Aims. Trained immunity confers non-specific protection against various types of infectious diseases, including bone and joint infection. Platelets are active participants in the immune response to pathogens and foreign substances, but their role in trained immunity remains elusive. Methods. We first trained the innate immune system of C57BL/6 mice via intravenous injection of two toll-like receptor agonists (zymosan and lipopolysaccharide). Two, four, and eight weeks later, we isolated platelets from immunity-trained and control mice, and then assessed whether immunity training altered platelet releasate. To better understand the role of immunity-trained platelets in bone and joint infection development, we transfused platelets from immunity-trained mice into naïve mice, and then challenged the recipient mice with Staphylococcus aureus or Escherichia coli. Results. After immunity training, the levels of pro-inflammatory cytokines (tumour necrosis factor alpha (TNF-α), interleukin (IL)-17A) and chemokines (CCL5, CXCL4, CXCL5, CXCL7, CXCL12) increased significantly in platelet releasate, while the levels of anti-inflammatory cytokines (IL-4, IL-13) decreased. Other platelet-secreted factors (e.g. platelet-derived growth factor (PDGF)-AA, PDGF-AB, PDGF-BB, cathepsin D, serotonin, and histamine) were statistically indistinguishable between the two groups. Transfusion of platelets from trained mice into naïve mice reduced infection risk and bacterial burden after local or systemic challenge with either S. aureus or E. coli. Conclusion. Immunity training altered platelet releasate by increasing the levels of inflammatory cytokines/chemokines and decreasing the levels of anti-inflammatory cytokines. Transfusion of platelets from immunity-trained mice conferred protection against bone and joint infection, suggesting that alteration of platelet releasate might be an important mechanism underlying trained immunity and may have clinical implications. Cite this article: Bone Joint Res 2022;11(2):73–81

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

Tranexamic acid (TXA), an inhibitor of fibrinolysis, reduces blood loss after total knee arthroplasty. However, its effect on minimally invasive total hip arthroplasty (THA) is not clear. We performed a prospective, randomised double-blind study to evaluate the effect of two intravenous injections of TXA on blood loss in patients undergoing minimally invasive THA. In total, 60 patients (35 women and 25 men with a mean age of 58.1 years; 17 to 84) who underwent unilateral minimally invasive uncemented THA were randomly divided into the study group (30 patients, 20 women and ten men with a mean age of 56.5 years; 17 to 79) that received two intravenous injections 1 g of TXA pre- and post-operatively (TXA group), and a placebo group (30 patients, 15 women and 15 men with a mean age of 59.5 years; 23 to 84). We compared the peri-operative blood loss of the two groups. Actual blood loss was calculated from the maximum reduction in the level of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism. The TXA group had a lower mean intra-operative blood loss of 441 ml (150 to 800) versus 615 ml (50 to 1580) in the placebo (p = 0.044), lower mean post-operative blood loss (285 ml (120 to 570) versus 392 ml (126 to 660) (p = 0.002), lower mean total blood loss (1070 ml (688 to 1478) versus 1337 ml (495 to 2238) (p = 0.004) and lower requirement for transfusion (p = 0.021). No patients in either group had symptoms of venous thromboembolism or wound complications. . This prospective, randomised controlled study showed that a regimen of two intravenous injections of 1 g TXA is effective for blood conservation after minimally invasive THA. Cite this article: Bone Joint J 2015;97-B:905–10

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

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. 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. 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). We conclude that 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

Introduction. Recently, oxidative stress has been implicated in the development of osteonecrosis. Here we focused on vitamins with marked antioxidant potency to see whether their use might prevent the development of osteonecrosis associated with corticosteroid administration. Methods. Fifteen male Japanese white rabbits weighing about 3.5 kg were injected once into the right gluteal muscle with methylprednisolone (MPSL) 40 mg/kg (S Group). Ten other rabbits, in addition, received consecutive daily intravenous injections of vitamin E 50 mg/kg starting from the day of MPSL administration (E Group), and 10 other animals similarly received consecutive daily intravenous injections of vitamin C 30 mg/kg (C Group). All animals were euthanized 2 weeks after MPSL administration, and femurs were extracted, and stained with hematoxylin-eosin. Blood levels of glutathione (GSH) were also measured. Results. In S Group, the osteonecrosis development rate was 93%, in contrast to 60% in C Group, and none in E Group (P<0.05). Also, GSH levels in both S and C Groups abruptly decreased from the 1st day after MPSL administration, whereas, in E Group, the decline in GSH levels was significantly suppressed on days 1 and 3 after MPSL administration (P<0.05). Conclusion. Vitamin E significantly inhibited the decrease in blood GSH levels noted in the groups not receiving it. Since GSH reflects oxidative stress in vivo, vitamin E administration may be preventative in the setting of this kind of corticosteroid-induced osteonecrosis rabbit model

INTRODUCTION. Adequate osseointegration of knee resurfacing implants for the treatment of focal cartilage defects is an important prerequisite for good clinical outcomes. Inadequate initial fixation and sustained micromotion may lead to osteolysis and ultimately implant failure. PET/CT with the bone seeking tracer 18F-sodium fluoride (18F-NaF) allows for localisation and quantification of abnormalities in bone metabolism. 18F-NaF PET/CT has been shown to correlate with loosening of implants in the hip and spine. Here, we asses osseointegration of the knee resurfacing implants using micro-computed tomography (µCT) and correlate µCT parameters to 18F-NaF uptake on PET/CT scans taken 3 and 12 weeks after surgery. We hypothesize that 18F-NaF uptake at 12 weeks and its relative decrease between 3 and 12 weeks correlates with osseointegration at 12 weeks postoperatively. Polymer implants with Young”s moduli approximately equal to- and below the Young's modulus of bone, with- and without surface modification were used in this study next to a control metal implant. METHODS. Five different osteochondral implants were implanted bilaterally in critically-sized osteochondral defects in 16 goats. At 3 and 12 weeks postoperatively, a 10-minute static PET/CT-scan (Philips, Gemini TF PET/CT) was made 60 minutes after intravenous injection of 18F-NaF. Image processing resulted in an overall bone metabolism parameter, i.e. standardized uptake value (SUV). A cylindrical region of interest was drawn around each implant to obtain the maximum SUV (SUVmax). Bone quality parameters were quantified in a cylinder surrounding the implant using µCT after sacrifice as a measure for osseointegration. The in vivo 18F-NaF PET/CT uptake parameters were correlated to the bone quality parameters. RESULTS. Implant osseointegration strongly varied for the different implants. Some implant groups exhibited very poor osseointegration with clear signs of osteolysis, while titanium implants exhibited good osseointegration. A strong correlation was observed between bone quality parameters as determined using µCT and SUVmax at 12 weeks. The SUVmax of the implants with poor osseointegration remained high, while implants with good osseointegration showed a relative decrease in SUVmax between 3 and 12 weeks. CONCLUSION. This study suggests that the SUVmax of PET/CT 12 weeks after surgery correlates well for the quality of osseointegration assessed on µCT 12 weeks after surgery. De relative decrease of SUVmax between the given time points had a strong correlation with the degree of osseointegration. In this study, large differences in the quality of osseointegration were observed. The role of surface modification, elasticity and micromotion still remain to be determined as well as if 18F-NaF is sensitive enough to discriminate between smaller differences and what the optimum time point would be to predict the ultimate osseointegration

1. A method of recording changes in bone blood-flow using a heated thermocouple is described. 2. Occlusion of the femoral artery or aorta decreases the blood-flow in the femoral metaphysis. 3. Occlusion of the femoral vein and intravenous injection of adrenaline, nor-adrenaline, acetylcholine, histamine or hexamethonium bromide increase the blood-flow in the femoral metaphysis

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

Antibiotic levels in bone and fat were measured in patients undergoing knee replacement to determine the time that should elapse between intravenous injection and tourniquet inflation. The tissue levels increased progressively with time, and there was wide variation in absorption rate between patients and between the two cephalosporins assessed. Five minutes should probably be left between systemic injection and inflation of the tourniquet, though two minutes may be long enough for drugs which are rapidly absorbed

1. in thirty-five patients, twenty-eight with classical haemophilia and seven with Christmas disease, arthropathy of the knee of various grades has been investigated by radioisotope scanning after intravenous injection of technetium, . 99m. Tc. 2. The abnormality of the colour scan particularly matches the clinical severity in acute haemarthrosis. 3. In patients with no clinically apparent joint disease the scan may be of value in the early detection of involvement. 4. The possible value of articular scanning in the selection of patients for treatment and in the assessment of the short and long term results is discussed

The clinical success of posterior lumbar interbody fusion (PLIF) may be limited by pseudarthrosis, defined as the absence of solid fusion 1 year after surgery. Currently, CT is used to diagnose pseudarthrosis but is not able to be conclusive earlier than 1 year after surgery. No non-invasive technique is available to reliably assess bone graft incorporation in the early phase after PLIF. Positron Emission Tomography (PET) is a nuclear imaging modality that is able to identify changes at the cellular and molecular level in an early stage, well before manifestation of anatomical changes. PET/CT with the bone seeking tracer . 18. F-fluoride allows localization and quantification of bone metabolism. This study investigates whether an . 18. F-fluoride PET/CT scan early after PLIF is able to predict the fusion status at 1 year postoperative on CT. Twenty patients after PLIF were enrolled after written informed consent. At 6 weeks and at 1 year after PLIF, intravenous injection of . 18. F-fluoride was followed by a static scan at 60 minutes (Philips, Gemini TF PET/CT). Processing of images resulted in a bone metabolism parameter i.e. standardized uptake value (SUV). This parameter was determined for 3 regions of interest (ROIs): the intervertebral disc space (IDS) and the upper and lower endplate (UE and LE, respectively) of the operated segment. Interbody fusion was scored on a diagnostic CT scan made 1 year postoperatively and was defined as the amount of complete bony bridges between vertebrae, i.e 0, 1 or 2. Based on these scores, patients were divided in either the pseudarthrosis group (score 0) or the fusion group (scores 1 and 2). Differences between groups were analyzed using the independent samples Mann-Whitney U-test. Ten patients were classified as pseudarthrosis (0 bridges: n=10) and 10 patients as fused (1 bridge: n=5, 2 bridges: n=5). Patients in the pseudarthrosis group showed significantly lower bone metabolism values in the IDS on the 6 weeks PET/CT scan compared to patients in the fusion group (SUV. IDS,6w. 13.3±5.62 for pseudarthrosis and 22.6±6.42 for the fusion group, p=0.003), whereas values at the endplates were similar (SUV. UE,6w. 20.3±5.85 for pseudarthrosis and 21.6±4.24 for the fusion group, p=0.282). Furthermore, only in the pseudarthrosis group, bone metabolism in the IDS was significantly lower than at the endplates (p=0.006). In the fusion group, bone metabolism in the IDS and at the endplates was similar (p=0.470). The PET/CT scan at 1 year postoperative showed that in the pseudarthrosis group, bone metabolism of the IDS remained lower compared to the endplates (SUV. IDS,1y. 13.2±4.37, SUV. UE,1y. 16.4±5.33, p=0.004), while in the fusion group, IDS and endplate bone metabolism was similar (SUV. IDS,1y. 13.6±2.91, SUV. UE,1y. 14.4±3.14, p=0.397). This study shows that low bone metabolism values in the IDS of the operated segment as seen on . 18. F-fluoride PET/CT 6 weeks after PLIF, is related to development of pseudarthrosis 1 year postoperatively. These results suggest that . 18. F-fluoride PET/CT might be an early diagnostic tool to identify patients prone to develop pseudarthrosis after PLIF

The acute childhood diseases haematogenous staphylococcal osteomyelitis and septic arthritis were studied concurrently using avian models which closely resemble the human diseases. Ultrastructural studies during the initial stages of bone and joint infection showed that adherence of bacteria to cartilage, bacterial proliferation, cartilage destruction and subsequent bacterial spread along the vascular channels within cartilage were common to both disease processes. Histological studies revealed that transphyseal blood vessels were present in the growing chickens and were a likely explanation for the frequency of the concurrence of acute osteomyelitis and adjacent joint infection following intravenous injection of bacteria. Transphyseal vessels provide a direct connection between the growth plate (physis) and epiphyseal cartilage supplying a route for bacteria to spread from an osteomyelitic focus in the metaphysis to the epiphysis and subsequently to the joint lumen

The effect of zoledronic acid on bone ingrowth was examined in an animal model in which porous tantalum implants were placed bilaterally within the ulnae of seven dogs. Zoledronic acid in saline was administered via a single post-operative intravenous injection at a dose of 0.1 mg/kg. The ulnae were harvested six weeks after surgery. Undecalcified transverse histological sections of the implant-bone interfaces were imaged with backscattered scanning electron microscopy and the percentage of available pore space that was filled with new bone was calculated. The mean extent of bone ingrowth was 6.6% for the control implants and 12.2% for the zoledronic acid-treated implants, an absolute difference of 5.6% (95% confidence interval, 1.2 to 10.1) and a relative difference of 85% which was statistically significant. Individual islands of new bone formation within the implant pores were similar in number in both groups but were 69% larger in the zoledronic acid-treated group. The bisphosphonate zoledronic acid should be further investigated for use in accelerating or enhancing the biological fixation of implants to bone

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

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

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

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