Aim. Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios. Method. Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration. Results. Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 µg/mL) in calcaneal cancellous bone and subcutaneous tissue throughout the 90 min tourniquet duration in Group A and B. Cefuroxime administration at tourniquet release (Group C) resulted in concentrations above 4 µg/mL for a minimum of 3.5 hours in the tissues on the tourniquet side. There were no significant differences in the T>MIC (4 µg/mL) in subcutaneous tissue or calcaneal cancellous bone between the three groups. However, Group A tended toward shorter T>MIC in tourniquet calcaneal cancellous bone compared to Group C (p=0.08). Conclusions. Administration of cefuroxime (1.5 g) in the 15–45 min window prior to tourniquet inflation resulted in sufficient calcaneal cancellous bone and subcutaneous tissue concentrations throughout the 90 min tourniquet application. If the target is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at tourniquet release

MSCs (mesenchymal stem cells) are bone marrow-derived cells capable of replication and differentiation in-vitro into several tissues including bone, cartilage, stroma, fat, muscle and tendon. MSCs can be isolated by relatively simple procedures and then expanded without losing the ability to differentiate into multiple lineages. As such, these cells have immense clinical potential in regenerative medicine and in orthopaedics for repair or replacement of damaged tissues. In this work we investigated the interaction between magnetic carbon nanotubes (CNTs) and MSCs and their ability to guide these cells injected intravenously in living mice by using an external magnetic field. CNTs did not affect cell viability and their ability to differentiate. Both the CNTs and the magnetic field did not alter cell growth rate, phenotype and cytoskeletal conformation. CNTs, when exposed to magnetic fields, are able to shepherd MSCs towards the magnetic source in vitro. Moreover, the application of a magnetic field alters the biodistribution of CNT-labelled MSCs after intravenous injection into rats. We demonstrated that CNTs hold the potential for use as nano-devices to improve therapeutic protocols for transplantation and homing of stem cells in vivo. This could pave the way for the development of new strategies for manipulation/guidance of MSCs in regenerative medicine and cell transplantation for the treatment of many orthopaedic diseases

We aimed to measure cerebral microemboli load during total hip [THA] and knee arthroplasty (TKA) using transcranial Doppler ultrasound (TCD) and to investigate whether cerebral embolic load influences neuropsychiatric outcome. The timing of the microemboli was also related to certain surgical activities to determine if a specific relationship exists and the presence of a patent foramen ovale was investigated. Patients undergoing primary THA and TKA underwent a battery of ten neuropsychiatric tests pre-operatively and at 6 weeks and 6 months post-operatively. Microembolic load was recorded using TCD onto VHS tape for subsequent analysis. Patent foramen ovale detection was performed using bolus intravenous injection of agitated saline followed by valsalva manoeuvre. The timing of specific surgical steps was recorded for each operation and embolic load calculated for that period. All patients were assessed for quality of life and orthopaedic outcome measures. Results. 45 THA patients and 50 TKA patients were studied. Cerebral microembolisation occurred in 35% of all patients (10 THA patients and 19 TKA patients). Mean microembolic load was 2.8 per patient for THA and 3.76 per patient for TKA patients. PFO was detected in 29 patients overall. Insertion of the femoral component and deflation of the tourniquet were associated with a larger microembolic loads. Neuropsychiatric outcome was not affected by the low embolic loads. Quality of life and Orthopaedic outcome at 6 months was good. Conclusion. Cerebral microembolisation occurs in a significant proportion of patients during total hip and knee arthroplasty. The presence of a patent foramen ovale does not appear to influence the incidence of microembolisation or load. Specific surgical activities are associated with generating greater embolic loads and methods of avoiding these emboli such as venting the femur may minimise complications and optimise outcomes. Neuropsychiatric outcomes do not seem to be affected by microembolisation of the brain during total joint arthroplasty

A prospective, randomized, double-blind study was done on 50 patients undergoing primary cementless total hip arthroplasty to determine the effect of tranexamic acid on intra- and postoperative blood losses and on the transfusions requirements. 50 patients were randomized to tranexamic acid (15 mg/kg) given as a bolus intravenous injection or placebo (normal saline) given intravenously, 15 minutes before the incision. The intraoperative and postoperative blood loss (at removal of the drain 24 hours after the operation) and the number of blood transfusions required were recorded. The patients were screened for deep venous thrombosis with bilateral compression Ultrasonography using Colour Doppler imaging on the tenth postoperative day. The Hemoglobin level was measured preoperatively and on the 3rd postoperative day. The D-dimer levels were measured preoperatively and 24 hrs postoperatively. Patients receiving tranexamic acid had a mean intraoperative blood loss of 410 ml (range, 300–510 ml) versus 615 ml (range, 515–750ml) (p value<0.05) in patients receiving placebo, a postoperative blood loss of 210 ml(range, 150–325ml) versus 490 ml(range, 370–540ml) (p value<0.05), and a total need for 8 blood transfusions versus 30. Only 6 out 25 patients in tranexamic acid group required blood transfusion whereas 18 out of 25 patients in the placebo group required transfusion. In the group receiving placebo the mean fall in hemoglobin was 2.9g/dl (range, 2.5–3.2) and in the group treated with tranexamic acid 1.6 g/dl (1.3–2) (p<0.05). At 24 hrs postoperatively, mean plasma D-dimer concentration in the Tranexamic group was half of that in the control group. No patient in either group had any evidence of deep vein thrombosis on bilateral compression Ultrasonography using Colour Doppler imaging done on the tenth postoperative day. Tranexamic acid 15 mg/kg given as a single preoperative bolus dose reduces peroperative and postoperative and total blood loss, and transfusion requirements in primary cementless total hip replacement surgery without any increased risk of thrombus formation

A prospective, randomized, double-blind study was done on 50 patients undergoing primary cementless total hip arthroplasty to determine the effect of tranexamic acid on intra- and postoperative blood losses and on the transfusions requirements. 50 patients were randomized to tranexamic acid (15 mg/kg) given as a bolus intravenous injection or placebo (normal saline) given intravenously, 15 minutes before the incision. The intraoperative and postoperative blood loss (at removal of the drain 24 hours after the operation) and the number of blood transfusions required were recorded. The patients were screened for deep venous thrombosis with bilateral compression Ultrasonography using Colour Doppler imaging on the tenth postoperative day. The Haemoglobin level was measured preoperatively and on the 3rd postoperative day. The D-dimer levels were measured preoperatively and 24 hrs postoperatively. Patients receiving tranexamic acid had a mean intraoperative blood loss of 410 ml (range, 300-510 ml) versus 615 ml (range, 515-750ml) (p value<0.05) in patients receiving placebo, a postoperative blood loss of 210 ml(range, 150-325ml) versus 490 ml(range,370-540ml) (p value<0.05), and a total need for 8 blood transfusions versus 30. Only 6 out 25 patients in tranexamic acid group required blood transfusion whereas 18 out of 25 patients in the placebo group required transfusion. In the group receiving placebo the mean fall in haemoglobin was 2.9g/dl (range, 2.5-3.2) and in the group treated with tranexamic acid 1.6 g/dl (1.3-2) (p<0.05). At 24 hrs postoperatively, mean plasma D-dimer concentration in the Tranexamic group was half of that in the control group. No patient in either group had any evidence of deep vein thrombosis on bilateral compression Ultrasonography using Colour Doppler imaging done on the tenth postoperative day. Tranexamic acid 15 mg/kg given as a single preoperative bolus dose reduces peroperative and postoperative and total blood loss, and transfusion requirements in primary cementless total hip replacement surgery without any increased risk of thrombus formation

Purpose. Maintenance of vertebral mechanical stability is of paramount importance to prevent pathologic fractures and resultant neurologic compromise in individuals with spinal metastases. Current non-surgical treatments for vertebral metastases (i.e. chemotherapy, bisphophonates (BP) and radiation) yield variable responses in the tumour and surrounding bone. Photodynamic therapy (PDT) is a novel, minimally-invasive technology that utilizes a drug activated by light at a specific non-thermal wavelength to locally destroy tumour cells. Previously, we observed that PDT can ablate cancer cells within bone and yield short-term (1-week) improvements in vertebral architecture and biomechanical strength, particularly when combined with BP therapy. This study aims to evaluate the effects of PDT in vertebral bone over a longer (6-week) time period, alone and combined with previous BP treatment, to determine if improvements in skeletal architecture and strength are maintained. Method. Fourty healthy rnu/rnu rats were randomly assigned to four treatment groups: (i) untreated control, (ii) BP only, (iii) PDT only and (iv) PDT following BP. BP treatments were administered on day 0 via subcutaneous injection of zoledronic acid. PDT was administered on day 7 via an intravenous injection of BPD-MA photosensitizer. A flat-cut optical fiber was inserted percutaneously adjacent to lumbar vertebra L2. After a 15-minute drug-light interval, 75J of light energy was delivered from a 690nm laser. Six weeks later, animals were euthanized. Structural properties of excised L2 vertebral bodies were quantified through semi-automated analysis of micro-CT images. In of the specimens, mechanical properties were evaluated by loading the L2 vertebral body to failure in axial compression. The remaining L2 vertebrae were analyzed for morphology, osteoid formation and osteoclast activity using histological methods. Results. Combined PDT+BP treatment yielded the largest increases in bone volume fraction (31%), trabecular thickness (45%) and vBMD (37%) and decreases in trabecular number (14%) and separation (26%) compared to untreated controls (n=10, all p<0.05). The cortical shell mass fraction was significantly lower than that of controls (24%) indicating increases in bone structure were primarily due to trabecular changes. Mechanically, PDT+BP treatment demonstrated a trend towards an increase in ultimate force compared to controls (n=5, p=0.176). BP-only and PDT-only treatments demonstrated similar trends to the combined treatment, but with a lower magnitude of effect. Qualitatively, histological analysis suggested more osteoid formation in groups receiving PDT, and a higher proportion of bone in BP-treated groups. Conclusion. PDT has a sustained positive effect on the mechanical and structural integrity of bone, particularly in combination with BP treatment. By ablating tumour tissue and strengthening bone, combined PDT+BP treatment presents as an attractive adjuvant minimally-invasive therapy for spinal metastasis