Dan Xing

Osteoarthritis and all-cause mortality in worldwide populations: grading the evidence from a meta-analysis.

The objective of this study is to investigate the association between osteoarthritis (OA) and all-cause mortality in worldwide populations and to develop recommendations according to GRADE evidence levels. Literature search through Nov 2015 was performed using the electronic databases (including MEDLINE, EMBASE, EBSCO and Cochrane library). The prospective cohort trials that investigated the association between the symptomatic OA (SxOA) or radiological OA (ROA) and all-cause mortality were identified. Hazard ratios (HR) of all-cause mortality in patients with RxOA or ROA were pooled respectively. The evidence quality was evaluated using the GRADE system, while the recommendations were taken according to the quality. Nine of the published literature met the eligible criteria. Meta-analysis revealed that there was no significant difference in the association between SxOA and all-cause mortality (HR = 0.91, 95% CI: 0.68–1.23) and between ROA and all-cause mortality (HR = 1.13, 95% CI: 0.95–1.35). The overall GARDE evidence quality was very low, which will lower our confidence in taking recommendations. To summarize, there was no reliable and confident evidence existed currently in respect of the association between OA and all-cause mortality. Due to the very low level of evidence quality currently, high-quality studies are still required.

Intra-articular Hyaluronic Acid in Treating Knee Osteoarthritis: a PRISMA-Compliant Systematic Review of Overlapping Meta-analysis

Numerous meta-analyses have been conducted aiming to compare hyaluronic acid (HA) and placebo in treating knee osteoarthritis (OA). Nevertheless, the conclusions of these meta-analyses are not in consistency. The purpose of the present study was to perform a systematic review of overlapping meta-analyses investigating the efficacy and safety of HA for Knee OA and to provide treatment recommendations through the best evidence. A systematic review was conducted based on the PRISMA guidelines. The meta-analyses and/or systematic reviews that compared HA and placebo for knee OA were identified. AMSTAR instrument was used to evaluate the methodological quality of individual study. The information of heterogeneity within each variable was fetched for the individual studies. Which meta-analyses can provide best evidence was determined according to Jadad algorithm. Twelve meta-analyses met the eligibility requirements. The Jadad decision making tool suggests that the highest quality review should be selected. As a result, a high-quality Cochrane review was included. The present systematic review of overlapping meta-analyses demonstrates that HA is an effective intervention in treating knee OA without increased risk of adverse events. Therefore, the present conclusions may help decision makers interpret and choose among discordant meta-analyses.

Mesenchymal stem cells injections for knee osteoarthritis: a systematic overview

Numerous systematic reviews investigating the effects of mesenchymal stem cells (MSCs) in treating knee osteoarthritis (OA) have been published with controversial conclusion. The purpose of the overview was (1) to perform an overview of systematic reviews investigating MSCs for knee OA and (2) to synthesize evidence qualitatively to assess confidence in the review findings. A systematic search of systematic reviews published through Aug 2017 was conducted using the MEDLINE, EMBASE and Cochrane Library. The methodological quality and risk of bias of included systematic reviews was assessed by AMSTAR instrument and ROBIS tool, respectively. Best evidence choice procedure was conducted according to the Jadad decision algorithm. The systematic reviews with high methodological quality and low risk of bias were selected ultimately for further evidence synthesis based on the CERQual tool. Four systematic reviews were eligible for inclusion. According to the ROBIS tool, there was one systematic review with low risk of bias and three with high risk of bias. Thus, only one systematic review conducted by Pas et al. with highest AMSTAR score and low risk of bias was selected. For all outcomes after evidence synthesis via the CERQual tool, confidence for decision making was either low (self-reported measurement and MRI/histological outcome) or moderate (adverse events). The present study demonstrates that moderate confidence could be placed in safety of MSCs therapy for knee OA, but with low confidence in efficacy outcomes due to limitations of the current evidence. Further high-quality studies with high internal and external validity are still required.

Intra-articular injection of mesenchymal stem cells in treating knee osteoarthritis: a systematic review of animal studies

PURPOSE Mesenchymal stem cells (MSCs) injection has emerged as a novel treatment for knee osteoarthritis (KOA) but with inconsistent results in the experimental studies. Thus, the purpose of the present study is to evaluate the preclinical animal studies of MSCs injection for KOA and to determine the evidence for a role for MSCs in further clinical trials. METHODS A systematic search of KOA animal studies published through Aug 2017 was conducted using the PubMed, Embase and Web of science. Criteria for eligibility were animal studies assessing the therapeutic effects of MSCs intra-articular injection to animals with KOA. The methodological quality of included studies was assessed by the SYRCLE tool for assessing risk of bias in animal intervention studies. Descriptive synthesis was performed. Evidence quality was evaluated based on the Confidence in the Evidence from Reviews of Qualitative research (CERQual) tool. RESULTS Twenty-three KOA animal studies were eligible for inclusion. According to the SYRCLEs tool, all included studies had high risk of bias. Between-study heterogeneity was substantial. The included studies varied in terms of species, modeling methods, MSCs origin, treatment timing, injections frequency, transplantation type and dose of MSCs. The following outcomes, gross morphology, histological analysis, immunohistochemical analysis, radiological evaluation or behavior analysis, were reported in the primary studies. For all outcomes, the evidence quality was low or very low. CONCLUSIONS We do not have absolute confidence to recommend use MSCs injection for KOA clinical trials. Based on the internal and external validity of current animal studies, high quality experimental studies and efforts for effective translation from preclinical studies to clinical trials are still required.

A protocol for developing a clinical practice guideline for intra-articular injection for treating knee osteoarthritis

Introduction Osteoarthritis (OA) is the most prevalent disorder of articulating joints in humans. As one of the steps of advanced pharmacological management, intra-articular treatment is applied in knee OA. However, there is no clinical practice guideline (CPG) involving intra-articular injection for knee OA. Here, we will develop a CPG according to a recognized methodology. Methods and analysis We will develop the new CPG according to the Institute of Medicine, the Appraisal of Guidelines for Research & Evaluation Ⅱ (AGREE Ⅱ), and WHO guideline handbook and make recommendations based on systematic reviews. We will establish a Guideline Working Group (including a Guideline Steering Subgroup, a Guideline Development Subgroup, and a Guideline Secretary Subgroup); formulate clinical questions in the form of Population, Intervention, Comparison, Outcomes (PICO); and complete a literature search. The consensus will be developed through evidence syntheses and the Delphi method. We will also consider patients’ values or preferences, peer review results, and declaration of interests in developing CPG. The present CPG was registered on the International Practice Guidelines Registry Platform (http://www.guidelines-registry.org/), and the registration number is IPGRP-2016CN004. Ethics and dissemination The protocol will provide us a roadmap to systematically develop evidence-based CPG for intra-articular injection for knee OA. The work will be disseminated electronically and in print. The guideline would be the first CPG that is developed primarily by orthopedic specialists in China and strictly based on systematic methodology.

Injectable nanohydroxyapatite-chitosan-gelatin micro-scaffolds induce regeneration of knee subchondral bone lesions

Subchondral bone has been identified as an attractive target for KOA. To determine whether a minimally invasive micro-scaffolds could be used to induce regeneration of knee subchondral bone lesions, and to examine the protective effect of subchondral bone regeneration on upper cartilage, a ready-to-use injectable treatment with nanohydroxyapatite-chitosan-gelatin micro-scaffolds (HaCGMs) is proposed. Human-infrapatellar-fat-pad-derived adipose stem cells (IPFP-ASCs) were used as a cellular model to examine the osteo-inductivity and biocompatibility of HaCGMs, which were feasibly obtained with potency for multi-potential differentiations. Furthermore, a subchondral bone lesion model was developed to mimic the necrotic region removing performed by surgeons before sequestrectomy. HaCGMs were injected into the model to induce regeneration of subchondral bone. HaCGMs exhibited desirable swelling ratios, porosity, stiffness, and bioactivity and allowed cellular infiltration. Eight weeks after treatment, assessment via X-ray imaging, micro-CT imaging, and histological analysis revealed that rabbits treated with HaCGMs had better subchondral bone regeneration than those not treated. Interestingly, rabbits in the HaCGM treatment group also exhibited improved reservation of upper cartilage compared to those in other groups, as shown by safranin O-fast green staining. Present study provides an in-depth demonstration of injectable HaCGM-based regenerative therapy, which may provide an attractive alternative strategy for treating KOA.

Intra-articular platelet-rich plasma injections for knee osteoarthritis: An overview of systematic reviews and risk of bias considerations

Numerous systematic reviews investigating the efficacy of platelet‐rich plasma (PRP) in treating knee osteoarthritis (OA) have been recently published. The purpose of the present study was (1) to perform an overview of overlapping systematic reviews investigating PRP for knee OA via evaluating methodological quality and risk of bias of systematic reviews and (2) to provide recommendations through the best evidence.

Valgus malalignment and prevalence of lateral compartmental radiographic knee osteoarthritis(OA): the wuchuan oa study

Author(s): Wang, Bin; Liu, Qiang; Wise, Barton L; Ke, Yan; Xing, Dan; Xu, Yuankun; Zhang, Yuqing; Lin, Jianhao | Abstract: AIM:To evaluate whether knee alignment explains the higher prevalence of lateral compartment tibiofemoral radiographic osteoarthritis (TFROA) among rural Chinese compared with that among Whites. METHODS:The Wuchuan OA Study is a population-based longitudinal study of risk factors for knee OA. At baseline 1030 participants had home interviews, clinical examinations and weight-bearing posteroanterior semi-flexed radiographs of the tibiofemoral joints. Anatomic knee alignment was measured using an e-film workstation and divided into three categories: normal (182°-184°), valgus (g 184°), and varus (l 182°) alignment. A knee was defined as having medial or lateral compartmental ROA if its Kellgren and Lawrence grade was ≥ 2 and joint space narrowing ≥ 1 in the medial or lateral compartment, respectively. We examined the association between knee alignment with prevalent medial or lateral knee ROA separately using multiple logistic regression. RESULTS:Among 1030 participants, the proportions of knees with normal, valgus and varus alignment were 29.9%, 56.5% and 13.7%, respectively. The prevalence of medial and lateral ROA was 16.0% and 4.3%, respectively. Valgus alignment was associated with prevalence of lateral compartment ROA (odds ratio [OR] = 5.0, 95% CI: 2.4-10.5), while varus alignment was associated with medial compartment ROA (OR = 6.1, 95% CI: 4.4-8.6). The ratio of prevalence of lateral versus medial compartment TFROA was greater in Wuchuan than that in the Framingham OA Study and valgus malalignment was more common in Wuchuan than in the Rotterdam study. CONCLUSIONS:The prevalence of compartment-specific TFROA differs between rural Chinese and Whites. This difference is likely due to relatively high prevalence of valgus malalignment in rural Chinese compared with that in Whites.

Valgus malalignment and prevalence of lateral compartmental radiographic knee osteoarthritis (OA): The Wuchuan OA study

To evaluate whether knee alignment explains the higher prevalence of lateral compartment tibiofemoral radiographic osteoarthritis (TFROA) among rural Chinese compared with that among Whites.