Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss: findings from the Shanghai Osteoarthritis Cohort.

OBJECTIVE: Obesity is a risk factor for knee osteoarthritis (KOA) development and progression. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity. However, whether KOA patients can benefit from GLP-1RA therapies has not been sufficiently investigated, especially in the long term. METHODS: The Shanghai Osteoarthritis Cohort study is a prospective, observational, multicentre study of >40 000 adults with clinically diagnosed osteoarthritis aged >45 years in Shanghai. We identified all KOA participants with comorbid T2DM enrolled from 1 January 2011 to 1 January 2017. Primary outcome was incidence of knee surgery after enrolment. Secondary outcomes included pain-relieving medication use, number of intra-articular therapies, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and medial femorotibial joint cartilage thickness. To evaluate the effects of GLP-1RA, we performed before-and-after comparison and comparison with participants who had no GLP-1RA exposure. RESULTS: For an intergroup comparison (non-GLP-1RA vs GLP-1RA), more weight loss (adjusted mean difference in weight change from baseline -7.29 kg (95% CI -8.07 to -6.50 kg), p<0.001) and lower incidence of knee surgery (93/1574 (5.9%) vs 4/233 (1.7%), adjusted p=0.014) were observed in the GLP-1RA group. Statistically significant differences in mean change from baseline for the WOMAC total and pain subscale scores were observed (adjusted mean difference in WOMAC total score -1.46 (95% CI -2.84 to -0.08), p=0.038; adjusted mean difference in WOMAC pain subscore -3.37 (95% CI -5.79 to -0.94), p=0.007). Cartilage-loss velocity of the medial femorotibial joint was significantly lower in the GLP-1RA group postadjustment for baseline characteristics (adjusted mean difference -0.02 mm (95% CI -0.03 to -0.002 mm), p=0.004). For the before-and-after comparison within the GLP-1RA group, we observed a significant decrease of symptom-relieving medication consumption and cartilage loss velocity of medial femorotibial joint (after-treatment vs before-treatment: -0.03±0.05 vs -0.05±0.07 mm/year, p<0.001). The association between GLP-1RA exposure and decreased incidence of knee surgery was mediated by weight reduction (mediation proportion: 32.1%), instead of glycaemic control (too small to calculate). CONCLUSION: With sufficient treatment duration, GLP-1RA therapies might be disease-modifying for KOA patients with comorbid T2DM, possibly mediated by weight loss. Further investigation is needed to elucidate effects of GLP-1RA on disease process, joint structure and patient-reported outcomes of osteoarthritis.

Computerised tomography features of giant cell tumour of the knee are associated with local recurrence after extended curettage.

BACKGROUND: Extended curettage has increasingly become the preferred treatment for giant cell tumour of bone (GCTB), but the high recurrence rate after curettage poses a major challenge for orthopaedic surgeons. Computed tomography (CT) is valuable in the evaluation of GCTB. Our aim was to identify specific features of GCTB around the knee in pre-operative CT images that might have prognostic value for local recurrence. METHODS: We retrospectively analyzed data from 124 patients with primary GCTB around the knee who underwent extended curettage from 2010 through 2019. We collected demographic, clinical, and therapeutic data along with several CT-derived tumour characteristics. CT-derived tumor characteristics included tumour size, the distance between the tumour edge and articular surface (DTA), and destruction of posterior cortical bone (DPC). Akaike information criterion (AIC) was used to select which variables to enter into multivariate logistic regression models and to determine significant factors affecting recurrence. RESULTS: The total recurrence rate was 21.0% (26/124), and the average follow-up time was 69.5 ± 31.2 months (24-127 months). Age, DTA (< 2 mm), and DPC were significantly related to recurrence, as determined by multivariate logistic regression. The C-index of the final model was 0.79 (95% CI: 0.71 to 0.88), representing a good model for predicting recurrence. CONCLUSION: Identifying certain features of GCTB around the knee on CT has prognostic value for patients treated with extended curettage. A three-factor model predicts tumour recurrence well after extended curettage.

Preoperative CT for prediction of local recurrence after curettage of giant cell tumor of bone.

•Preoperative CT images of GCTBs have value in prognostic prediction.•Certain features of GCTBs on CT images are related to local recurrence.•Our models' predictions for GCTB patients accepting extensive curettage are good.

Alpha-(1,6)-fucosyltransferase (FUT8) affects the survival strategy of osteosarcoma by remodeling TNF/NF-κB2 signaling.

Glycosylation is an important modification of membrane proteins that results in functional changes in many cellular activities, from cell-cell recognition to regulatory signaling. Fucosyltransferase 8 (FUT8) is the sole enzyme responsible for core fucosylation, and aberrant fucosylation by dysregulated expression of fucosyltransferases is responsible for the growth of various types of carcinomas. However, the function of FUT8 in the progress of osteosarcoma (OS) has not been reported. In this study, we found that FUT8 is expressed at lower levels in patients with OS and in human OS cell lines such as MNNG/HOS, U2OS, and 143B, suggesting that attenuated expression of FUT8 is involved in the growth and progression of OS. Mechanistically, FUT8 affects the survival strategy of OS by modifying core-fucosylation levels of TNF receptors (TNFRs). Lower fucosylation of TNFRs activates the non-canonical NF-κB signaling pathway, and in turn, decreases mitochondria-dependent apoptosis in OS cells. Together, our results point to FUT8 being a negative regulator of OS that enhances OS-cell apoptosis and suggests a novel therapeutic strategy for treating OS.

Intestinal methicillin-resistant Staphylococcus aureus causes prosthetic infection via 'Trojan Horse' mechanism: Evidence from a rat model.

AIMS: Methicillin-resistant Staphylococcus aureus (MRSA) can cause wound infections via a 'Trojan Horse' mechanism, in which neutrophils engulf intestinal MRSA and travel to the wound, releasing MRSA after apoptosis. The possible role of intestinal MRSA in prosthetic joint infection (PJI) is unknown. METHODS: Rats underwent intestinal colonization with green fluorescent protein (GFP)-tagged MRSA by gavage and an intra-articular wire was then surgically implanted. After ten days, the presence of PJI was determined by bacterial cultures of the distal femur, joint capsule, and implant. We excluded several other possibilities for PJI development. Intraoperative contamination was excluded by culturing the specimen obtained from surgical site. Extracellular bacteraemia-associated PJI was excluded by comparing with the infection rate after intravenous injection of MRSA or MRSA-carrying neutrophils. To further support this theory, we tested the efficacy of prophylactic membrane-permeable and non-membrane-permeable antibiotics in this model. RESULTS: After undergoing knee surgery eight or 72 hours after colonization, five out of 20 rats (25.0%) and two out of 20 rats (10.0%) developed PJI, respectively. Strikingly, 11 out of 20 rats (55.0%) developed PJI after intravenous injection of MRSA-carrying neutrophils that were isolated from rats with intestinal MRSA colonization. None of the rats receiving intravenous injections of MRSA developed PJI. These results suggest that intestinal MRSA carried by neutrophils could cause PJI in our rat model. Ten out of 20 (50.0%) rats treated with non-membrane-permeable gentamicin developed PJI, whereas only one out of 20 (5.0%) rats treated with membrane-permeable linezolid developed PJI. CONCLUSION: Neutrophils as carriers of intestinal MRSA may play an important role in PJI development.Cite this article: Bone Joint Res. 2020;9(4):152-161.

Pre-injury level of anxiety is associated with the rate of digit replant failure: A prospective cohort study.

BACKGROUND: Previous studies have demonstrated that age, smoking, Tamai's level of amputation, causes of injury and ischemia time were associated with the success rate of digit replantation. The primary objective of this study is to investigate whether mental status including anxiety and depression is associated with the rate of digit replant failure. METHODS: This study included 134 digits from 102 patients who received digital replantation after complete amputation from 1 September 2013 to 1 September 2015. The Zung self-rating anxiety scale (SAS) and the Zung self-rating depression scale (SDS) were used to assess the pre-injury level of anxiety and depression for each patient. All participants were followed up for at least 1 month. Failure was defined as necrosis of replanted finger which required revision amputation or flap cover of the skeleton. RESULTS: Multivariate logistic regression analysis showed that increased level of pre-injury anxiety was an independent risk factor correlated with success rate (odds ratios [OR] = 7.69, 95% confidence interval [CI]: 1.93-30.30) in this series. The relative risk of anxiety group was 4.48 (95% CI: 1.38-14.49) compared to normal group. Digits with double arterial anastomosis in anxiety patients showed a higher survival rate while the number of veins repaired showed no significant effect on survival rate. CONCLUSIONS: Increased level of pre-injury anxiety was an independent risk factors for digit replantation failure. Double arterial anastomosis increased the success rate of replanted digits in anxiety patients.