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Bone & Joint Research
Vol. 11, Issue 2 | Pages 73 - 81
22 Feb 2022
Gao T Lin J Wei H Bao B Zhu H Zheng X

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


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 61 - 61
1 Dec 2021
Hanberg P Bue M Öbrink-Hansen K Thomassen M S⊘balle K Stilling M
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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


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 91 - 91
1 Dec 2020
Hanberg P Bue M Öbrink-Hansen K Thomassen M S⊘balle K Stilling M
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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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_VIII | Pages 29 - 29
1 Mar 2012
Ichiseki T Kaneuji A Sugimori T Fukui K Kitamura K Mikami T Nakagawa S Matsumoto T
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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


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_3 | Pages 88 - 88
1 Apr 2018
Jeuken R Roth A Peters M van Rietbergen B Emans P
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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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XL | Pages 209 - 209
1 Sep 2012
Vittorio O Parchi P Raffa V Cuschieri A Lisanti M
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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


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_1 | Pages 70 - 70
1 Jan 2017
Peters M Brans B Wierts R Jutten L Weijers T Broos W Mottaghy F van Rhijn L Willems P
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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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 87 - 87
1 Feb 2012
Patel R Stygall J Harrington J Newman S Haddad F
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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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLI | Pages 70 - 70
1 Sep 2012
Kumar V Garg B Malhotra R
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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


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 80 - 80
1 Jan 2004
Daly KJ McInnes S Hutchinson S Lovell ME McCollum CN
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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


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 80 - 80
1 Jan 2004
Daly KJ Lovell ME Hutchinson S Hardicre J McCollum CN
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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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XVI | Pages 2 - 2
1 Apr 2012
Kumar DV
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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


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 526 - 526
1 Sep 2012
Kumar V Garg B Malhotra R
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Introduction. Tranexamic acid is an inhibitor of fibrinolysis that blocks the lysine-binding site of plasminogen to fibrin, and thereby decreases blood loss in patients undergoing surgery. Aims and objectives. A prospective, randomized, double-blind study was done on 100 patients undergoing primary cemented Unilateral Total Knee Arthroplasty to determine the effect of tranexamic acid on intra- and postoperative blood losses and on the transfusions requirements. Material and Methods. 100 patients undergoing unilateral cemented total knee Arthroplasty for osteoarthritis were enrolled for the study. All total knee replacement was done under combined spinal epidural anaesthesia with the use of tourniquet. 100 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 release of tourniquiet. The 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. Results. Patients receiving tranexamic acid had a mean postoperative blood loss of 175 ml(range, 130–310ml) versus 330 ml (range, 210–460ml) (p value<0.05), and a total need for 3 blood transfusions versus 15. Only 3 out 50 patients in tranexamic acid group required blood transfusion whereas 12 out of 50 patients in the placebo group required transfusion. In the group receiving placebo the mean fall in hemoglobin was 2.1g/dl (range, 1.5–3.2) and in the group treated with tranexamic acid 1.3 g/dl (0.9–2) (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. Conclusion. Tranexamic acid 15 mg/kg given as a single bolus dose reduces blood loss, and transfusion requirements in unilateral primary cemented total kneearthroplasty without any increased risk of thrombus formation


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 281 - 281
1 Jul 2014
Potapova I David E Laschke M Bischoff M Richards R Moriarty T
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Summary. The two-step labeling protocol using Lysostaphin and bio-orthogonal click chemistry for staining bacteria is described. The click protocol is efficient in labeling staphylococci and is non-toxic. This protocol promises the efficient of infections that are difficult to assess by conventional imaging. Introduction. Infection diagnostics in clinics is time consuming, invasive and relays on microbiological cultures. New probes and labeling protocols enabling rapid and specific detection of infection in vivo shall improve the situation. We investigated the potential of a new click labeling protocol to detect staphylococci. Azido (N3) - modified Lysostaphin and DIBO (Di-benzocyclooctyne) - dye were used in the two-step bacteria-labeling protocol. N3 and DIBO were the counterparts of the bioorthogonal “click” reaction. In the first step, Lysostaphin-N3 bound to Staphylococcus aureus. In the second step, N3 clicked to DIBO thus achieving S. aureus selective labeling. Methods. S. aureus NCTC 10788 and E. coli NCTC 12241 (from National Collection of Type Cultures), primary sheep osteoblasts and C57BL/6 mice were used for this study. DIBO-Alexa488 (Invitrogen ®), DyeLight488 (Thermofisher ®), NHS-N3 (Lumiprobe ®), Lysostaphin (Sigma-Aldrich ®) were purchased. In vitro we used standard microbiological protocols to assess antimicrobial and labeling activity of the “click” probe (Lysostaphin-N3 plus DIBO-dye), one-step-labeled Lysostaphin-Dye and non-labeled Lysostaphin. Flow cytometry, Fluorescence microscopy, and Spectrophotometry were employed to measure binding of the probes to bacteria. The cytotoxicity of the probes on osteoblasts was performed using Presto Blue Cell Viability test (Invitrogen ®). In vivo we used Fluorescence Intravital Microscopy and mice with dorsal skin-fold chambers (approved by the local governmental animal care committee). Subsequently to anesthesia each mouse received S. aureus strain Cowan I intravenously. This was followed by intravenous injections of the test probes. Results. Lysostaphin-N3 partially lost its antimicrobial property if compare to Lysostaphin alone, but still bound to S. aureus efficiently and clicked DIBO-dye afterwards. There was no significant cytotoxicity of “click” reagents on sheep osteoblasts. In vitro the two-step labeling with Lysostaphin-Click was more efficient than the one-step labeling with Lysostaphin-Dye. In vivo the two-step and one-step labeling differed rather qualitatively. In the two-step protocol the “click” probe labeled bacteria adherent to the blood vessels and bacteria extravasated into the soft tissue around 30 minutes post-injection. In the one-step protocol bacteria were labeled quickly (within minutes) in the blood flow and on the blood vessels but not in the soft tissue. Discussion/Conclusion. Effective labeling bacteria with the click probe could be useful for a quantitative and selective assessment of infection, in particular for staphylococci infections, which are common in orthopedic implants but often difficult to detect. The one and two-step protocols successfully labeled bacteria in mice but the labeling was different. In the one-step protocol bacteria were labeled in the blood flow quickly; in the two-step protocol bacteria adherent to the blood vessels and extravasated into the soft tissue bacteria were labeled with a delay


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 17 - 18
1 Mar 2008
Patel R Stygall J Harrington J Harrison M Newman S Haddad F
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To quantify the intraoperative cerebral microemboli load during primary total knee arthroplasty (TKA) using transcranial Doppler ultrasound and to investigate whether a patent foramen ovale influences cerebral embolic load in general. Patients undergoing primary TKA, with no history of stroke, TIA, ongoing CNS disease or alcoholism were included. All operations were carried out under a standardised general anaesthetic and performed by two consultant orthopaedic surgeons. Microemboli l oad was recorded, using transcranial Doppler ultrasound (TCD), onto VHS tape for subsequent playback and analysis. Patent foramen ovale detection was performed using bolus intravenous injection of agitated saline followed by valsalva manoeuvre technique and TCD. Timing of specific surgical steps was recorded for each operation and emboli load calculated for that period. Results: 50 TKA patients were studied (31 females, 19 males); 28 right and 22 left TKAs were performed. Cerebral microembolisation occurred in 19 patients (42%). Mean microembolic load was 3.56 per patient (range 0–21). PFO was detected in 9 patients (18%). Two thirds of PFO positive patients displayed cerebral microemboli. However, 36.6% (n=15) of PFO negative patients also displayed microemboli intraoperatively. Deflation of the tourniquet was followed by a larger microembolic load than the other phases of the operation. Conclusion: Intraoperative cerebral microembolisation occurs in a significant proportion of patients during total knee arthroplasty. The presence of a patent foramen ovale does not appear to influence the incidence microemboli intraoperatively. Specific surgical activities are associated with generating greater embolic loads. These questions will be comprehensively assessed in the larger study currently underway


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_I | Pages 171 - 171
1 Mar 2008
Kim K Kaneko K Iwase M Taiki
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Osteoprotegerin (OPG) has been reported to be a novel protein that can suppress osteoclast differentiation and activation. This study examined the therapeutic effects of OPG on established periprosthetic osteolysis in a rat model. A bone cement prosthesis was inserted into the rat femur and polyethylene particles were continuously infused into the knee joint using an osmotic pump. After osteolysis was established in four weeks, rats were intravenously injected with vehicle (control group) or 1 mg/kg of OPG (OPG-1 group) or 10 mg/kg of OPG (OPG-10 group) every week until they were sacrificed at 8 weeks. Effects of direct injections of OPG into the knee joint were also investigated. Periprosthetic bone resorption was evaluated with bone mineral density and histomorphometric analysis of membranes composed of total area of interface membrane and inflammatory grading. Radiographs were evaluated for focal osteolysis with a blind manner. Periprosthetic bone resorption was significantly suppressed in OPG-10 group compared to the other groups (p < 0.05). Histomorphometric analyses showed less total area as well as less inflammatory grading of the interface membrane in OPG-10 group compared to other groups (p < 0.01). Radiographic osteolysis appeared to decrease in number in OPG-10 group. Direct injections of OPG into the knee joint appeared to be more effective compared to intravenous injections. The present study demonstrates that OPG has significantly restored the established periprosthetic osteolysis in our animal model. OPG may be a possible agent to retain the bone stock before revision surgery for failed prostheses. Conclusion: This study demonstrates that osteoprotegerin suppresses the progression of periprosthetic osteolysis and restores bone stock in a rat model


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 21 - 21
1 Mar 2006
Varitimidis S Poultsides L Dailiana Z Passias A Kitsiopoulou E Malizos K
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Introduction: Surgery in the foot and ankle is usually performed under general or spinal anaesthesia. Peripheral nerve blocking is gaining the preference of both surgeons and patients. The aim of this study is to evaluate the adequacy of anaesthesia with the method of triple nerve blocking at the region of the knee. Materials and methods: One hundred and forty-four patients (79 men and 65 women) that were diagnosed with ankle and foot injuries or diseases underwent surgery using triple nerve blocking at the knee region as a method of anaesthesia. Surgical procedures included bone and soft tissue procedures and especially fracture fixation, osteotomies, tendon repairs, neuroma and tumor excisions, nerve decompressions and arthrodeses. The common peroneal, tibial and saphenous nerves were blocked with injection of 8 ml ropivacaine 2% for each nerve. The injection was performed by an Orthopaedic surgeon with the use of a neurostimulator. An anesthesiologist was available when necessary. Results: Ninety-four patients tolerated the procedure without the need of additional injection of anaesthesia or analgesia. In 45 patients additional injection of local anesthetic was necessary. Five patients needed intravenous injection of analgesia in order to complete the procedure. Patients were mobilized the day of surgery, reducing in that way hospital stay. Hospitalization ranged from 0 to 1 days with 58 patients discharged the day of the operation. No complication related to the injection of the anestheric was observed. Conclusion: Triple nerve blocking at the knee, as a method of anaesthesia, is proposed for certain procedures in the foot and ankle; it allows early mobilization of patients and reduces length of hospital stay. If the neurostimulator is used appropriately, the rate of patients that needs additional analgesia intraoperatively is diminished and no adverse effects of the local anestheric are observed. Complications observed with the practice of spinal or general anesthesia are avoided


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 232 - 232
1 Mar 2004
Patel R Stygall J Harrington J Newman S Haddad F
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Aims: To compare the intraoperative cerebral microemboli load between primary total hip (THA) and knee arthroplsty (TKA) using transcranial Doppler ultrasound and to investigate whether a patent foramen ovale influences cerebral embolic load in general. The timing of the microemboli will be related to certain surgical activities to determine if a specific relationship exists. Methods: Patients undergoing primary TKA or THA, with no history of stroke, TIA, ongoing CNS disease or alcoholism included. All operations carried out under a standardised general anaesthetic and performed by two consultant orthopaedic surgeons. Microemboli load recorded, using transcranial Doppler ultrasound (TCD), onto VHS tape for subsequent playback and analysis. Patent foramen ovale detection performed using bolus intravenous injection of agitated saline followed by valsalva manoeuvre technique and TCD. Timing of specific surgical steps recorded for each operation and emboli load calculated for that period. Results: 20 THA and 20 TKA patients were studied. Cerebral microembolisation occurred in 50% of THA and 40% of TKA patients. Total microembolic load for THA patients was 137 (range=0–83) and 50 (range=0–21) for TKA patients. Prevalence of PFO in the THA group was 35%, and 20% in the TKA group. 57.1% of PFO positive THA patients and 75% of PFO positive TKA patients displayed microemboli. Insertion of the femoral component in THA and release of the tourniquet in TKA were associated with higher cerebral microemboli load. Conclusion: Intraoperative cerebral microembolisation occurs in almost half of patients during hip and knee arthroplasty. Patients who have a PFO appear more likely to be associated with cerebral embolisation. Specific surgical activities are associated with larger embolic loads


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 78 - 78
1 Jan 2004
Patel RV Stygall J Harrington J Harrison MG Newman S Haddad FS
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Aims: To quantify the intraoperative cerebral microemboli load during primary total hip arthroplasty (THA) using transcranial Doppler ultrasound and to investigate whether a patent foramen ovale influences cerebral embolic load in general. The timing of the microemboli will be related to certain surgical activities to determine if a specific relationship exists. Methods: Patients undergoing primary THA, with no history of stroke, TIA, ongoing CNS disease or alcoholism were included. All operations were carried out under a standardised general anaesthetic and performed by two consultant orthopaedic surgeons. Microemboli load was recorded, using transcranial Doppler ultrasound (TCD), onto VHS tape for subsequent playback and analysis. Patent foramen ovale detection was performed using bolus intravenous injection of agitated saline followed by valsalva manoeuvre technique and TCD. Timing of specific surgical steps was recorded for each operation and emboli load calculated for that period. Results: 25 THA patients were studied (18 females, 7 males) 16 right and 9 left THA’s were performed. Cerebral microembolisation occurred in 10 patients (40%). Mean microembolic load was 5.52 per patient (range = 0–83). PFO was detected in 8 patients (32%). 37.5% of PFO positive patients displayed cerebral microemboli. However, 41.1% of PFO negative patients also displayed microemboli intraoperatively. Insertion of the femoral component was associated with generating a larger microembolic load than the other phases of the operation. Conclusion: Intraoperative cerebral microembolisation occurs in a significant proportion of patients during total hip arthroplasty. The presence of a patent foramen ovale does not appear to influence the incidence microemboli intraoperatively. Specific surgical activities are associated with generating greater embolic loads. These questions will be comprehensively assessed in the larger study currently underway