Publications by authors named "Guanghua Lei"

88 Publications

Identifying predictors of response to oral non-steroidal anti-inflammatory drugs and paracetamol in osteoarthritis: a hypothesis-driven protocol for an OA Trial Bank individual participant data meta-analysis.

BMJ Open 2021 08 11;11(8):e048652. Epub 2021 Aug 11.

Academic Rheumatology, Clinical Sciences Building, University of Nottingham, City Hospital, Nottingham, UK.

Introduction: Symptomatic treatments for osteoarthritis (OA) provide only small-to-moderate efficacy over placebo in randomised controlled trials (RCTs). Treatment guidelines therefore have emphasised the need to identify predictors of treatment response through subgroup and multiple regression analysis. Individual participant data (IPD) meta-analysis is recommended as an efficient approach for this purpose. To our knowledge, this has not been undertaken for oral non-steroidal anti-inflammatory drugs (NSAIDs), including paracetamol, in OA. In this IPD meta-analysis, we aim to identify RCTs with specific mechanistic features related to OA pain, such as joint inflammation. We hypothesise that NSAIDs may work better for participants with joint inflammation, whereas paracetamol may not.

Methods And Analysis: A comprehensive literature search will be conducted on the databases of Web of Science, Embase, Medline, CINAHL, AMED and the Cochrane Library from 1 January 1998 to 1 December 2020. All RCTs related to oral NSAIDs or paracetamol including placebo-controlled trials in people with OA that have evaluated pain-related peripheral risk factors (eg, clinically detected knee effusion, synovial hypertrophy or effusion on imaging, knee morning stiffness, elevated serum C-reactive protein (CRP) level) and/or central pain risk factors (eg, pain elsewhere, depression, anxiety, sleep disturbance) will be retrieved. The outcome will be change in pain from baseline. Change in function and patient global assessment will also be included as outcomes if available. Investigators of all eligible trials will be contacted for IPD. Multilevel regression models will be used to identify predictors for the specific (active-placebo) and the overall treatment effect (change from baseline in active group).

Ethics And Dissemination: No identifiable data will be included in this study and no formal ethics approval is required as no new data collection will be processed. Results of this hypothesis-driven IPD meta-analysis will be disseminated through conference presentations and publication in peer-reviewed journals.

Prospero Registration Number: CRD42020165098.
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http://dx.doi.org/10.1136/bmjopen-2021-048652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359469PMC
August 2021

Efficacy and safety of tramadol for knee or hip osteoarthritis: a systematic review and network meta-analysis of randomized controlled trials.

Arthritis Care Res (Hoboken) 2021 Jul 12. Epub 2021 Jul 12.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Objective: To examine efficacy and safety of tramadol for knee or hip osteoarthritis (OA).

Methods: Pubmed, Embase, Cochrane Library and Web of Science were searched up to May 2020 for randomized controlled trials (RCTs) comparing any of the following interventions: tramadol 100 mg/day, 200 mg/day and 300 mg/day, and placebo for knee or hip OA. Pain and function were measured at or nearest to twelve weeks for efficacy. Gastrointestinal, cardiovascular and central nervous system (CNS) adverse effects (AEs), and withdrawals were measured for safety. Bayesian network meta-analysis was conducted.

Results: Six RCTs (3,611 participants) were included. Tramadol 100 mg/day (standardized mean difference [SMD]=-0.16, 95% confidence interval [CI]: -0.34 to 0.00), 200 mg/day (SMD=-0.21, 95%CI: -0.37 to -0.06) and 300 mg/day (SMD=-0.30, 95%CI: -0.48 to -0.14) were statistically more effective than placebo in pain relief, but only tramadol 300 mg/day was better than placebo in functional improvement (SMD=-0.24, 95%CI: -0.47 to -0.03). Tramadol 100 mg/day (relative risk [RR]=2.29, 95% credible interval [CrI]: 1.22 to 4.25), 200 mg/day (RR=4.35, 95%CrI: 2.31 to 8.01) and 300 mg/day (RR=6.02, 95%CrI: 3.22 to 11.1) involved a higher risk of gastrointestinal AEs. Similarly, tramadol 100-300 mg/day showed a higher risk of CNS AEs and withdrawals. However, the risk of cardiovascular AEs remained unclear.

Conclusions: Only tramadol 300mg/day showed minimal improvement in pain and function but with increasing AEs compared with placebo. Tramadol may not be sufficiently recommended for knee or hip OA by presented evidence, especially in patients with the risk of gastrointestinal and CNS AEs.
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http://dx.doi.org/10.1002/acr.24750DOI Listing
July 2021

Engineering osteoarthritic cartilage model through differentiating senescent human mesenchymal stem cells for testing disease-modifying drugs.

Sci China Life Sci 2021 Jun 4. Epub 2021 Jun 4.

Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.

Significant cellular senescence has been observed in cartilage harvested from patients with osteoarthritis (OA). In this study, we aim to develop a senescence-relevant OA-like cartilage model for developing disease-modifying OA drugs (DMOADs). Specifically, human bone marrow-derived mesenchymal stromal cells (MSCs) were expanded in vitro up to passage 10 (P10-MSCs). Following their senescent phenotype formation, P10-MSCs were subjected to pellet culture in chondrogenic medium. Results from qRT-PCR, histology, and immunostaining indicated that cartilage generated from P10-MSCs displayed both senescent and OA-like phenotypes without using other OA-inducing agents, when compared to that from normal passage 4 (P4)-MSCs. Interestingly, the same gene expression differences observed between P4-MSCs and P10-MSC-derived cartilage tissues were also observed between the preserved and damaged OA cartilage regions taken from human samples, as demonstrated by RNA Sequencing data and other analysis methods. Lastly, the utility of this senescence-initiated OA-like cartilage model in drug development was assessed by testing several potential DMOADs and senolytics. The results suggest that pre-existing cellular senescence can induce the generation of OA-like changes in cartilage. The P4- and P10-MSCs derived cartilage models also represent a novel platform for predicting the efficacy and toxicity of potential DMOADs on both preserved and damaged cartilage in humans.
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http://dx.doi.org/10.1007/s11427-021-1933-7DOI Listing
June 2021

Prevalence of ultrasound-detected knee synovial abnormalities in a middle-aged and older general population-the Xiangya Osteoarthritis Study.

Arthritis Res Ther 2021 06 2;23(1):156. Epub 2021 Jun 2.

Department of Orthopaedics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.

Background: There is paucity of data on the prevalence of ultrasound-detected synovial abnormalities in the general population, and the relationship between synovial changes and knee pain remains unclear. We examined the prevalence of synovial abnormalities on ultrasound and the relationship of these features with knee pain and radiographic osteoarthritis (ROA) in a community sample.

Methods: Participants aged 50 years or over were from the Xiangya Osteoarthritis Study, a community-based cohort study. Participants were questioned about chronic knee pain and underwent (1) ultrasonography of both knees to determine presence of synovial hypertrophy (≥ 4 mm), effusion (≥ 4 mm), and Power Doppler signal [PDS; yes/no]; and (2) standard radiographs of both knees (tibiofemoral and patellofemoral views) to determine ROA.

Results: There were 3755 participants (mean age 64.4 years; women 57.4%). The prevalence of synovial hypertrophy, effusion, and PDS were 18.1% (men 20.2%; women 16.5%), 46.6% (men 49.9%; women 44.2%), and 4.9% (men 4.9%; women 5.0%), respectively, and increased with age (P for trend < 0.05). Synovial abnormalities were associated with knee pain, with adjusted odds ratios (aORs) of 2.39 (95% confidence interval [CI] 2.00-2.86) for synovial hypertrophy, 1.58 (95%CI 1.39-1.80) for effusion, and 4.36 (95%CI 3.09-6.17) for PDS. Similar associations with ROA were observed, the corresponding aORs being 4.03 (95%CI 3.38-4.82), 2.01 (95%CI 1.76-2.29), and 6.49 (95%CI 4.51-9.35), respectively. The associations between synovial hypertrophy and effusion with knee pain were more pronounced among knees with ROA than those without ROA, and the corresponding P for interaction were 0.004 and 0.067, respectively.

Conclusions: Knee synovial hypertrophy and effusion are more common and increase with age, affecting men more than women. All three ultrasound-detected synovial abnormalities associate both with knee pain and ROA, and knee synovial hypertrophy or effusion and ROA may interact to increase the risk of knee pain.
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http://dx.doi.org/10.1186/s13075-021-02539-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170794PMC
June 2021

Reply to Non-coding RNAs, osteoarthritis and the microbiome: new therapeutic targets?

Arthritis Rheumatol 2021 May 13. Epub 2021 May 13.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.

We appreciate the interest of Sirufo et al. in our manuscript describing the association between gut microbiota and symptomatic hand osteoarthritis (SHOA) (1). Hand osteoarthritis (OA) is a common joint disorder. Individuals with hand OA often reported pain symptom and functional limitation, including difficulty in undertaking daily activities. To date, few risk factors have been identified for hand OA and there is no effective treatment that can halt the disease progression. The common management of hand OA is to control pain and improve function.
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http://dx.doi.org/10.1002/art.41797DOI Listing
May 2021

Targeted apoptosis of macrophages and osteoclasts in arthritic joints is effective against advanced inflammatory arthritis.

Nat Commun 2021 04 12;12(1):2174. Epub 2021 Apr 12.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610064, China.

Insufficient apoptosis of inflammatory macrophages and osteoclasts (OCs) in rheumatoid arthritis (RA) joints contributes toward the persistent progression of joint inflammation and destruction. Here, we deliver celastrol (CEL) to selectively induce apoptosis of OCs and macrophages in arthritic joints, with enzyme-responsive nanoparticles (termed PRNPs) composed of RGD modified nanoparticles (termed RNPs) covered with cleavable PEG chains. CEL-loaded PRNPs (CEL-PRNPs) dually target OCs and inflammatory macrophages derived from patients with RA via an RGD-αvβ3 integrin interaction after PEG cleavage by matrix metalloprotease 9, leading to increased apoptosis of these cells. In an adjuvant-induced arthritis rat model, PRNPs have an arthritic joint-specific distribution and CEL-PRNPs efficiently reduce the number of OCs and inflammatory macrophages within these joints. Additionally, rats with advanced arthritis go into inflammatory remission with bone erosion repair and negligible side effects after CEL-PRNPs treatment. These findings indicate potential for targeting chemotherapy-induced apoptosis in the treatment of advanced inflammatory arthritis.
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http://dx.doi.org/10.1038/s41467-021-22454-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042091PMC
April 2021

Association Between Gut Microbiota and Symptomatic Hand Osteoarthritis: Data From the Xiangya Osteoarthritis Study.

Arthritis Rheumatol 2021 09 6;73(9):1656-1662. Epub 2021 Aug 6.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, and Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China.

Objective: Systemic inflammatory factors have been implicated in symptomatic hand osteoarthritis (OA). Gut microbiome dysbiosis promotes systemic inflammation. The aim of this study was to examine the association between the gut microbiome and the presence of symptomatic hand OA in a population-based study.

Methods: Study participants were subjects of the Xiangya Osteoarthritis Study, a community-based observational study conducted in the Hunan Province of China. Symptomatic hand OA was defined as the presence of both symptoms and radiographic OA in the same hand. The gut microbiome was analyzed using 16S ribosomal RNA gene sequencing in stool samples. We examined the relation of α-diversity, β-diversity, relative abundance of taxa, and potential bacterial functional pathways to symptomatic hand OA.

Results: A total of 1,388 participants (mean age 61.3 years, 57.4% women) were included in the study, of whom 72 had symptomatic hand OA (prevalence of symptomatic hand OA 5.2%). Beta-diversity of the gut microbiome, but not α-diversity, was significantly associated with the presence of symptomatic hand OA (P = 0.003). Higher relative abundance of the genera Bilophila and Desulfovibrio as well as lower relative abundance of the genus Roseburia was associated with symptomatic hand OA. Most functional pathways (i.e., those annotated in the KEGG Ortholog hierarchy) that were observed to be altered in participants with symptomatic hand OA belonged to the amino acid, carbohydrate, and lipid metabolic pathways.

Conclusion: This large, population-based study provides the first evidence that alterations in the composition of the gut microbiome were observed among study participants who had symptomatic hand OA, and a low relative abundance of Roseburia but high relative abundance of Bilophila and Desulfovibrio at the genus level were associated with prevalent symptomatic hand OA. These findings may help investigators understand the role of the microbiome in the development of symptomatic hand OA and could contribute to potential translational opportunities.
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http://dx.doi.org/10.1002/art.41729DOI Listing
September 2021

Macrophage migration inhibitory factor may play a protective role in osteoarthritis.

Arthritis Res Ther 2021 02 20;23(1):59. Epub 2021 Feb 20.

Division of Biomedical Sciences (Genetics), Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada.

Background: Osteoarthritis (OA) is the most prevalent form of arthritis and the major cause of disability and overall diminution of quality of life in the elderly population. Currently there is no cure for OA, partly due to the large gaps in our understanding of its underlying molecular and cellular mechanisms. Macrophage migration inhibitory factor (MIF) is a procytokine that mediates pleiotropic inflammatory effects in inflammatory diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, data on the role of MIF in OA is limited with conflicting results. We undertook this study to investigate the role of MIF in OA by examining MIF genotype, mRNA expression, and protein levels in the Newfoundland Osteoarthritis Study.

Methods: One hundred nineteen end-stage knee/hip OA patients, 16 RA patients, and 113 healthy controls were included in the study. Two polymorphisms in the MIF gene, rs755622, and -794 CATT, were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR followed by automated capillary electrophoresis, respectively. MIF mRNA levels in articular cartilage and subchondral bone were measured by quantitative polymerase chain reaction. Plasma concentrations of MIF, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) were measured by enzyme-linked immunosorbent assay.

Results: rs755622 and -794 CATT genotypes were not associated with MIF mRNA or protein levels or OA (all p ≥ 0.19). MIF mRNA level in cartilage was lower in OA patients than in controls (p = 0.028) and RA patients (p = 0.004), while the levels in bone were comparable between OA patients and controls (p = 0.165). MIF protein level in plasma was lower in OA patients than in controls (p = 3.01 × 10), while the levels of TNF-α, IL-6 and IL-1β in plasma were all significantly higher in OA patients than in controls (all p ≤ 0.0007). Multivariable logistic regression showed lower MIF and higher IL-1β protein levels in plasma were independently associated with OA (OR per SD increase = 0.10 and 8.08; 95% CI = 0.04-0.19 and 4.42-16.82, respectively), but TNF-α and IL-6 became non-significant.

Conclusions: Reduced MIF mRNA and protein expression in OA patients suggested MIF might have a protective role in OA and could serve as a biomarker to differentiate OA from other joint disorders.
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http://dx.doi.org/10.1186/s13075-021-02442-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896408PMC
February 2021

MgO Nanoparticles Protect against Titanium Particle-Induced Osteolysis in a Mouse Model Because of Their Positive Immunomodulatory Effect.

ACS Biomater Sci Eng 2020 05 17;6(5):3005-3014. Epub 2020 Apr 17.

School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore.

Aseptic prosthetic loosening (APL) often leads to the failure of prostheses. It is inseparable from wear-particle-induced macrophage-mediated inflammatory responses and osteolysis. Mg is a metal ion with excellent anti-inflammatory properties. Herein, Mg was introduced into a nanomedicine (MgO nanoparticles (MNPs)) to protect against APL. MNPs could be phagocytized by macrophages and gradually degraded intracellularly. Following MNPs treatment, lipopolysaccharide (LPS)-activated macrophages polarized into deeper M1 phenotype at 6 h but then switched to the M2 phenotype at 48 h. Furthermore, the MNPs suppressed the titanium (Ti) particle-induced osteoclastogenesis and osteolysis in vivo. However, the MNPs exhibited no impact on the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and even inhibited osteogenesis in vitro. The contrary results between the in vitro and in vivo experiments imply that macrophages are the key factor in the inhibited osteoclastogenesis in vivo because the pathogenic process of APL is mainly attributed to macrophages, osteoblasts, and osteoclasts. Accordingly, an indirect coculture system was designed that considers the immunomodulatory effect of macrophages. RANKL-induced osteoclastogenesis was significantly inhibited under the influence of MNPs in the indirect coculture system. Taken together, the MNPs inhibited the inflammatory responses of macrophages provoked by the Ti particles and thus regulated the expressions of RANKL and OPG in osteoblasts to suppress osteoclastogenesis. The target cell of MNPs was macrophages but not osteoclasts, indicating the importance of the immunomodulatory effect of macrophages. These results collectively demonstrated that MNPs can prevent APL and other osteolysis-related diseases.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01852DOI Listing
May 2020

Response to: 'Correspondence on 'Risk of venous thromboembolism in knee, hip and hand osteoarthritis: a general population-based cohort study'' by Lin .

Ann Rheum Dis 2021 Jan 6. Epub 2021 Jan 6.

Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

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http://dx.doi.org/10.1136/annrheumdis-2020-219747DOI Listing
January 2021

Using MgO nanoparticles as a potential platform to precisely load and steadily release Ag ions for enhanced osteogenesis and bacterial killing.

Mater Sci Eng C Mater Biol Appl 2021 Feb 22;119:111399. Epub 2020 Aug 22.

State Key Laboratory of Powder Metallurgy, Central South University, Changsha 410083, PR China. Electronic address:

Bio-functional fillers including bio-ceramic, degradable metallic and composite particles are commonly introduced into bone tissue engineering (BTE) scaffolds to endow the materials with specific biological functions for enhanced bone defect therapy. In this work, MgO nanoparticles (NPs) were employed as a potential platform for precise loading and sustained release of Ag. The results showed that MgO NPs possessed strong adsorption capacity (almost 100%) towards Ag in AgNO solutions with different concentrations (0.1, 1 and 10 mM). After the adsorption of Ag in AgNO solutions, cube-shaped MgO NPs transformed to lamella-structured nano-composites (NCs) composed of Mg(OH) and AgO, which were referred as MgO-xAg (x = 0.1, 1 or 10) NCs depending on the employed concentration of AgNO solution. After being suspended in distilled water, as-prepared positively charged NCs underwent a fast degradation process during the initial 4 days. From day 4 and 14, steady release behaviors of Mg and/or Ag from the NCs were noticed. With the lowest loading amount of Ag, MgO-0.1Ag NCs did not exhibit significant modulatory effect on SaOS-2 cell response. On the contrary, MgO-10Ag NCs loaded with the highest amount of Ag showed significant cyto-toxicity towards SaOS-2 cells. With appropriate amount of Ag loading, MgO-1Ag NCs showed significantly stimulatory effects on SaOS-2 cell proliferation and differentiation. This is evidenced by the enhanced cell viability, alkaline phosphatase (ALP) activity and collagen (COL) production as well as the gene expressions of ALP, COL and osteoprotegerin (OPG) in MgO-1Ag group. Moreover, MgO-1Ag exhibited strong bactericidal capacity against both Escherichia coli and Staphylococcus aureus. Together, the results indicate that MgO could be employed as a potential platform for precise loading and sustained release of Ag. MgO-1Ag NCs are promising to be used as bio-functional fillers in BTE scaffolds for simultaneously promoted osteogenesis and bacterial killing.
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http://dx.doi.org/10.1016/j.msec.2020.111399DOI Listing
February 2021

Developing a toolbox for identifying when to engage senior surgeons in emergency general surgery: A multicenter cohort study.

Int J Surg 2021 Jan 2;85:30-39. Epub 2020 Dec 2.

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China. Electronic address:

Background: Having a senior surgeon present for high-risk patients is an important safety measure in emergency surgery, but 24-h consultant cover is not efficient. We aimed to develop a user-friendly toolbox (risk identification, outcome prediction and patient stratification) to support when to involve a senior surgeon.

Materials And Methods: We included 11,901 general surgery patients (10.0% emergencies) in a multicenter prospective cohort in China (2015-2016). Patient information and surgeons' seniority were compared between emergency and elective surgery with the same procedure codes. Risk indicators common in these two surgical timings and specific to emergency surgery were identified, and their clinical importance was evaluated by a working group of 48 experienced surgeons. Predictive models for mortality and morbidity were built using logistic regression models. Stratification rules were created to balance patients' risk and surgeons' caseload with an Acute Call Team (ACT) model.

Results: Emergency patients had significantly higher risks of mortality (3.6% vs 0.6%) and morbidity (7.8% vs 4.3%) than elective patients, but disproportionally fewer senior surgeons (59.9% vs 91.4%) were present. Using three risk indicators (American Society of Anesthesiologists score, age, blood urea nitrogen), C-statistic (95% CI) for prediction of emergency mortality was high [0.90 (0.84-0.96)]. It was less complex but equally accurate as two existing and validated models (0.86 [0.79-0.93] and 0.86 [0.77-0.95]). Using five indicators, C-statistic (95% CI) was moderate for prediction of overall morbidity [0.77 (0.72-0.83)], but high for severe morbidity [0.92 (0.88-0.97)]. Based on stratification rules of the ACT model, patient mortality and morbidity were 0.5% and 5.3% in the low-risk stratum (composing 64.6% of emergency caseload), and 15.9% and 29.0% in the very high-risk stratum (6.9% of caseload).

Conclusion: These findings show the practical feasibility of using a risk assessment tool to direct senior surgeons' involvement in emergency general surgery.
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http://dx.doi.org/10.1016/j.ijsu.2020.11.004DOI Listing
January 2021

Guidelines for the diagnosis and treatment of osteoarthritis in China (2019 edition).

Ann Transl Med 2020 Oct;8(19):1213

Academic Rheumatology, Clinical Sciences Building, University of Nottingham, City Hospital, Nottingham, UK.

Osteoarthritis (OA) is a degenerative disease of middle-aged and elderly people, contributed a higher burden of disease in China and the world. In 2017, under the support of the Rheumatology and Immunology Expert Committee of the Cross-Strait Medical and Health Exchange Association. The objective was to develop an evidence-based diagnosis and treatment guideline for OA in China based on emerging new evidence. The guideline was registered at International Practice Guidelines Registry Platform (IPGRP-2018CN028). The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence and the strength of recommendations, and the RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist was followed to report the guideline. The guideline provides recommendations for the OA diagnosis, disease risks monitoring and evaluate, treatment purpose and physical, medical and surgical interventions. This guideline is intended to serve as a tool for Chinese clinicians for the best decisions-making on diagnosis and treatment of OA.
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http://dx.doi.org/10.21037/atm-20-4665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607097PMC
October 2020

Rhein Derivatives, A Promising Pivot?

Mini Rev Med Chem 2021 ;21(5):554-575

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China.

Rhein, an anthraquinone derivative, has been employed widely, especially for the treatment of intractable diseases like diabetic nephropathy, arthritis, and cancer in a unique action mechanism. In the last decades, considerable efforts have been made in structural modification of rhein. This paper reviewed patents on pharmacological activity and therapeutic application of rhein and its derivatives from 1978 to 2018. Particularly, an analysis of patents was made, with the top 10 most valuable patents presented, and the interpretation of the legal status of patents was given. Given the properties of superior pharmacological activity, rich resources, cheap price, low toxicity, and mature extraction process, it is believed that an in-depth investigation on rhein and its derivatives is worth trying.
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http://dx.doi.org/10.2174/1389557520666201109120855DOI Listing
July 2021

Development and formulation of the classification criteria for osteoarthritis.

Ann Transl Med 2020 Sep;8(17):1068

Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, China.

Background: The classification criteria of osteoarthritis (OA) is lack of the support of relevant research evidence and there is no standardized protocol for detailed steps of the development or clinical verification of classification criteria has yet been established. This study aims to describe the development process of the Categorization of Osteoarthritis CHecklist (COACH), which is designed to choose the precise treatment option for patients with OA.

Methods: A multidisciplinary panel was established to gather opinions. We conducted questionnaire survey and literature review to generate and COACH Panel members were invited to review the drafted classification criteria and optimize classification criteria. The final list of items was discussed and reached the agreement by the core group of the panel.

Results: Thirty-six experts participated in COACH Panel including rheumatologist (80.6%; 29/36), orthopedist (13.9%; 5/36), methodologist (2.8%; 1/36) and rehabilitation physician (2.8%; 1/36) for classification factors generating and optimizing. The main body of the final classification criteria consists of six types of OA pathogenesis, eight types of medical findings (which can be grouped into two categories), and six types of the location. The final criteria include load-based type, structure-based type, inflammation-based type, metabolic-based type, systemic factor based type and mixed type.

Conclusions: COACH can better help clinicians quickly classify OA patients and help to choose the best treatment option from the aspects of types, findings and locations. What's more, the classification criteria are also helpful to promote the basic medical research and targeted prevention of OA.
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http://dx.doi.org/10.21037/atm-20-4673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575945PMC
September 2020

Effects of infrapatellar fat pad preservation versus resection on clinical outcomes after total knee arthroplasty in patients with knee osteoarthritis (IPAKA): study protocol for a multicentre, randomised, controlled clinical trial.

BMJ Open 2020 10 23;10(10):e043088. Epub 2020 Oct 23.

Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China

Introduction: The infrapatellar fat pad (IPFP) is commonly resected during total knee arthroplasty (TKA) for better exposure. However, our previous studies have suggested that IPFP size was protective against, while IPFP signal intensity alteration was detrimental on knee symptoms and structural abnormalities. We hypothesise that an IPFP with normal qualities, rather than abnormal qualities, should be preserved during TKA. The aim of this study is to compare, over a 1-year period, the postoperative clinical outcomes of IPFP preservation versus resection after TKA in patients with normal or abnormal IPFP signal intensity alteration on MRI.

Methods And Analysis: Three hundred and sixty people with end-stage knee osteoarthritis and on the waiting list for TKA will be recruited and identified as normal IPFP quality (signal intensity alteration score ≤1) or abnormal IPFP quality (signal intensity alteration score ≥2). Patients in each hospital will then be randomly allocated to IPFP resection group or preservation group. The primary outcomes are the summed score of self-reported Knee Injury and Osteoarthritis Outcome Score (KOOS), KOOS subscales assessing function in daily activities and function in sport and recreation. Secondary endpoints will be included: KOOS subscales (pain, symptoms and quality of life), Knee Society Score, 100 mm Visual Analogue Scale (VAS) Pain, timed up-and-go test, patellar tendon shortening, 100 mm VAS self-reported efficacy of reduced pain and increased quality of life, and Insall-Salvati index assessed on plain X-ray. Adverse events will be recorded. Intention-to-treat analyses will be used.

Ethics And Dissemination: The study is approved by the local Medical Ethics Committee (Zhujiang Hospital Ethics Committee, reference number 2017-GJGBK-001) and will be conducted according to the principle of the Declaration of Helsinki (64th, 2013) and the Good Clinical Practice standard, and in compliance with the Medical Research Involving Human Subjects Act . Data will be published in peer-reviewed journals and presented at conferences, both nationally and internationally.

Trial Registration Number: This trial was registered at Clinicaltrial.gov website on 19 October 2018 with identify number NCT03763448.
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http://dx.doi.org/10.1136/bmjopen-2020-043088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590360PMC
October 2020

Physical Distancing Measures and Walking Activity in Middle-aged and Older Residents in Changsha, China, During the COVID-19 Epidemic Period: Longitudinal Observational Study.

J Med Internet Res 2020 10 26;22(10):e21632. Epub 2020 Oct 26.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.

Background: Physical distancing measures taken to contain COVID-19 transmission may substantially reduce physical activity levels and cause individuals to adopt a more sedentary lifestyle.

Objective: The objective of this study is to determine if there was any change in daily steps, an important component of daily physical activity, and examine risk factors for frequent low daily steps during the COVID-19 epidemic.

Methods: We used data collected from the Step Study, a population-based longitudinal study of walking activity among residents aged ≥40 years in Changsha, China. Daily steps were collected via a smartphone linked to WeChat, a social networking platform. We plotted mean daily steps and the prevalence of low daily steps (≤1500 steps/day) 30 days before (reference period) and 30 days after (epidemic period) January 21, 2020 (date of the first COVID-19 case diagnosed in Changsha), and compared it with the same corresponding period from 2019. We examined the association of risk factors with the prevalence of frequent low daily steps (≤1500 steps/day for ≥14 days) using logistic regression.

Results: Among 3544 participants (mean age 51.6 years; n=1226 females, 34.6%), mean daily steps dropped from 8097 to 5440 and the prevalence of low daily steps increased from 3% (2287/76,136 person-day) to 18.5% (12,951/70,183 person-day) during the reference and epidemic periods, respectively. No such phenomenon was observed during the corresponding period in 2019. Older age (P for interaction=.001) and female sex (P for interaction<.001) were both associated with a higher prevalence of frequent low daily steps and were more pronounced during the epidemic period. More education was associated with a lower prevalence of frequent low daily steps during the reference period but not the epidemic period (P for interaction=.34). Body mass index or comorbidity were not associated with frequent low daily steps during either period.

Conclusions: Daily steps of Changsha residents aged ≥40 years dropped significantly during the COVID-19 period, especially among older adults and females. Although successful physical distancing, measured by the rapid downward trend in daily step counts of residents, played a critical role in the containment of the COVID-19 epidemic, our findings of an increase in the prevalence of frequent low daily steps raise concerns about unintended effects on physical activity.
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http://dx.doi.org/10.2196/21632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592463PMC
October 2020

Stimulation of in vitro and in vivo osteogenesis by Ti-Mg alloys with the sustained-release function of magnesium ions.

Colloids Surf B Biointerfaces 2021 Jan 18;197:111360. Epub 2020 Sep 18.

School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore, 639798, Singapore.

Magnesium (Mg) is well-known for its bioactivity and degradability. However, due to its low evaporation temperature and limited solubility in titanium (Ti), the fabrication of Ti-Mg alloys remains a huge challenge. In this study, Ti-xMg (x = 0.312, 0.625, 1.25 and 2.5 wt.%) alloys were fabricated by the combination of mechanical alloying (MA) and spark plasma sintering (SPS). Mg mainly existed as a solid solute element in the Ti matrix, while it also existed as second-phase particles due to its precipitation and dispersion during the SPS process. At a low content of 0.625 wt.%, Mg could increase the mechanical strength of Ti by the solid solution strengthening. However, it was detrimental to material mechanical properties when the Mg content increased to 1.25 wt.%. Being immersed in phosphate buffered solution (PBS), Ti-Mg alloys exhibited a burst Mg release behavior within the first day, and then the rates of Mg release gradually decreased within the following 27 days. The results suggested that the cell viability was dependent on the content of Mg in the Ti-Mg alloys. The high Mg content (2.5 wt.%) in the Ti-Mg alloys could lead to significant cytotoxicity. However, appropriate Mg content (0.312∼0.625 wt.%) could promote cell attachment, proliferation and differentiation. The Ti-0.625Mg alloy exhibited the best in vitro biological performance among all groups. In vivo results obtained by implanting the Ti-0.625Mg alloy in the femurs of rats further revealed its enhanced regenerative potential and osteointegration compared to pure Ti implants.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111360DOI Listing
January 2021

Risk of venous thromboembolism in knee, hip and hand osteoarthritis: a general population-based cohort study.

Ann Rheum Dis 2020 12 16;79(12):1616-1624. Epub 2020 Sep 16.

Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Objectives: Osteoarthritis is a leading cause of immobility and joint replacement, two strong risk factors for venous thromboembolism (VTE). We aimed to examine the relation of knee, hip and hand osteoarthritis to the risk of VTE and investigate joint replacement as a potential mediator.

Methods: We conducted three cohort studies using data from The Health Improvement Network. Up to five individuals without osteoarthritis were matched to each case of incident knee (n=20 696), hip (n=10 411) or hand (n=6329) osteoarthritis by age, sex, entry time and body mass index. We examined the relation of osteoarthritis to VTE (pulmonary embolism and deep vein thrombosis) using a multivariable Cox proportional hazard model.

Results: VTE developed in 327 individuals with knee osteoarthritis and 951 individuals without osteoarthritis (2.7 vs 2.0 per 1000 person-years), with multivariable-adjusted HR being 1.38 (95% CI 1.23 to 1.56). The indirect effect (HR) of knee osteoarthritis on VTE through knee replacement was 1.07 (95% CI 1.01 to 1.15), explaining 24.8% of its total effect on VTE. Risk of VTE was higher in hip osteoarthritis than non-osteoarthritis (3.3 vs 1.8 per 1000 person-years; multivariable-adjusted HR=1.83, 95% CI 1.56 to 2.13). The indirect effect through hip replacement yielded an HR of 1.14 (95% CI 1.04 to 1.25), explaining 28.1% of the total effect. No statistically significant difference in VTE risk was observed between hand osteoarthritis and non-osteoarthritis (1.5 vs 1.6 per 1000 person-years; multivariable-adjusted HR=0.88, 95% CI 0.67 to 1.16).

Conclusion: Our large population-based cohort study provides the first evidence that knee or hip osteoarthritis, but not hand osteoarthritis, was associated with an increased risk of VTE, and such an association was partially mediated through knee or hip replacement.
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http://dx.doi.org/10.1136/annrheumdis-2020-217782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677492PMC
December 2020

DEPTOR Prevents Osteoarthritis Development Via Interplay With TRC8 to Reduce Endoplasmic Reticulum Stress in Chondrocytes.

J Bone Miner Res 2021 02 24;36(2):400-411. Epub 2020 Sep 24.

State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Endoplasmic reticulum (ER) stress has been shown to promote chondrocyte apoptosis and osteoarthritis (OA) progression, but the precise mechanisms via which ER stress is modulated in OA remain unclear. Here we report that DEP domain-containing mTOR-interacting protein (DEPTOR) negatively regulated ER stress and OA development independent of mTOR signaling. DEPTOR is ubiquitinated in articular chondrocytes and its expression is markedly reduced along with OA progression. Deletion of DEPTOR in chondrocytes significantly promoted destabilized medial meniscus (DMM) surgery-induced OA development, whereas intra-articular injection of lentivirus-expressing DEPTOR delayed OA progression in mice. Proteomics analysis revealed that DEPTOR interplayed with TRC8, which promoted TRC8 auto-ubiquitination and degraded by the ubiquitin-proteasome system (UPS) in chondrocytes. Loss of DEPTOR led to TRC8 accumulation and excessive ER stress, with subsequent chondrocyte apoptosis and OA progression. Importantly, an inhibitor of ER stress eliminated chondrocyte DEPTOR deletion-exacerbated OA in mice. Together, these findings establish a novel mechanism essential for OA pathogenesis, where decreasing DEPTOR in chondrocytes during OA progression relieves the auto-ubiquitination of TRC8, resulting in TRC8 accumulation, excessive ER stress, and OA progression. Targeting this pathway has promising therapeutic potential for OA treatment. © 2020 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4176DOI Listing
February 2021

Inflammatory potential of diet and risk of incident knee osteoarthritis: a prospective cohort study.

Arthritis Res Ther 2020 09 10;22(1):209. Epub 2020 Sep 10.

Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA, 02114, USA.

Background: To examine the relation between inflammatory potential of diet and incident knee osteoarthritis (OA) and the role of BMI in the association of interest.

Methods: In the Osteoarthritis Initiative, the energy-adjusted dietary inflammatory index (E-DII™) scores were calculated based on the Block Brief 2000 Food Frequency Questionnaire and categorized into sex-specific quartiles. Outcomes were incident (1) radiographic knee OA (ROA) (i.e., a KL grade ≥ 2) and (2) symptomatic knee OA (SxOA) (i.e., a combination of frequent knee pain and ROA). We fitted generalized estimating equation models to examine the association between E-DII scores and incident knee OA. We performed mediation analyses to assess the potential mediation by BMI in the DII-OA relation.

Results: Over a 48-month follow-up period, 232 and 978 knees developed ROA and SxOA, respectively. Compared with the lowest (most anti-inflammatory) E-DII quartile, the odds ratio (OR) of incident ROA for the highest (most pro-inflammatory) E-DII quartile was 1.73 (95% confidence interval (CI) 1.15 to 2.62, P = 0.007). The corresponding OR for SxOA was 1.43 (95% CI 1.16 to 1.76, P = 0.001). The DII-OA association was significantly mediated via BMI with an indirect effect of 1.08 (95% CI 1.04, 1.13) for ROA and 1.13 (95% CI 1.09, 1.16) for SxOA, accounting for 20.4% and 44.5% of the total effect, respectively.

Conclusions: A higher inflammatory potential of diet increased the risk of knee OA. The association was significantly mediated via BMI. Targeting the inflammatory potential of diet may be beneficial to reduce the risk of knee OA.
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http://dx.doi.org/10.1186/s13075-020-02302-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488131PMC
September 2020

Experimental study and reflection on peacetime and wartime reconstruction of large general hospitals in public health emergencies.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2020 May;45(5):489-494

Department of Hospital Infection Control Center, Xiangya Hospital, Changsha 410008.

To propose the architectural layout for the big general hospital in the face of public health emergencies, we analyzed the conditions, methods, problems and countermeasures for the reconstruction of the isolation ward from the existing medical building layout of a general hospital. The affected areas met the requirements of isolation ward in the reconstruction, and realized the corresponding partition and separation of people. But the cost of occupying the medical room should be concerned. General hospital should be alerted to potential risks of public health emergencies. The characteristics of different construction types, defects, and the function of the hospital should be considered in the construction, rebuilding, and expansion of the hospital, which shouldnot only meet the needs of the development of the hospital daily usage but also consider dealing with emergent public health events. We can adopt the reasonable layout, including setting up a firewall-like device between the channel and the floor, an ordinary ward at ordinary times, and an independent space for emergency by pulling down the gate. This strategy can not only avoid the problem of low utilization rate of the space occupied by the corresponding area in the ward for diseases spread by air and droplets, maximizing the efficiency of the medical site, but also avoid the problem of emergency response to the temporary reconstruction.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2020.200401DOI Listing
May 2020

Delayed Denosumab Injections and Fracture Risk Among Patients With Osteoporosis : A Population-Based Cohort Study.

Ann Intern Med 2020 10 28;173(7):516-526. Epub 2020 Jul 28.

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (D.H.S.).

Background: Denosumab is effective for osteoporosis, but discontinuation leads to rapid reversal of its therapeutic effect.

Objective: To estimate the risk for fracture among users of denosumab who delayed subsequent doses compared with users who received doses on time.

Design: Population-based cohort study.

Setting: The Health Improvement Network U.K. primary care database, 2010 to 2019.

Patients: Persons aged 45 years or older who initiated denosumab therapy for osteoporosis.

Measurements: Observational data were used to emulate an analysis of a hypothetical trial with 3 dosing intervals: subsequent denosumab injection given within 4 weeks after the recommended date ("on time"), delay by 4 to 16 weeks ("short delay"), and delay by more than 16 weeks ("long delay"). The primary outcome was a composite of all fracture types at 6 months after the recommended date. Secondary outcomes were major osteoporotic fracture, vertebral fracture, hip fracture, and nonvertebral fracture.

Results: Investigators identified 2594 patients initiating denosumab therapy. The risk for composite fracture over 6 months was 27.3 in 1000 for on-time dosing, 32.2 in 1000 for short delay, and 42.4 in 1000 for long delay. Compared with on-time injections, short delay had a hazard ratio (HR) for composite fracture of 1.03 (95% CI, 0.63 to 1.69) and long delay an HR of 1.44 (CI, 0.96 to 2.17) ( for trend = 0.093). For vertebral fractures, short delay had an HR of 1.48 (CI, 0.58 to 3.79) and long delay an HR of 3.91 (CI, 1.62 to 9.45).

Limitation: Dosing schedules were not randomly assigned.

Conclusion: Although delayed administration of subsequent denosumab doses by more than 16 weeks is associated with increased risk for vertebral fracture compared with on-time dosing, evidence is insufficient to conclude that fracture risk is increased at other anatomical sites with long delay.

Primary Funding Source: National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation.
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http://dx.doi.org/10.7326/M20-0882DOI Listing
October 2020

Initial analgesic prescriptions for osteoarthritis in the United Kingdom, 2000-2016.

Rheumatology (Oxford) 2021 01;60(1):147-159

Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital.

Objectives: To examine trends in the initial prescription of commonly-prescribed analgesics and patient- as well as practice-level factors related to their selection in incident OA.

Methods: Patients consulting with incident clinical OA between 2000-2016 were identified within The Health Improvement Network in the United Kingdom (UK) general practice. Excluded were patients who had history of cancer or were prescribed the analgesics of interest within 6 months before diagnosis of OA. Initial analgesic prescription included oral non-selective NSAID, oral selective cyclooxygenase-2 inhibitor, topical NSAID, paracetamol, topical salicylate or oral/transdermal opioid within 1 month after OA diagnosis.

Results: ∼44% of patients with incident OA (n = 125 696) were prescribed one of these analgesics. Incidence of oral NSAID prescriptions decreased whereas other analgesic prescriptions, including oral opioid prescriptions, increased (all P-for-trend < 0.001). Patients with a history of gastrointestinal disease were more likely to receive topical NSAIDs, paracetamol or oral/transdermal opioids. Only 38% of patients with history of gastrointestinal disease and 21% of patients without it had co-prescription of gastroprotective agent with oral NSAIDs. Oral/transdermal opioid prescription was higher among the elderly (≥65 years), women, obesity, current smoker, and patients with gastrointestinal, cardiovascular or chronic kidney disease. Prescription of oral opioids increased with social deprivation (P-for-trend < 0.05) and was highest in Scotland, whereas transdermal opioid prescription was highest in Northern Ireland (all P-for-homogeneity-test < 0.05).

Conclusion: The initial prescription pattern of analgesics for OA has changed over time in the UK. Co-prescription of gastroprotective agents with oral NSAIDs remains suboptimal, even among those with prior gastrointestinal disease.
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http://dx.doi.org/10.1093/rheumatology/keaa244DOI Listing
January 2021

Association between proton pump inhibitors use and risk of hip fracture: A general population-based cohort study.

Bone 2020 10 25;139:115502. Epub 2020 Jun 25.

Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

Previous studies comparing risk of fracture among Proton Pump Inhibitors (PPIs) users with that among non-users were susceptible to confounding by indication. Epidemiologic studies of this association using an active medication as a comparator would appropriately address this bias. We conducted a propensity-score matched cohort study to compare the risk of incident fracture over five years among initiators of PPIs with initiators of histamine 2 receptor antagonist (H2RA) using data collected from The Health Improvement Network (THIN) database in the United Kingdom (2000-2016). The prevalence of PPIs prescription increased 3.8-fold from 2000 (7.9%) to 2012 (30.3%) and remained stable since then. Of the 50,265 propensity-score matched participants in each cohort (mean age was 65 years, and 57% were women), 370 (1.9/1000 person-years) incident hip fracture occurred in the PPIs initiators and 294 (1.5/1000 person-years) in the H2RA initiators during the follow-up period. The rate difference of incident hip fracture for PPIs initiation was 0.4 (95% confidence interval [CI]: 0.2-0.7)/1000 person-years compared with H2RA initiation and the corresponding hazard ratio (HR) was 1.27 (95%CI: 1.09-1.48). Compared with non-PPI use, multivariable-adjusted odds ratios (ORs) of hip fracture were 1.17 (95%CI: 0.94-1.46), 1.55 (95%CI: 1.23-1.96), and 1.67 (95%CI: 1.33-2.10) for 1-2, 3-9 and ≥ 10 prescriptions of PPIs, respectively (P for trend = 0.001). We found that PPIs prescription has been increasing rapidly over the past decade in the United Kingdom, and the initiation of PPIs was associated with a higher risk of hip fracture than initiation of H2RA.
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http://dx.doi.org/10.1016/j.bone.2020.115502DOI Listing
October 2020

Corrigendum to: Statin use and risk of joint replacement due to osteoarthritis and rheumatoid arthritis: a propensity-score matched longitudinal cohort study.

Rheumatology (Oxford) 2020 10;59(10):3120

Academic Rheumatology Department, Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.

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http://dx.doi.org/10.1093/rheumatology/keaa223DOI Listing
October 2020

Comparative Risk-Benefit Profiles of Individual Devices for Graft Fixation in Anterior Cruciate Ligament Reconstruction: A Systematic Review and Network Meta-analysis.

Arthroscopy 2020 07 29;36(7):1953-1972. Epub 2020 Apr 29.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China. Electronic address:

Purpose: To compare the efficacy and safety of individual devices for femoral and/or tibial graft fixation in anterior cruciate ligament (ACL) reconstruction.

Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to December 12, 2018. Randomized controlled trials comparing individual devices for ACL graft fixation were included. Bayesian network meta-analysis was performed to assess the efficacy profile using the following outcomes: Lysholm score, International Knee Documentation Committee (IKDC) category, laxity, range of motion, and Tegner score. The incidence of infection, effusion, and graft rupture for each device was reported.

Results: We included 57 randomized controlled trials involving 4,304 patients aged 23.8 to 40.9 years. The female proportion ranged from 0% to 100%. The length of follow-up ranged from 6 to 144 months. Of the 13 studied femoral fixation devices, none was significantly different from the others regarding the Lysholm score, IKDC category, range of motion, and Tegner score. Bioabsorbable interference screws (standardized mean difference, 1.3; 95% credible interval, 0.0-2.5) showed higher laxity than the EndoPearl at a borderline level of statistical significance, but the difference varied substantially within multiple sensitivity analyses. Infection (2.0%) was most commonly seen with the EndoPearl, whereas the bone mulch screw had the highest incidence of effusion (5.5%) and graft rupture (5.5%). For the 9 studied tibial fixation devices, no significant difference was observed in the aforementioned efficacy measurements. Bioabsorbable interference screws with staples had the highest incidence of infection (11.1%) and effusion (15.6%), whereas graft rupture was most commonly seen with the bone plug (4.0%).

Conclusions: Graft fixation devices in ACL reconstruction share a similar efficacy profile in terms of the Lysholm score, IKDC category, range of motion, and Tegner score but not laxity. On the other hand, safety profiles seem to vary among different devices. These findings can support surgeons, alongside their experience and preference, as well as the relative cost of each device, in delivering an individualized plan for an optimal operation.

Level Of Evidence: Level II, meta-analysis of Level I and II studies.
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http://dx.doi.org/10.1016/j.arthro.2020.04.023DOI Listing
July 2020

Epiphyseal Cartilage Formation Involves Differential Dynamics of Various Cellular Populations During Embryogenesis.

Front Cell Dev Biol 2020 5;8:122. Epub 2020 Mar 5.

Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.

A joint connects two or more bones together to form a functional unit that allows different types of bending and movement. Little is known about how the opposing ends of the connected bones are developed. Here, applying various lineage tracing strategies we demonstrate that progenies of Gdf5-, Col2-, Prrx1-, and Gli1-positive cells contribute to the growing epiphyseal cartilage in a spatially asymmetrical manner. In addition, we reveal that cells in the cartilaginous anlagen are likely to be the major sources for epiphyseal cartilage. Moreover, Gli1-positive cells are found to proliferate along the skeletal edges toward the periarticular region of epiphyseal surface. Finally, a switch in the mechanism of growth from cell division to cell influx likely occurs in the epiphyseal cartilage when joint cavitation has completed. Altogether, our findings reveal an asymmetrical mechanism of growth that drives the formation of epiphyseal cartilage ends, which might implicate on how the articular surface of these skeletal elements acquires their unique and sophisticated shape during embryonic development.
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http://dx.doi.org/10.3389/fcell.2020.00122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066500PMC
March 2020

Statin use and risk of joint replacement due to osteoarthritis and rheumatoid arthritis: a propensity-score matched longitudinal cohort study.

Rheumatology (Oxford) 2020 10;59(10):2898-2907

Academic Rheumatology Department, Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.

Objective: Statins are reported to have a potential benefit on progression of OA and on disease activity in RA, but existing evidence is conflicting. Our objective was to examine whether statins associate with reduction in the risk for joint replacement due to OA and RA.

Methods: This was a propensity score-matched cohort study. Electronic health records from the UK Clinical Practice Research Datalink were used. We selected people prescribed statins and people never prescribed statins. Each statin user was matched to a non-user by age, gender, practice and propensity score for statin prescription. The main outcome measures were knee or hip joint replacement overall, and specifically because of OA or RA. The association between statins and risk of joint replacement was assessed using Cox proportional hazard regression. Statin exposure was categorized according to the potency of reducing low-density lipoprotein as low (21-28%), medium (32-38%) or high (42-55%) intensity.

Results: A total of 178 467 statin users were matched with 178 467 non-users by age, gender, practice and propensity score. Overall, statin was not associated with reduced risk of knee or hip replacement (hazard ratio 0.99, 95% CI: 0.97, 1.03), unless prescribed at high strength (0.86, 0.75-0.98). The reduced risk was only observed for joint replacement due to RA (0.77, 0.63-0.94) but not OA (0.97, 0.94-1.01).

Conclusion: Statins at high intensity may reduce the risk of hip or knee replacement. This effect may be RA specific. Further studies to investigate mechanisms of risk reduction and the impact in people with RA are warranted.
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http://dx.doi.org/10.1093/rheumatology/keaa044DOI Listing
October 2020
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