes of TKA in patients aged ≥80 years. METHODS: This study included all patients who underwent primary TKA in the Hospital Authority (HA) from 2010 to 2019. Incidences of 30-day, 90-day, and 1-year mortality were established. Clinical outcomes of patients aged ≥80 years in one cluster of HA hospitals were assessed. RESULTS: Between 2010 and 2019, 25 040 TKA procedures were conducted in all HA hospitals; 2491 were conducted in patients aged ≥80 years. The median age at operation was higher during 2015-2019 than during 2010-2014 (70 vs 69 years; P<0.001); furthermore, an increase was observed in the proportion of patients aged ≥80 years at the time of operation. Incidences of 30-day, 90-day, and 1-year mortality were 0.156%, 0.35%, and 1.09%, respectively. CONCLUSIONS: In this first study to examine the safety profile of TKA in older patients in Hong Kong, the mean age at the time of TKA and proportion of patients aged ≥80 years have steadily risen in the past decade. Even in older patients, TKA is a reasonably safe procedure.

Effects of enhanced recovery after surgery practices on postoperative recovery and length of stay after unilateral primary total hip or knee arthroplasty in a private hospital.

INTRODUCTION: Enhanced recovery after surgery (ERAS) practices improve postoperative recovery and reduce postoperative length of stay (LOS) in patients undergoing primary total hip arthroplasty (THA) or total knee arthroplasty (TKA). Our study investigated whether these promising results could be reproduced in a private hospital setting. METHODS: In total, 228 patients were included in the study cohort: the conventional group comprised 117 patients from 2012 to 2014, while the ERAS group comprised 111 patients from 2017 to 2018. All patients had undergone unilateral primary THA or TKA at a private hospital in Hong Kong. The outcome was postoperative LOS; factors affecting LOS were also investigated. RESULTS: No significant differences were found in any baseline parameters between the two groups of patients. The mean LOS was significantly shorter in the ERAS group than in the conventional group (3.28 ± 1.04 vs 5.16 ± 2.06 days, P<0.001). Moreover, a significantly greater proportion of patients could be discharged on or before postoperative day 3 in the ERAS group, compared with the conventional group (77.5% vs 13.7%, P<0.001). A significant difference in LOS was observed between general ward and private ward patients (3.06 ± 0.59 vs 3.66 ± 1.46 days, P=0.003). Sex, age, and nature of surgery (TKA vs THA) did not have significant effects on LOS. CONCLUSIONS: The ERAS practices yielded a significant improvement in postoperative LOS, compared to conventional practices, among patients who underwent unilateral primary THA or TKA in a private hospital.

Universal haemoglobin A1c screening reveals high prevalence of dysglycaemia in patients undergoing total knee arthroplasty.

INTRODUCTION: Diabetes mellitus is an established modifiable risk factor for periprosthetic joint infection (PJI). Haemoglobin A1c (HbA1c) is a glycaemic marker that correlates with diabetic complications and PJI. As diabetes and prediabetes are frequently asymptomatic, and there is increasing evidence to suggest a correlation between dysglycaemia and osteoarthritis, it is reasonable to provide HbA1c screening before total knee arthroplasty (TKA). The aim of the present study was to determine the prevalence of dysglycaemia in patients who underwent TKA and investigate whether HbA1c screening and optimisation of glycaemic control before TKA affects the incidence of PJI after TKA. METHODS: Patients who underwent primary TKA before and after routine HbA1c screening was introduced in our unit were reviewed. Prediabetes and diabetes were defined according to the American Diabetes Association. Patients with HbA1c ≥7.5% were referred to an endocrinologist for optimisation of glycaemic control before TKA. The incidence PJI, defined according to the Musculoskeletal Infection Society criteria, was recorded. RESULTS: A total of 729 patients (934 knees) had HbA1c screening before TKA. Of them, 17 (2.3%) and 184 (25.2%) patients had known prediabetes and diabetes, respectively, and 265 (36.4%) and 12 (1.6%) had undiagnosed prediabetes and diabetes, respectively. The incidence of PJI was significantly lower in all patients who received HbA1c screening compared with those who did not (0.2% vs 1.02%, P=0.027). CONCLUSION: Screening for HbA1c before TKA provides a cost-effective opportunity to identify undiagnosed dysglycaemia. Patients identified as having dysglycaemia receive modified treatment, significantly reducing the rate of PJI when compared with historical controls.

Blood transfusions in total knee arthroplasty: a retrospective analysis of a multimodal patient blood management programme.

PURPOSE: Transfusion is associated with increased perioperative morbidity and mortality in patients undergoing total knee arthroplasty (TKA). Patient blood management (PBM) is an evidence-based approach to maintain blood mass via haemoglobin maintenance, haemostasis optimisation, and blood loss minimisation. The aim of the present study was to assess the effectiveness of a multimodal PBM approach in our centre. METHODS: This was a single-centre retrospective study of patients who underwent primary TKA in Queen Mary Hospital in Hong Kong in 2013 or 2018, using data from the Clinical Data Analysis and Reporting System and a local joint registry database. Patient demographics, preoperative haemoglobin, length of stay, readmission, mean units of transfusion, postoperative prosthetic joint infection, and mortality data were compared between groups. RESULTS: In total, 262 and 215 patients underwent primary TKA in 2013 and 2018, respectively. The mean transfusion rate significantly decreased after PBM implementation (2013: 31.3%; 2018: 1.9%, P<0.001); length of stay after TKA also significantly decreased (2013: 14.49±8.10 days; 2018: 8.77±10.14 days, P<0.001). However, there were no statistically significant differences in readmission, early prosthetic joint infection, or 90-day mortality rates between the two groups. CONCLUSION: Our PBM programme effectively reduced the allogeneic blood transfusion rate in patients undergoing TKA in our institution. Thus, PBM should be considered in current TKA protocols to reduce rates of transfusions and related complications.

Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment.

OBJECTIVES: Wnt pathway upregulation contributes to knee osteoarthritis (OA) through osteoblast differentiation, increased catabolic enzymes, and inflammation. The small-molecule Wnt pathway inhibitor, lorecivivint (SM04690), which previously demonstrated chondrogenesis and cartilage protection in an animal OA model, was evaluated to elucidate its mechanism of action. DESIGN: Biochemical assays measured kinase activity. Western blots measured protein phosphorylation in human mesenchymal stem cells (hMSCs), chondrocytes, and synovial fibroblasts. siRNA knockdown effects in hMSCs and BEAS-2B cells on Wnt pathway, chondrogenic genes, and LPS-induced inflammatory cytokines was measured by qPCR. In vivo anti-inflammation, pain, and function were evaluated following single intra-articular (IA) lorecivivint or vehicle injection in the monosodium iodoacetate (MIA)-induced rat OA model. RESULTS: Lorecivivint inhibited intranuclear kinases CDC-like kinase 2 (CLK2) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Lorecivivint inhibited CLK2-mediated phosphorylation of serine/arginine-rich (SR) splicing factors and DYRK1A-mediated phosphorylation of SIRT1 and FOXO1. siRNA knockdowns identified a role for CLK2 and DYRK1A in Wnt pathway modulation without affecting ß-catenin with CLK2 inhibition inducing early chondrogenesis and DYRK1A inhibition enhancing mature chondrocyte function. NF-κB and STAT3 inhibition by lorecivivint reduced inflammation. DYRK1A knockdown was sufficient for anti-inflammatory effects, while combined DYRK1A/CLK2 knockdown enhanced this effect. In the MIA model, lorecivivint inhibited production of inflammatory cytokines and cartilage degradative enzymes, resulting in increased joint cartilage, decreased pain, and improved weight-bearing function. CONCLUSIONS: Lorecivivint inhibition of CLK2 and DYRK1A suggested a novel mechanism for Wnt pathway inhibition, enhancing chondrogenesis, chondrocyte function, and anti-inflammation. Lorecivivint shows potential to modify structure and improve symptoms of knee OA.

Non-surgical treatment of knee osteoarthritis.

Knee osteoarthritis is one of the most common degenerative diseases causing disability in elderly patients. Osteoarthritis is an increasing problem for ageing populations, such as that in Hong Kong. It is important for guidelines to be kept up to date with the best evidence-based osteoarthritis management practices available. The aim of this study was to review the current literature and international guidelines on non-surgical treatments for knee osteoarthritis and compared these with the current guidelines in Hong Kong, which were proposed in 2005. Internationally, exercise programmes for non-surgical management of osteoarthritis have been proven effective, and a pilot programme in Hong Kong for comprehensive non-surgical knee osteoarthritis management has been successful. Long-term studies on the effectiveness of such exercise programmes are required, to inform future changes to guidelines on osteoarthritis management.

Knocking out or pharmaceutical inhibition of fatty acid binding protein 4 (FABP4) alleviates osteoarthritis induced by high-fat diet in mice.

OBJECTIVES: Adipokines play roles in the pathogenesis of osteoarthritis (OA). Fatty acid binding protein 4 (FABP4) is a novel adipokine that is closely associated with obesity and metabolic diseases. The aim of this study was to discover the potential role of FABP4 in OA. METHODS: Seventy-two FABP4 knockout mice (KO) in C57BL/6N background and wild-type littermates (WT) (male, 6-week-old) were fed with a high-fat diet (HFD, 60% calorie) or standard diet (STD, 11.6% calorie) for 3 months, 6 months and 9 months (n = 6 each). In the parallel study, forty-eight 6-week-old male WT mice were fed with HFD or STD, and simultaneously treated with daily oral gavage of selective FABP4 inhibitor BMS309403 (15 mg/kg/d) or vehicle for 4 months and 6 months (n = 6 each). Serum FABP4 and cartilage oligomeric matrix protein (COMP) concentration was quantified. Histological assessment of knee OA and micro-CT analysis of subchondral bone were performed. RESULTS: HFD induced obesity in mice. After 3 months and 6 months of HFD, KO mice showed alleviated cartilage degradation and synovitis, with significantly lower COMP, modified Mankin OA score, and MMP-13/ADAMTS4 expression. After 6 months and 9 months of HFD, KO mice showed less osteophyte formation and subchondral bone sclerosis. Chronic treatment of BMS309403 for 4 months and 6 months significantly alleviated cartilage degradation, but had no effects on the subchondral bone. Knocking out or pharmaceutical inhibition of FABP4 did not have significant effects on lean mice fed with STD. CONCLUSIONS: Knocking out or pharmaceutical inhibition of FABP4 alleviates OA induced by HFD in mice.

A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee.

OBJECTIVES: Osteoarthritis (OA) is a degenerative disease characterized by loss of cartilage and increased subchondral bone within synovial joints. Wnt signaling affects the pathogenesis of OA as this pathway modulates both the differentiation of osteoblasts and chondrocytes, and production of catabolic proteases. A novel small-molecule Wnt pathway inhibitor, SM04690, was evaluated in a series of in vitro and in vivo animal studies to determine its effects on chondrogenesis, cartilage protection and synovial-lined joint pathology. DESIGN: A high-throughput screen was performed using a cell-based reporter assay for Wnt pathway activity to develop a small molecule designated SM04690. Its properties were evaluated in bone-marrow-derived human mesenchymal stem cells (hMSCs) to assess chondrocyte differentiation and effects on cartilage catabolism by immunocytochemistry and gene expression, and glycosaminoglycan breakdown. In vivo effects of SM04690 on Wnt signaling, cartilage regeneration and protection were measured using biochemical and histopathological techniques in a rodent acute cruciate ligament tear and partial medial meniscectomy (ACLT + pMMx) OA model. RESULTS: SM04690 induced hMSC differentiation into mature, functional chondrocytes and decreased cartilage catabolic marker levels compared to vehicle. A single SM04690 intra-articular (IA) injection was efficacious in a rodent OA model, with increased cartilage thickness, evidence for cartilage regeneration, and protection from cartilage catabolism observed, resulting in significantly improved Osteoarthritis Research Society International (OARSI) histology scores and biomarkers, compared to vehicle. CONCLUSIONS: SM04690 induced chondrogenesis and appeared to inhibit joint destruction in a rat OA model, and is a candidate for a potential disease modifying therapy for OA.

The emerging roles of functional imaging in ovarian cancer with peritoneal carcinomatosis.

This article reviews the emerging roles of functional imaging in the assessment of peritoneal carcinomatosis in ovarian cancer, focusing on the use of diffusion-weighted magnetic resonance imaging (DW-MRI) and 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography combined with computed tomography (PET-CT), their advantages and shortcomings as well as the added-value over conventional imaging.

Bacteriology and risk factors associated with periprosthetic joint infection after primary total knee arthroplasty: retrospective study of 2543 cases.

INTRODUCTION: Periprosthetic joint infection after total knee arthroplasty is a serious complication. This study aimed to identify risk factors and bacteriological features associated with periprosthetic joint infection after primary total knee arthroplasty performed at a teaching hospital. METHODS: We reviewed 2543 elective primary total knee arthroplasties performed at our institution from 1993 to 2013. Data were collected from the Hong Kong Hospital Authority's Clinical Data Analysis and Reporting System, the Infection Control Team, and the joint replacement division registry. The association between potential risk factors and periprosthetic joint infection was examined by univariable analysis and multivariable logistic regression. Univariable analyses were also performed to examine the association between potential risk factors and bacteriology and between potential risk factors, including bacteriology, and early-onset infection. RESULTS: The incidence of periprosthetic joint infection in our series was 1.34% (n=34). The incidence of early-onset infection was 0.39% (n=24). Of the periprosthetic joint infections, 29.4% were early-onset infections. In both univariable and multivariable analyses, only rheumatoid arthritis was a significant predictor of periprosthetic joint infection. Methicillin-sensitive Staphylococcus aureus was the most common causative organism. We did not identify any significant association between potential risk factors and bacteriology. Periprosthetic joint infection caused by skin flora was positively associated with early-onset infection but the association was not statistically significant. CONCLUSION: The incidence of periprosthetic joint infection after elective primary total knee arthroplasty performed at our institution from 1993 to 2013 was 1.34%. Rheumatoid arthritis was a significant risk factor for periprosthetic joint infection.

Ultrasound-guided synovial Tru-cut biopsy: indications, technique, and outcome in 111 cases.

OBJECTIVE: To investigate the diagnostic performance of ultrasound-guided synovial biopsy. METHODS: Clinical notes, pathology and microbiology reports, ultrasound and other imaging studies of 100 patients who underwent 111 ultrasound-guided synovial biopsies were reviewed. Biopsies were compared with the final clinical diagnosis established after synovectomy (n = 43) or clinical/imaging follow-up (n = 57) (mean 30 months). RESULTS: Other than a single vasovagal episode, no complication of synovial biopsy was encountered. One hundred and seven (96 %) of the 111 biopsies yielded synovium histologically. Pathology ± microbiology findings for these 107 conclusive biopsies comprised synovial tumour (n = 30, 28 %), synovial infection (n = 18, 17 %), synovial inflammation (n = 45, 42 %), including gouty arthritis (n = 3), and no abnormality (n = 14, 13 %). The accuracy, sensitivity, and specificity of synovial biopsy was 99 %, 97 %, and 100 % for synovial tumour; 100 %, 100 %, and 100 % for native joint infection; and 78 %, 45 %, and 100 % for prosthetic joint infection. False-negative synovial biopsy did not seem to be related to antibiotic therapy. CONCLUSION: Ultrasound-guided Tru-cut synovial biopsy is a safe and reliable technique with a high diagnostic yield for diagnosing synovial tumour and also, most likely, for joint infection. Regarding joint infection, synovial biopsy of native joints seems to have a higher diagnostic yield than that for infected prosthetic joints. KEY POINTS: • Ultrasound-guided Tru-cut synovial biopsy has high accuracy (99 %) for diagnosing synovial tumour. • It has good accuracy, sensitivity, and high specificity for diagnosis of joint infection. • Synovial biopsy of native joints works better than biopsy of prosthetic joints. • A negative synovial biopsy culture from a native joint largely excludes septic arthritis. • Ultrasound-guided Tru-cut synovial biopsy is a safe and well-tolerated procedure.

Why do Hong Kong patients need total hip arthroplasty? An analysis of 512 hips from 1998 to 2010.

INTRODUCTION: The number of patients undergoing total hip replacement surgeries has increased as a result of a rise in the ageing population. This study reviewed the demographics and disease spectrum leading to primary total hip replacement in the Chinese population from 1998 to 2010. METHODS: This case series was conducted in a university teaching hospital in Hong Kong. Data from the prospective joint registry of all patients who underwent primary total hip replacement from January 1998 to December 2010 were reviewed. Patients' age and sex, diagnosis, as well as the Harris Hip Scores before operation and at the last follow-up were described. RESULTS: There were 512 primary total hip replacements performed on 419 patients (43.4% males) during the study period. All had clinical follow-up for at least 2 years. The mean age of the patients was 57.6 (standard deviation, 16.6) years. In males, the main aetiology was osteonecrosis (50.9%), ankylosing spondylitis (19.5%), and post-traumatic arthritis (8.5%). For females, it was osteonecrosis (33.0%), primary osteoarthritis (18.8%), and post-traumatic arthritis (15.8%). Alcohol-induced (52.5%) and idiopathic (40.7%) was the most common cause of osteonecrosis in males and females, respectively. The mean preoperative Harris Hip Score and that at last follow-up was 43.9 (standard deviation, 18.3) and 89.7 (standard deviation, 13.0), respectively. CONCLUSIONS: Osteonecrosis was the most common aetiology leading to total hip replacement although there were different causes in both sexes leading to it. The clinical result in terms of Harris Hip Score was good for all patients who required total hip replacement.

A review of the clinical approach to persistent pain following total hip replacement.

Total hip arthroplasty is effective in reducing pain and improving functional outcome for a variety of hip pathologies. Approximately 27% patients, however, complain of pain at 6 months' follow-up following surgery. The pain may worsen over time and can become severe and chronic in around 4% of patients who ultimately require revision surgery. Therefore, it is important for clinicians to comprehensively assess patients undergoing total hip arthroplasty in order to identify the underlying pathology of a painful hip and then offer prompt treatment. Causes of hip pain after total hip arthroplasty are analysed in this article, as well as the systematic approach to evaluation and appropriate diagnostic investigations.

An Unusual Hydrops Fetalis Associated with Compound Heterozygosity for Krüppel-like Factor 1 mutations.

Hydrops fetalis is commonly due to Hb Bart's (γ4) disease in South East Asia. Here, we report an unusual case of hydrops fetalis due to congenital dyserythropoietic anemia (CDA) associated with compound heterozygosity for Krüppel-like factor 1 (KLF1) gene mutations. Fetal cardiomegaly was first detected on routine mid-trimester scan in a pregnant woman with normal mean corpuscular volume (MCV) and Rhesus positive status. The fetus subsequently developed hydrops fetalis, and cordocentesis showed severe fetal anemia with a hemoglobin (Hb) level of 3.4 g/dL. Common causes of fetal anemia including Hb Bart's disease, parvovirus infection, and red cell antibodies were excluded. In view of the marked increase in erythroblasts at various stages of erythropoiesis, the diagnosis of CDA was suspected. We screened the couple for previously reported KLF1 gene mutations, showing that the mother was heterozygous for the c.525_526insCGGCGCC, p.Gly176Argfs*179 mutation, and her husband heterozygous for c.1012C>A, p.Pro338Thr mutation. The fetus was a compound heterozygote for these two KLF1 mutations. After counseling, repeated intrauterine transfusions were given at 27, 29, and 34 weeks' gestation; the hydrops fetalis was resolved. The baby was delivered at 34 weeks' gestation and required monthly blood transfusions but was otherwise thriving. Bone marrow aspiration at 10 months of age showed the features of ineffective erythropoiesis, compatible with CDA. In conclusion, hydrops fetalis can rarely be due to CDA associated with a compound heterozygous mutation for KLF1 gene mutations, and be managed by repeated intrauterine transfusions. Our present report adds to the wide clinical spectrum of KLF1 mutations.

The cardiopulmonary effects and quality of anesthesia after induction with alfaxalone in 2-hydroxypropyl-ß-cyclodextrin in dogs and cats: a systematic review.

To systematically review the quality of evidence comparing the cardiopulmonary effects and quality of anesthesia after induction with alfaxalone vs. other anesthetic agents in dogs and cats. Studies published from 2001 until 20th May 2013 were identified with the terms 'alfaxan' OR 'alfaxalone' OR 'alphaxalone' in electronic databases: Discovery, PubMed, ScienceDirect, and Wiley Interscience. The study design and risk of bias of all included studies were assessed. Twenty-two studies from 408 (22 of 408, 5.39%) satisfied the inclusion criteria. Fourteen studies (14 of 22, 64%) focused on dogs and nine (9 of 22, 40%) on cats. One study had both dogs and cats as subjects. (Hunt et al., 2013) Twelve studies were rated an LOE1, and six of these as ROB1. One, seven, and two studies were rated as LOE2, LOE3, and LOE5, respectively. In dogs, strong evidence shows that induction quality with either alfaxalone-HPCD or propofol is smooth. Moderate evidence supports this finding in cats. In dogs, moderate evidence shows that there is no significant change in heart rate after induction with either alfaxalone-HPCD or propofol. In cats, moderate evidence shows no significant difference in postinduction respiratory rate and heart rate between alfaxalone-HPCD and propofol induction. Strong evidence shows dogs and cats have smooth recoveries after induction using either alfaxalone-HPCD or propofol, before reaching sternal recumbency.

The emerging role of endothelin-1 in the pathogenesis of subchondral bone disturbance and osteoarthritis.

Mounting evidence suggests reconceptualizing osteoarthritis (OA) as an inflammatory disorder. Trauma and obesity, the common risk factors of OA, could trigger the local or systemic inflammatory cytokines cascade. Inflammatory bone loss has been well documented; yet it remains largely unknown about the link between the inflammation and hypertrophic changes of subchondral bone seen in OA, such as osteophytosis and sclerosis. Amid a cohort of inflammatory cytokines, endothelin-1 (ET-1) could stimulate the osteoblast-mediated bone formation in both physiological (postnatal growth of trabecular bone) and pathological conditions (bone metastasis of prostate or breast cancer). Also, ET-1 is known as a mitogen and contributes to fibrosis in various organs, e.g., skin, liver, lung, kidney heart and etc., as a result of inflammatory or metabolic disorders. Subchondral bone sclerosis shared the similarity with fibrosis in terms of the overproduction of collagen type I. We postulated that ET-1 might have a hand in the subchondral bone sclerosis of OA. Meanwhile, ET-1 was also able to stimulate the production of matrix metalloproteinase (MMP)-1 and 13 by articular chondrocytes and synoviocytes, by which it might trigger the enzymatic degradation of articular cartilage. Taken together, ET-1 signaling may play a role in destruction of bone-cartilage unit in the pathogenesis of OA; it warrants further investigations to potentiate ET-1 as a novel diagnostic biomarker and therapeutic target for rescue of OA.