Analysis of the causes of primary revision after unicompartmental knee arthroplasty: A case series.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) has great advantages in the treatment of unicompartmental knee osteoarthritis, but its revision rate is higher than that of total knee arthroplasty. AIM: To summarize and analyse the causes of revision after UKA. METHODS: This is a retrospective case series study in which the reasons for the first revision after UKA are summarized. We analysed the clinical symptoms, medical histories, laboratory test results, imaging examination results and treatment processes of the patients who underwent revision and summarized the reasons for primary revision after UKA. RESULTS: A total of 13 patients, including 3 males and 10 females, underwent revision surgery after UKA. The average age of the included patients was 67.62 years. The prosthesis was used for 3 d to 72 months. The main reasons for revision after UKA were improper suturing of the surgical opening (1 patient), osteophytes (2 patients), intra-articular loose bodies (2 patients), tibial prosthesis loosening (2 patients), rheumatoid arthritis (1 patient), gasket dislocation (3 patients), anterior cruciate ligament injury (1 patient), and medial collateral ligament injury with residual bone cement (1 patient). CONCLUSION: The causes of primary revision after UKA were gasket dislocation, osteophytes, intra-articular loose bodies and tibial prosthesis loosening. Avoidance of these factors may greatly reduce the rate of revision after UKA, improve patient satisfaction and reduce medical burden.

Transcriptomic analyses and machine-learning methods reveal dysregulated key genes and potential pathogenesis in human osteoarthritic cartilage.

Aims: This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Methods: Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results: A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion: The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets.

Intravenous Tranexamic Acid Significantly Improved Visualization and Shortened the Operation Time in Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-analysis of Level I and II Studies.

PURPOSE: To further clarify the role of tranexamic acid (TXA) in arthroscopic rotator cuff repair (ARCR), especially visual field clarity and operation time. METHODS: We searched the PubMed, Cochrane Library, and Embase databases to find prospective randomized controlled clinical trials (RCTs) examining the use of TXA in ARCR. All included RCTs were evaluated for methodological quality using the Cochrane Collaboration's risk of bias tool. We used Review Manager 5.3 for meta-analysis and calculated the weighted mean difference (WMD) and 95% confidence interval (CI) of the related outcome indicators. The GRADE system was used to evaluate the strength of the clinical evidence provided by the included studies. RESULTS: Six RCTs (3 Level I, 3 Level II) from four countries or regions were included in this study: 2 studies used intra-articular (IA) TXA, and 4 studies used intravenous TXA. A total of 451 patients underwent ARCR, including 227 patients in the TXA group and 224 patients in the non-TXA group. In 2 RCTs evaluating good visualization, intravenous TXA achieved a better surgical field of view in ARCR compared to the control group (P =.036; P = .045). Meta-analysis showed that compared with non-TXA, intravenous TXA shortened the operation time (WMD = -12.87 min, 95% CI: -18.81 to -6.93). These two RCTs did not reveal a statistically significant difference in the impact of intravenous TXA and non-TXA on mean arterial pressure (MAP) (P = .306; P = .549). Compared with epinephrine (EPN), IA TXA had no significant effects on improving the visual field clarity under arthroscopy, shortening the operation time or reducing the total amount of irrigation fluid (P > .05). Compared with saline irrigation, IA TXA improved the surgical field of vision and shortened the operation time (P < .001). No adverse events were reported for either intravenous TXA or IA TXA. CONCLUSIONS: Intravenous TXA can shorten the operation time of ARCR, and the conclusions of existing RCTs suggest that intravenous TXA can improve visual field clarity during ARCR, thus supporting the application of intravenous TXA in ARCR. Compared with EPN, IA TXA was not better at improving the visual field clarity under arthroscopy and shortening the operation time, but it was better than saline irrigation. LEVEL OF EVIDENCE: Level II, systematic review and meta-analysis of Level I and II studies.

J-shaped association of serum uric acid concentrations with all-cause mortality in individuals with osteoarthritis: A prospective cohort study.

OBJECTIVE: The purpose of this study was to explore the relationship between serum uric acid (SUA) concentrations and all-cause mortality in individuals with osteoarthritis (OA). METHODS: All participant data were retrieved from the National Health and Nutrition Examination Survey database. A total of 4671 participants (age range: 20 to 85 years old), including 2988 females and 1683 males, were included in this study. The determination of death outcome was based on the National Death Index (up to December 31, 2019). We explored the nonlinear relationship between SUA concentrations and all-cause mortality in OA patients by establishing a Cox proportional risk model and a two-segment Cox proportional risk model and ran an interaction test to identify the high-risk population for all-cause mortality. RESULTS: During 30,645 person-years of follow-up, the number of all-cause deaths for females and males was 736 and 516, respectively. After multivariate adjustment, we found a nonlinear relationship between SUA concentrations and all-cause mortality in both females and males with OA. In addition, we found a J-shaped relationship between SUA concentrations and all-cause mortality. The SUA concentration thresholds for all-cause mortality of females and males were stable at 5.6mg/dl and 6.2mg/dl, respectively. Compared with SUA concentrations below the inflection point, the all-cause mortality risk at higher SUA concentrations in females and males with OA increased by 20% (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 1.1 to 1.2) and 25% (HR: 1.2, 95% CI: 1.12 to 1.39), respectively. CONCLUSIONS: There is a nonlinear relationship between SUA concentrations and all-cause mortality in the American OA population (J-shaped association). The all-cause mortality thresholds for SUA concentrations in females and males are 5.6mg/dl and 6.2mg/dl, respectively.

Higher systemic immune-inflammation index is associated with sarcopenia in individuals aged 18-59 years: a population-based study.

The association between the systemic immune-inflammation index (SII) and the risk of sarcopenia has not yet been revealed. The purpose of this study was to investigate the relationship between the SII and sarcopenia in individuals aged 18-59 years. All data for this study are from the National Health and Nutrition Examination Survey (NHANES) database, including 7258 participants (age range: 18-59 years). We divided SII values by quartiles (quartiles 1-4: 0.3-3.1, 3.2-4.4, 4.4-6.2, and 6.2-58.5). We constructed a multivariate logistic regression model to assess the association between the SII and the risk of sarcopenia, and an interaction test was run to test the stability of the model and identify high-risk individuals with sarcopenia. Compared to nonsarcopenia participants, sarcopenia patients had a significantly higher SII value (weighted average: 6.65 vs. 5.16) (P = 0.002). Multivariate logistic regression results showed a positive linear relationship between the SII and sarcopenia (OR [odds ratio] = 1.12, 95% CI [confidence interval] 1.03-1.21). Compared to the quartile 1 group, the quartile 4 group was associated with a higher risk of sarcopenia (OR = 3.94, 95% CI 1.42-10.94). Compared with the quartile 1 group, the OR value of the quartile 2 to quartile 4 groups showed an upwards trend (Ptrend < 0.001) as the level of SII increased. Subgroup analysis also indicate that the correlation between higher SII values and the risk of sarcopenia was stable. There was a significant positive linear relationship between SII and sarcopenia, indicating that higher SII values can increase the risk of sarcopenia in individuals aged 18-59 in the United States. The findings of this study will be beneficial in promoting the use of SII alone or in combination with other tools for the risk screening of sarcopenia in communities or large populations.

Longbie capsules reduce bone loss in the subchondral bone of rats with comorbid osteoporosis and osteoarthritis by regulating metabolite alterations.

Background and objective: With the development of global population aging, comorbidity (≥2 diseases) is a common health problem among elderly people. Osteoarthritis (OA) and osteoporosis (OP) are common in elderly individuals. There is a lack of drug therapy for OA and OP comorbidities. The purpose of this study was to explore the efficacy and mechanism of Longbie capsule (LBJN), which contains various plant herbs, in treating OA and OP comorbidities (OA + OP) in rats using metabolomics techniques. Methods: We created an OA + OP rat model through bilateral oophorectomy combined with meniscus instability surgery. Thirty SD rats were randomly divided into five groups (six in each group), namely, the sham group, OA group, OA + OP group, LBJN low-dose group (0.625 g/kg, OA + OP+LB-L group) and LBJN high-dose group (1.25 g/kg, OA + OP+LB-H group). After 8 weeks of intervention, we used micro-CT to detect bone microstructure status, ELISA to measure bone metabolism indicators, and UPLC-MS technology for metabolomics analysis. Finally, the screened differentially expressed metabolites were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and functional enrichment analysis. Results: The micro-CT results showed that LBJN significantly improved the bone mineral density (BMD) and bone quality of subchondral bone in OA + OP rats, and LBJN regulated the expression of bone alkaline phosphatase (BALP), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRACP) in serum to maintain bone metabolism balance. Metabolomics analysis showed that the metabolic trajectory of OA + OP rats after intervention in the OA + OP+LB-H group showed significant changes, and 107 potential biomarkers could be identified. Among them, 50 metabolites were upregulated (such as zeranol) and 57 were downregulated (such as vanillactic acid). The KEGG functional enrichment results indicated that the differentially expressed metabolites are mainly involved in amino acid metabolism, lipid metabolism, and carbohydrate metabolism. The KEGG pathway enrichment results indicated that LBJN may exert therapeutic effects on OA + OP rats by regulating the cAMP signaling pathway, and the FoxO signaling pathway. Conclusion: LBJN can maintain bone metabolism balance by regulating serum lipid metabolism, amino acid metabolism, carbohydrate metabolism, and estrogen, thereby reducing bone loss in subchondral bone, which may be a potential mechanism through which LBJN treats OA + OP.

Effects of resveratrol in an animal model of osteoporosis: a meta-analysis of preclinical evidence.

Background: Resveratrol is a natural polyphenol compound that is widely present in herbal medicines such as Reynoutria japonica Houtt., Veratrum nigrum L., and Catsiatora Linn and is used in traditional Chinese medicine to treat metabolic bone deseases. Animal experiments have shown that resveratrol may have a strong treatment effect against osteoporosis (OP). The purpose of this study was to explore the efficacy of resveratrol in treating OP animal models based on preclinical research data. Methods: This study was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases from inception to May 8, 2023, to identify animal experiments on the treatment of OP with resveratrol. The effect sizes of bone mineral density (BMD), parameters of micro-CT, serum calcium, phosphorus, alkaline phosphatase (ALP) and osteocalcin were expressed as the mean differences (MDs) and 95% confidence intervals (CIs). RevMan 5.4 software was used for data analysis. Results: This meta-analysis included a total of 15 animal experiments, including 438 OP rats. The meta-analysis results showed that compared with the control group, resveratrol (<10, 10-25, 40-50, ≥ 60 mg/kg/day) significantly increased femoral and lumbar bone mineral density (BMD) in OP rats (p < 0.05). Resveratrol (<10 mg/kg/day) significantly increased the BMD of the total body (MD = 0.01, 95% CI: 0.01 to 0.01, p < 0.001). In terms of improving the parameters related to micro-CT, resveratrol (40-50 mg/kg/day) can increase trabecular thickness and trabecular number and reduce trabecular spacing (p < 0.05). Compared with the control group, resveratrol can reduce the concentration of calcium and phosphorus in serum but has no significant effect on serum ALP and osteocalcin (p > 0.05). The results of subgroup analysis showed that resveratrol increased the whole-body BMD of SD rats (p = 0.002) but did not improve the whole-body BMD of 3-month-old rats (p = 0.17). Conclusion: Resveratrol can increase BMD in OP rat models, and its mechanism of action may be related to improving bone microstructure and regulating calcium and phosphorus metabolism. The clinical efficacy of resveratrol in the treatment of OP deserves further research.

Network pharmacology identifies fisetin as a treatment for osteoporosis that activates the Wnt/ß-catenin signaling pathway in BMSCs.

BACKGROUND: Although fisetin may exist widely in many natural herbs, its anti-OP mechanism is still unclear. The aim of this study is to explore the molecular anti-osteoporosis (OP) mechanism of fisetin based on network pharmacology and cell experiments. METHODS: The target of fisetin was extracted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The targets of OP were obtained by DisGeNET, GeneCards and the Comparative Toxicogenomics Database, and the targets of fisetin in OP were screened by cross-analysis. The protein-protein interaction (PPI) network was constructed by STRING, and the core targets were obtained. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on common targets via the Database for Annotation, Visualization and Integrated Discovery. Finally, an in vitro cell experiment was used to verify the anti-OP effect and mechanism of fisetin. RESULTS: There are 44 targets of fisetin related to the treatment of OP. The PPI results suggest that CTNNB1, CCND1, TP53, JUN, and AKT1 are the core targets. A total of 259 biological process, 57 molecular function and 26 cell component terms were obtained from GO enrichment analysis. The results of KEGG pathway enrichment analysis suggested that fisetin treatment of OP may be related to the Wnt signaling pathway, estrogen signaling pathway, PI3K-Akt signaling pathway and other signaling pathways. In vitro cell experiments showed that fisetin significantly increased the expression levels of ALP, collagen I, osteopontin and RUNX2 in bone marrow mesenchymal stem cells (BMSCs) (p < 0.05). Fisetin also increased the gene expression levels of Wnt3 and ß-catenin (CTNNB1) in BMSCs, which indicates that fisetin can regulate the Wnt/ß-catenin signaling pathway and promote the osteogenic differentiation of BMSCs. CONCLUSIONS: Fisetin acts on multiple targets and pathways in the treatment of OP; mechanistically, it regulates the Wnt/ß-catenin signaling pathway, which promotes the osteogenic differentiation of BMSCs and maintains bone homeostasis. The results of this study provide a theoretical basis for further study on the complex anti-OP mechanism of fisetin.

Risk factors for postoperative surgical site infections after anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

OBJECTIVES: The primary aim was to evaluate risk factors for surgical site infections after anterior cruciate ligament reconstruction (ACLR). The secondary aim was to investigate the surgical site infection incidence rate and the mean time to postoperative surgical site infection symptoms. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase and Web of Science were searched from database inception to September 2021 and updated in April 2022. ELIGIBILITY CRITERIA: Quantitative, original studies reporting potential risk factors for surgical site infections after ACLR were included. RESULTS: Twenty-three studies with 3871 infection events from 469 441 ACLRs met the inclusion criteria. Male sex (OR 1.78, p< 0.00001), obesity (OR 1.82, p=0.0005), tobacco use (OR 1.37, p=0.01), diabetes mellitus (OR 3.40, p=0.002), steroid use history (OR 4.80, p<0.00001), previous knee surgery history (OR 3.63, p=0.02), professional athlete (OR 4.56, p=0.02), revision surgery (OR 2.05, p=0.04), hamstring autografts (OR 2.83, p<0.00001), concomitant lateral extra-articular tenodesis (OR 3.92, p=0.0001) and a long operating time (weighted mean difference 8.12, p=0.005) were identified as factors that increased the risk of surgical site infections (superficial and deep) after ACLR. Age, outpatient or inpatient surgery, bone-patellar tendon-bone autografts or allografts and a concomitant meniscus suture did not increase the risk of surgical site infections. The incidence of surgical site infections after ACLR was approximately 1% (95% CI 0.7% to 1.2%). The mean time from surgery to the onset of surgical site infection symptoms was approximately 17.1 days (95% CI 13.2 to 21.0 days). CONCLUSION: Male sex, obesity, tobacco use, diabetes mellitus, steroid use history, previous knee surgery history, professional athletes, revision surgery, hamstring autografts, concomitant lateral extra-articular tenodesis and a long operation time may increase the risk of surgical site infections after ACLR. Although the risk of surgical site infections after ACLR is low, raising awareness and implementing effective preventions for risk factors are priorities for clinicians to reduce the incidence of surgical site infections due to its seriousness.

Risk Factors for Revision or Rerupture After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: The rerupture or need for revision after anterior cruciate ligament reconstruction (ACLR) is a serious complication. Preventive strategies that target the early identification of risk factors are important to reduce the incidence of additional surgery. PURPOSE: To perform a systematic review and meta-analysis to investigate risk factors for revision or rerupture after ACLR. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: Literature searches were performed in PubMed, Embase, and Web of Science from database inception to November 2021 and updated in January 2022. Quantitative, original studies reporting potential adjusted risk factors were included. Odds ratios (ORs) were calculated for potential risk factors. RESULTS: A total of 71 studies across 13 countries with a total sample size of 629,120 met the inclusion criteria. Fifteen factors were associated with an increase in the risk of revision or rerupture after ACLR: male sex (OR, 1.27; 95% CI, 1.14-1.41), younger age (OR, 1.07; 95% CI, 1.05-1.08), lower body mass index (BMI) (OR, 1.03; 95% CI, 1.00-1.06), family history (OR, 2.47; 95% CI, 1.50-4.08), White race (OR, 1.32; 95% CI, 1.08-1.60), higher posterolateral tibial slope (OR, 1.15; 95% CI, 1.05-1.26), preoperative high-grade anterior knee laxity (OR, 2.30; 95% CI, 1.46-3.64), higher baseline Marx activity level (OR, 1.07; 95% CI, 1.02-1.13), return to a high activity level/sport (OR, 2.03; 95% CI, 1.15-3.57), an ACLR within less than a year after injury (OR, 2.05; 95% CI, 1.81-2.32), a concomitant medial collateral ligament (MCL) injury (OR, 1.62; 95% CI, 1.31-2.00), an anteromedial portal or transportal technique (OR, 1.36; 95% CI, 1.22-1.51), hamstring tendon (HT) autografts (vs bone-patellar tendon-bone [BPTB] autografts) (OR, 1.60; 95% CI, 1.40-1.82), allografts (OR, 2.63; 95% CI, 1.65-4.19), and smaller graft diameter (OR, 1.21; 95% CI, 1.05-1.38). The other factors failed to show an association with an increased risk of revision or rerupture after ACLR. CONCLUSION: Male sex, younger age, lower BMI, family history, White race, higher posterolateral tibial slope, preoperative high-grade anterior knee laxity, higher baseline Marx activity level, return to a high activity level/sport, an ACLR within less than a year from injury, a concomitant MCL injury, an anteromedial portal or transportal technique, HT autografts (vs BPTB autografts), allografts, and smaller graft diameter may increase the risk of revision or rerupture after ACLR. Raising awareness and implementing effective preventions/interventions for risk factors are priorities for clinical practitioners to reduce the incidence of revision or rerupture after ACLR.

Risk factors for symptomatic rotator cuff tears: a retrospective case-control study.

Background: The incidence and diagnostic rate of rotator cuff tears (RCTs) have increased significantly. The purpose of this study was to investigate and analyze the risk factors for symptomatic RCTs to provide a basis for their prevention and treatment. Methods: We retrospectively analyzed the relevant clinical indicators of 193 randomized clinical trial (RCT) patients and 161 non-RCT patients hospitalized with shoulder pain as the main complaint from January 1, 2017, to August 31, 2021. Univariate analysis and multivariate logistic regression analysis were used to analyze the differences in potential risk factors between the two groups. Results: Univariate analysis revealed that age (p < 0.001), body mass index (BMI) (p = 0.036), hypertension (p < 0.001), coronary heart disease (p = 0.028), history of shoulder trauma (p < 0.001), hyperlipidemia (p = 0.025), type III acromion (p = 0.012) and critical shoulder angle (CSA) (p < 0.001) increased the risk of RCTs. Multivariate logistic regression analysis revealed that age ≥ 60 years (OR = 2.61, 95% CI = 1.23 to 5.12), CSA ≥ 35° (OR = 4.24, 95% CI = 1.60 to 11.22), hypertension (OR = 2.34, 95% CI = 1.33 to 4.11) and history of shoulder trauma (OR = 5.20, 95% CI = 2.87 to 9.45) were independent risk factors for symptomatic RCTs. Conclusion: The results of this study showed that age ≥ 60 years, CSA ≥35°, hypertension and history of shoulder trauma are independent risk factors for symptomatic RCTs and can provide directions for further development of prevention and treatment strategies. Future studies need to clarify the mechanism underlying the association between these risk factors and symptomatic RCTs.

Combination of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) in the treatment of knee osteoarthritis: a meta-analysis of randomised controlled trials.

OBJECTIVES: The purpose of this meta-analysis was to investigate the efficacy and safety of mesenchymal stem cells (MSCs) combined with platelet-rich plasma (PRP) in the treatment of knee osteoarthritis (KOA). DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Patients with KOA. INTERVENTIONS: Use of MSCs+PRP. PRIMARY AND SECONDARY OUTCOMES: Visual Analogue Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Injury and Osteoarthritis Outcome Score (KOOS) and adverse reactions. DATA SOURCES: PubMed, Cochrane Library, Embase and China National Knowledge Infrastructure were searched from inception to 15 July 2021. MEASURES: The OR or weighted mean difference (WMD) of relevant outcome indicators was calculated. Study quality was evaluated using the risk-of-bias assessment tool version 2.0. Heterogeneity among studies was evaluated by calculating I2. If I2＜50%, a fixed-effect model was applied; conversely, if I2 ≥50%, a random-effect model was applied. RESULTS: Six controlled clinical trials with 493 cases were included. The meta-analysis results showed that in terms of the VAS score 3 months after treatment, MSCs+PRP had no significant effect on the reduction of the VAS score in patients with KOA compared with the control (p=0.09), hyaluronic acid (HA) (p=0.15) or PRP alone (p=0.07). MSCs+PRP was more effective in reducing the VAS score at 6 and 12 months after treatment than the control (WMD=-0.55, 95% CI -0.87 to -0.22, p<0.001), HA (WMD=-1.20, 95% CI -2.28 to -0.13, p=0.03) or PRP alone (WMD=-0.54, 95% CI -0.89 to -0.18, p=0.003). Regarding the decrease in the total WOMAC score at 3 and 6 months after treatment, MSCs+PRP showed better clinical efficacy than the control or HA alone (p<0.01). Compared with the control, MSCs+PRP exhibited no significant difference in reducing the total WOMAC score 12 months after treatment (p=0.39). There was no significant difference between MSCs+PRP and the control in terms of improvement of the KOOS 12 months after treatment (p=0.16). Compared with MSCs alone, MSCs+PRP exhibited no significant difference in the incidence of adverse reactions (p=0.22) 12 months after treatment. CONCLUSIONS: Treatment with MSCs+PRP showed good clinical efficacy in improving pain and joint function in patients with KOA. Compared with MSCs alone, there was no significant difference in the incidence of adverse reactions with MSCs+PRP. PROSPERO REGISTRATION NUMBER: CRD 42021275830.

Risk factors for postoperative delirium following total hip or knee arthroplasty: A meta-analysis.

Objectives: The purpose of this study was to identify risk factors for delirium after total joint arthroplasty (TJA) and provide theoretical guidance for reducing the incidence of delirium after TJA. Methods: The protocol for this meta-analysis is registered with PROSPERO (CRD42020170031). We searched PubMed, the Cochrane Library and Embase for observational studies on risk factors for delirium after TJA. Review Manager 5.3 was used to calculate the relative risk (RR) or standard mean difference (SMD) of potential risk factors related to TJA. STATA 14.0 was used for quantitative publication bias evaluation. Results: In total, 25 studies including 3,767,761 patients from 9 countries were included. Old age has been widely recognized as a risk factor for delirium. Our results showed that the main risk factors for delirium after TJA were patient factors (alcohol abuse: RR = 1.63; length of education: SMD = -0.93; and MMSE score: SMD = -0.39), comorbidities (hypertension: RR = 1.26; diabetes mellitus: RR = 1.67; myocardial infarction: RR = 17.75; congestive heart failure: RR = 2.54; dementia: RR = 17.75; renal disease: RR = 2.98; history of stroke: RR = 4.83; and history of mental illness: RR = 2.36), surgical factors (transfusion: RR = 1.53; general anesthesia: RR = 1.10; pre-operative albumin: SMD = -0.38; pre-operative hemoglobin: SMD = -0.29; post-operative hemoglobin: SMD = -0.24; total blood loss: SMD = 0.15; duration of surgery: SMD = 0.29; and duration of hospitalization: SMD = 2.00) and drug factors (benzodiazepine use: RR = 2.14; ACEI use: RR = 1.52; and beta-blocker use: RR = 1.62). Conclusions: Multiple risk factors were associated with delirium after TJA. These results may help doctors predict the occurrence of delirium after surgery and determine the correct treatment. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42020170031.

Influence of type 2 diabetes microangiopathy on bone mineral density and bone metabolism: A meta-analysis.

Background: Diabetic microangiopathy is a type of vascular dysfunction. The effect of type 2 diabetes microangiopathy (DMA) on bone mineral density (BMD) and bone metabolism is still unclear. Objective: A meta-analysis was performed to investigate the effects of microangiopathy on BMD and bone metabolism in type 2 diabetic patients. Methods: We searched the PubMed, Embase, Cochrane Library and CNKI databases to identify observational studies investigating the effects of type 2 diabetes microangiopathy on BMD or bone metabolism. The time limit for the literature retrieval was from the establishment of the database to September 25, 2021. The Newcastle-Ottawa scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) scale were used to evaluate the quality of the studies. RevMan 5.3 software was used for the data analysis. Stata 14.0 was used to quantitatively evaluate the publication bias of the outcome indicators. Results: In total, 12 observational studies were included, including 7 cohort studies, 4 case-control studies and 1 cross-sectional study. In total, 2,500 patients with type 2 diabetes were included. Among them, 1,249 patients had microangiopathy (DMA group), and 1,251 patients did not have microangiopathy (control group). The results of the meta-analysis showed that the BMDs of the femoral neck (SMD = -1.34, 95% CI = -2.22 to -0.45, P = 0.003), lumbar spine (SMD = -0.69, 95% CI = -1.31 to -0.08, P = 0.03) and Ward's triangle (SMD = -2.84, 95% CI = -4.84 to -0.83, P = 0.006) in the DMA group were lower than those in the control group. In the comparison of the bone metabolism indexes, the contents of N-terminal propeptide of type I procollagen (P1NP) (SMD = 0.18, 95% CI = 0.03 to 0.32, P = 0.02), osteocalcin (SMD = 6.97, 95% CI = 3.46 to 10.48, P < 0. 0001), parathyroid hormone (PTH) (SMD = 0.38, 95% CI = 0.03 to 0.73, P = 0.03) and C-telopeptide of type 1 collagen (CTX) (SMD = 0.39, 95% CI = 0.03 to 0.75, P = 0.03) in serum from the DMA group were higher than those in serum from the control group. The serum content of 25-hydroxyvitamin D3 (25(OH)D3) (SMD = -0.63, 95% CI = -1.19 to -0.07, P = 0.03) in the DMA group was lower than that in the control group. There was no significant difference in serum alkaline phosphatase (ALP), calcium or phosphorus between the two groups (P > 0.05). Conclusions: Type 2 diabetes microangiopathy can reduce the lumbar spine, femoral neck and Ward's triangle BMD and has a higher risk of osteoporosis or osteoporosis fractures. The levels of P1NP, PTH, CTX and OC in the serum of patients with type 2 diabetes microangiopathy are higher, and the lower 25(OH)D3 content may be a mechanism by which DMA destroys bone metabolism balance.

Efficacy of Duhuo Jisheng Decoction for Treating Cold-Dampness Obstruction Syndrome-Type Knee Osteoarthritis: A Pooled Analysis.

Aim: The aim of this study is to provide evidence of the effect of Duhuo Jisheng decoction (DHJSD) on knee osteoarthritis (KOA) of the cold-dampness obstruction syndrome type. Methods: We searched PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the Wanfang database, and the China Biology Medicine for randomized controlled trials (RCTs) evaluating DHJSD or DHJSD combined with other conventional therapies (DHJSD group) compared to conventional therapy (control group) for cold-dampness obstruction syndrome-type KOA. We calculated the pooled odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) using fixed- or random-effects models. Results: Eleven RCTs, with a total of 895 patients, were included. The results showed that DHJSD could significantly improve the effective rate (OR = 3.13, 95%CI = 2.07 to 4.72, P < 0.001), reduce both the WOMAC (MD = -12.06, 95%CI = -16.34 to -7.79, P < 0.001) and VAS (MD = -1.02, 95%CI = -1.54 to -0.50, P = 0.0001) scores, and reduce the serum IL-6 (MD = -0.80, 95%CI = -0.90 to -0.69, P < 0.001) and TNF-α (MD = -2.49, 95%CI = -2.77 to -2.21, P < 0.001) levels during the treatment of cold-dampness obstruction syndrome-type KOA. The subgroup analysis showed that compared with glucosamine sulfate (GS) alone, DHJSD combined with GS significantly improved the effective rate (OR = 2.59, 95%CI = 1.19 to 5.65, P = 0.02) and reduced the WOMAC (MD = -13.83, 95%CI = -16.14 to -11.51, P < 0.001) and VAS (MD = -0.91, 95%CI = -1.27 to -0.55, P < 0.001) scores. DHJSD + warm-needle acupuncture (WA) lowered the VAS score more than WA alone. There was no significant difference in the decrease in serum IL-1ß between the DHJSD and control groups. Conclusion: This study shows that DHJSD can improve the clinical efficacy and reduce the VAS and WOMAC scores in the treatment of cold-dampness obstruction syndrome-type KOA. Compared with GS or WA alone, the combined application of DHJSD with GS or WA could better reduce both the VAS and WOMAC scores.

Does anti-nerve growth factor monoclonal antibody treatment have the potential to replace nonsteroidal anti-inflammatory drugs and opioids in treating hip or knee osteoarthritis? A systematic review of randomized controlled trials.

Purpose: Considering the adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids for treating osteoarthritis (OA), development of drugs that are more effective and better tolerated than existing treatments is urgently needed. This systematic review aimed to evaluate the efficacy and safety of anti-nerve growth factor (NGF) monoclonal antibodies vs active comparator therapy, such as NSAIDs and oxycodone, in treating hip or knee OA. Methods: Databases were comprehensively searched for randomized controlled trials (RCTs) published before January 2022. Efficacy and safety outcomes were assessed. Results: Six RCTs that included 4325 patients were identified. Almost all the RCTs indicated that moderate doses of anti-NGF monoclonal antibody treatment significantly improved efficacy outcomes based on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, the WOMAC physical function score and the Patient's Global Assessment compared with those of the active comparator. At least half of the RCTs indicated that the incidence of severe adverse events, withdrawals due to adverse events (AEs) and total joint replacement were not significantly different between anti-NGF monoclonal antibody treatment and active comparator therapy, but the outcomes of some studies may have been limited by a short duration of follow-up. Most RCTs suggested that anti-NGF monoclonal antibody treatment had a lower incidence of gastrointestinal and cardiovascular AEs. However, the majority of RCTs reported a higher incidence of abnormal peripheral sensation with anti-NGF monoclonal antibody treatment. Furthermore, the higher incidence of rapidly progressive osteoarthritis (RPOA) with anti-NGF monoclonal antibody treatment should also not be overlooked, and the identification of patient characteristics that increase the risk of RPOA is critical in further studies. Conclusion: Based on the current research evidence, anti-NGF monoclonal antibodies are not yet a replacement for analgesic drugs such as NSAIDs but might be a new treatment option for hip or knee OA patients who are intolerant or unresponsive to nonopioid or opioid treatment. Notably, however, considering the inconsistency and inconclusive evidence on the safety outcomes of recent studies, more research is needed, and long-term follow-up is required.

The efficacy and safety of Jinwu Gutong capsule in the treatment of knee osteoarthritis: A meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jinwu Gutong (JWGT) capsule is a Chinese patent medicine that is widely used in the treatment of knee osteoarthritis (KOA) and osteoporosis in China and is considered to have the potential for good clinical efficacy. AIM OF THE STUDY: The purpose of this study was to systematically evaluate the clinical efficacy and safety of JWGT in the treatment of KOA. MATERIALS AND METHODS: We searched the China National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, PubMed, Embase and Cochrane Library databases to identify clinical trials that explore the use of JWGT only or JWGT combined with Western drugs (JWGT group) compared with the use of conventional Western drugs (Western drugs group) for the treatment of KOA. The clinical trials, that were retrieved from each database from the inception of the database to December 2021, were screened. We used the risk of bias assessment tool recommended by Cochrane to evaluate the quality of the included literature and RevMan 5.3 software for data analysis. RESULTS: A total of 17 clinical randomized controlled trials (RCTs) were included in this study, with a total of 1930 participants, including 1015 people in the experimental group and 915 people in the control group. The results of the meta-analysis showed that the JWGT group exhibited better efficacy than the Western drug group with respect to WOMAC score (WMD = -6.25, 95% CI = -8.09 to -4.41, P < 0.001), VAS score (WMD = -1.36, 95% CI = -2.17 to -0.55, P = 0.001), KSS score (WMD = 23.01, 95% CI = 21.42 to 24.59, P < 0.001), IL-6 (SMD = -3.30, 95% CI = -4.84 to -1.76, P < 0.001), TNF-α (SMD = -1.70, 95% CI = -2.02 to -1.38, P < 0.001). The effective rate (OR = 2.56, 95% CI = 1.83 to 3.57, P < 0.001) and incidence of adverse reactions was significantly lower in the JWGT group than in the control group (OR = 0.13, 95% CI = 0.07 to 0.21, P < 0.001). Subgroup analysis showed that JWGT + NSAIDs had more advantages in regard to efficacy (OR = 2.05, 95% CI = 1.35 to 3.12, P < 0.001), and reducing adverse reactions (OR = 0.10, 95% CI = 0.06 to 0.18, P < 0.001), VAS score (WMD = -1.00, 95% CI = -1.93 to -0.07, P = 0.04), KSS score (WMD = 17.39, 95% CI = 15.39 to 19.39, P < 0.001), WOMAC score (WMD = -2.84, 95% CI = -10.75 to 5.08, P < 0.001), IL-6 (SMD = -1.42, 95% CI = -2.08 to -0.75, P < 0.001) and TNF-α (SMD = -1.68, 95% CI = -1.93 to -1.43, P < 0.001) than NSAIDs alone. Compared with hyaluronic acid (HA) alone, JWGT + HA had better clinical efficacy (OR = 3.08, 95% CI = 1.48 to 6.40, P < 0.001). Compared with glucosamine (GS) alone, JWGT + GS significantly reduced the Lequesne index score (WMD = -0.53, 95% CI = -0.85 to -0.21, P = 0.001) and the serum TNF-α level (SMD = -1.68, 95% CI = -1.93 to -1.43, P < 0.001), but it had no significant advantage in reducing the serum IL-6 level (SMD = -4.53, 95% CI = -10.13 to 1.07, P = 0.11). CONCLUSION: JWGT is considered effective and safe in the treatment of KOA and is worthy of clinical application. In addition, the application of JWGT combined with NSAIDs, HA or GS can significantly improve the clinical efficacy of the latter agents in KOA treatment.

Comparisons of the Efficacy and Safety of Total Knee Arthroplasty by Different Surgical Approaches: A Systematic Review and Network Meta-analysis.

The purpose of this network meta-analysis was to investigate the efficacy and safety of total knee arthroplasty (TKA) considering seven different surgical approaches. Four databases (PubMed, Cochrane Library, EMBASE, Web of Science) were searched for clinical randomized controlled trials (RCTs) involving TKA with different surgical approaches. STATA 14.0 was used to construct network maps and publication bias graphs and conduct inconsistency tests, network meta-analyses, and surface under the cumulative ranking (SUCRA) calculations. A total of 51 RCTs involving 4061 patients and 4179 knees from 18 countries were included. Among the seven surgical approaches, the midvastus approach (MV) was the top choice to reduce tourniquet use time, the subvastus approach (SV) had the shortest operation time, the mini-midvastus approach (Mini-SV) was associated with the least amount of time to achieve straight leg raise (SLR) after surgery, the mini-medial parapatellar approach (Mini-MP) reduced postoperative pain effects, and the medial parapatellar approach (MP) was the best approach to improve range of motion (ROM). Excluding the quadriceps-sparing approach (QS), which was not compared, the use of the mini-midvastus (Mini-MV) may shorten the hospital stay. There were no significant differences in blood loss, postoperative complications, American Knee Society Score (AKSS) objective, or AKSS functional between the seven surgical approaches (P > 0.05).

Based on minimal clinically important difference values, a moderate dose of tanezumab may be a better option for treating hip or knee osteoarthritis: a meta-analysis of randomized controlled trials.

BACKGROUND: Tanezumab is a nerve growth factor monoclonal antibody that may regulate pain in hip or knee osteoarthritis (OA). This meta-analysis was performed to evaluate the efficacy and safety of low and moderate doses of tanezumab in treating hip or knee OA. METHODS: PubMed, EMBASE, the Cochrane Library, and Web of Science were comprehensively searched for clinical trials published before 1 May 2021. Patients were assessed via efficacy and safety outcomes. RESULTS: Twelve randomized controlled trials including 6022 patients were identified. Both low and moderate doses of tanezumab significantly improved efficacy outcomes. However, only the point estimates (mean difference, MD) of moderate-dose tanezumab significantly exceeded the minimal clinically important differences (MCIDs). There were no significant differences in the incidence of treatment-related adverse events (AEs), withdrawals due to AEs, serious AEs, and total joint replacement between the tanezumab and placebo groups, whereas the incidence of AEs was higher in the tanezumab group (relative risk, RR = 1.10; 95% confidence interval, 95% CI = 1.04-1.17). The incidence of rapidly progressive OA was significantly higher in the combined low- and moderate-dose tanezumab groups than in the placebo group (RR = 5.01; 95% CI = 1.17-21.33). Furthermore, both low and moderate doses of tanezumab significantly increased the incidence of abnormal peripheral sensation (RR = 1.99, 95% CI = 1.21-3.28; RR = 2.64, 95% CI = 1.91-3.67, respectively). Compared with nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, tanezumab showed significantly improved efficacy outcomes (p < 0.05). However, the point estimates (MD) of tanezumab were not greater than the MCID. Pooled analysis showed no significant differences between tanezumab and NSAIDs and opioids in safety outcomes (p > 0.05). CONCLUSION: Tanezumab is efficacious in patients with hip or knee OA. Tanezumab is relatively well tolerated and safe but increases the incidence of AEs and reversible abnormal peripheral sensation. Additional studies on the occurrence of rapidly progressive OA are needed. A moderate dose of tanezumab may maximize the benefits for hip or knee OA.

What Factors Are Associated with Symptomatic Rotator Cuff Tears: A Meta-analysis.

BACKGROUND: Rotator cuff tears are common. A previous systematic review reported on factors associated with rotator cuff tears; however, it included relatively few studies and few variables, and in addition, it had considerable heterogeneity. To identify the factors associated with symptomatic rotator cuff tears and to help guide clinicians to potentially modifiable factors, we felt a broader and more inclusive meta-analysis would be useful. QUESTIONS/PURPOSES: In this systematic review and meta-analysis, we asked what (1) demographic, (2) disease, and (3) imaging factors are associated with symptomatic rotator cuff tears? METHODS: PubMed, Embase, and Web of Science were searched, and the search period were from the inception of each database through February 2021. The keywords included "risk factor," "rotator cuff injury," "rotator cuff tears," and "rotator cuff tendinitis." All comparative studies on symptomatic rotator cuff tears were included. We considered that the diagnosis of rotator cuff tear could be made by any imaging tool (MRI or ultrasound). We considered either partial- or full-thickness tears to be a rotator cuff tear. No language restrictions were applied. Twenty-six articles from 14 countries involving 9809 individuals, consisting of 3164 patients and 6645 controls, were included. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality (AHRQ) scale were used to evaluate the risk of bias of the included studies, and the highest scores were 9 and 11, respectively. The Newcastle-Ottawa Scale was used for retrospective comparative studies, and the AHRQ was used to evaluate prospective comparative studies. The eight retrospective comparative studies we included were scored from 4 to 9. The quality score of the 18 prospective comparative studies ranged from 6 to 9. Publication bias was explored using the Egger test. Heterogeneity was estimated using the I2 value. If there was no heterogeneity (I2 ≤ 50%), a fixed-effects model was used to determine the overall effect size; if there was heterogeneity (I2 > 50%), a random-effects model was used to merge the effect values. A meta-analysis was performed with RevMan 5.3, and the risk ratio (RR) and weighted mean difference of related factors were calculated. RESULTS: Our meta-analysis identified the following demographic factors associated with an increased risk of rotator cuff tears: older age (mean difference 3.1 [95% CI 1.4 to 4.8]; p < 0.001), greater BMI (mean difference 0.77 [95% CI 0.37 to 1.17]; p < 0.001), smoking (RR 1.32 [95% CI 1.17 to 1.49]; p < 0.001), dominant arm (RR 1.15 [95% CI 1.06 to 1.24]; p < 0.001), greater height (mean difference 0.9 [95% CI 0.4 to 1.4]; p < 0.001), and heavier weight (mean difference 2.24 [95% CI 0.82 to 3.66]; p = 0.002). Regarding disease factors, we found that traumatic events (RR 1.91 [95% CI 1.40 to 2.54]; p < 0.001) and hypertension (RR 1.50 [95% CI 1.32 to 1.70]; p < 0.001) were associated with symptomatic rotator cuff tears. Regarding imaging factors, we found that the following three factors were associated with symptomatic rotator cuff tears: greater acromion index (mean difference 0.11 [95% CI 0.06 to 0.16]; p < 0.001), greater critical shoulder angle (mean difference 1.9 [95% CI 1.5 to 2.3]; p < 0.001), and smaller glenoid version angle (mean difference -1.3 [95% CI -1.9 to -0.8]; p < 0.001). We found no association between the patient's sex or the presence or absence of thyroid disease and the likelihood of a rotator cuff tear being present. CONCLUSION: This study identified several factors associated with symptomatic rotator cuff tears, including blood glucose, blood pressure, weight, and smoking. Clinicians may seek to modify these factors, possibly in patients with symptomatic rotator cuff tears, but also in symptomatic patients who have not yet been diagnosed with rotator cuff tears because there would be no harm or risk associated with modifying any of the factors we identified. Future research should further study whether addressing these factors can delay the progression and size of rotator cuff tears.Level of Evidence Level III, prognostic study.