Aims. To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMDSV) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ). Methods. In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDSV on alternate days for four weeks. Chondrocytes were also treated with PPARγ inhibitor, PPARγ inhibitor+ UTMDSV, and UTMDSV. The cholesterol efflux rate and triglyceride levels were measured using an assay kit and oil red O staining, respectively. In vivo, the OA rabbits were treated with a single intra-articular injection of UTMD, SV, and UTMDSV every seven days for four weeks. Cartilage histopathology was assessed by safranin-O staining and the Mankin score. Total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) in rabbit knee synovial fluid were detected by enzyme-marker assay. Aggrecan, collagen II, and PPARγ expression levels were analyzed by Western blotting (WB). Results. In vitro, UTMDSV significantly increased the cholesterol efflux rate and aggrecan, collagen II, and PPARγ levels in OA chondrocytes; these effects were blocked by the PPARγ inhibitor. In vivo, UTMD. SV. significantly increased aggrecan, collagen II, PPARγ, and HDL-C levels, while TC levels and Mankin scores were decreased compared with the UTMD, SV, OA, and control groups. Conclusion. UTMDSV promotes cartilage extracellular matrix synthesis by modulating the PPARγ-mediated cholesterol efflux pathway in OA rabbits. Cite this article: Bone Joint Res 2021;10(10):693–703

Aims. This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs). Methods. A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were treated with different groups. Biofilm biomass differences were determined by staining. Thickness and bacterial viability were observed with confocal laser scanning microscope (CLSM). Colony counts were determined by plate-counting. Scanning electron microscopy (SEM) observed bacterial morphology. Results. The Vm-MBs and Mp-MBs met the experimental requirements. The biofilm biomass in the Vm, Vm-MBs, UTMD, and Vm-MBs + UTMD groups was significantly lower than in the control group. MRSA and E. coli biofilms were most notably damaged in the Vm-MBs + UTMD group and Mp-MBs + UTMD group, respectively, with mean 21.55% (SD 0.08) and 19.73% (SD 1.25) remaining in the biofilm biomass. Vm-MBs + UTMD significantly reduced biofilm thickness and bacterial viability (p = 0.005 and p < 0.0001, respectively). Mp-MBs + UTMD could significantly decrease biofilm thickness and bacterial viability (allp < 0.001). Plate-counting method showed that the numbers of MRSA and E. coli bacterial colonies were significantly lower in the Vm-MBs + UTMD group and the Mp, Mp-MBs, UTMD, Mp-MBs + UTMD groups compared to the control group (p = 0.031). SEM showed that the morphology and structure of MRSA and E. coli were significantly damaged in the Vm-MBs + UTMD and Mp-MBs + UTMD groups. Conclusion. Vm-MBs or Mp-MBs combined with UTMD can effectively disrupt biofilms and protectively release antibiotics under ultrasound mediation, significantly reducing bacterial viability and improving the bactericidal effect of antibiotics. Cite this article: Bone Joint Res 2024;13(9):441–451

Background: Confusion occurs in up to 60% of patients following neck of femur fracture, delaying hospital discharge. We investigated venous – arterial circulation shunts (v-aCS) and the influence of cerebral embolism before and during surgery on subsequent cognitive function. Methods: Cerebral emboli were counted in 16 patients with an inter-trochanteric or Garden III/IV fracture by transcranial Doppler (TCD) monitoring over 1 hour pre-operatively and intra-operatively. A v-aCS was diagnosed when 1 or more microbubbles were detected in the middle cerebral artery by TCD following intravenous injection of a microbubble emulsion. Cognitive function was investigated by a battery of computerised tests preoperatively and at 5 days postoperatively. Results: Cerebral emboli were detected in 9 of 16 patients preoperatively (median 2, range 1–23) and in 10 patients during surgery (median 10, range 4 – 617). A v-aCS was associated with preoperative emboli in 9 patients (p=0.036, Fisher’s Exact) and intraoperative emboli in 10 patients (p=0.011, Fisher’s Exact). Cognitive function deteriorated following surgery only in patients with emboli, with the median (range) overall reaction times increasing from 3220ms (1926–5868) to 7493ms (4690–15992) [p=0.008]. The overall accuracy deteriorated from 2.57 to 2.37 (NS). Conclusion: Cerebral embolism is common following femoral neck fracture in patients with a v-aCS and was associated with a deterioration in cognitive function

Background: Cerebral emboli may be detected by transcranial Doppler (TCD) in patients undergoing hip arthroplasty. Venous – arterial circulation shunts (v-aCS), cerebral embolism and postoperative organ dysfunction were investigated in elective hip arthroplasty. Methods: TCD was used to identify v-aCS in (i) elective hip arthroplasty (n=45), (ii) abdominal aortic aneurysm surgery (AAA) (n=20) and (iii) transurethral resection of prostate (TURP) (n=10). A v-aCS was diagnosed when 1 or more microbubbles were detected in the middle cerebral artery by TCD following intravenous injection of a microbubble emulsion. TCD was also used to monitor for intraoperative cerebral emboli (ICE). Cognitive function was measured by a battery of computerised tests before and 5 days after surgery. Troponin T, AST, ALP, Bilirubin, Creatinine, Urea and Creatinine clearance were measured pre-operatively and 24 and 48 hours post-operatively. Results: Cerebral embolism occurred in 26 of 45 patients during hip arthroplasty (median 4, range 1 – 368) but not during AAA or TURP surgery. Cerebral embolism only occurred in patients with a v-aCS (p< 0.001) and was strongly associated with the size of the v-aCS (rs=0.8, p< 0.001). The number of ICE had no influence on Troponin T, renal function, liver function or cognitive function. Conclusion: Cerebral embolism is common in patients with a v-aCS during hip arthroplasty. There was no evidence of cerebral or multi-organ damage due to paradoxical embolism

Fat embolism occurs following fractures of a long bone or arthroplasty. We investigated whether paradoxical embolisation through a venous-to-arterial circulation shunt (v-a) could lead to cerebral embolisation during elective hip or knee arthroplasty. Transcranial Doppler ultrasound (TCD), following the intravenous injection of microbubble contrast, identified the presence of a shunt in 41 patients undergoing hip (n=20) or knee (n=21) arthroplasty. Intra-operative cerebral embolism was detected during continuous TCD monitoring. Of the 41 patients, 34 had a v-a shunt of whom 18 had an embolism and embolism only occurred in patients with a shunt (p = 0.012). Spontaneous and larger shunts were associated with a greater number of emboli (r. s. = 0.67 and r. s. = 0.71 respectively, p < 0.01). Observations in two patients with large spontaneous shunts revealed 368 and 203 emboli and unexplained post-operative confusion and pancreatitis. Paradoxical cerebral embolisation only occurred in patients with a shunt and may explain both postoperative confusion and fat embolism syndrome following surgery

Objectives

The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management.

Objective

Dunkin Hartley guinea pigs, a commonly used animal model of osteoarthritis, were used to determine if high frequency ultrasound can ensure intra-articular injections are accurately positioned in the knee joint.