Session 4: Experimental
18. November
11:00 - 12:00
Lokale: 01+02
Chairmen: Mathias Bünger & Christian Wong
Josephine Olsen Kipp, Pelle Hanberg, Josefine Slater, Line Mřller Nielsen, Stig Storgaard Jakobsen, Maiken Stilling, Mats Bue
Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Horsens Regional Hospital; Department of Clinical Biochemistry, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital
Background: Systemic perioperative vancomycin may not provide sufficient prophylactic target-site concentrations in the prevention of prosthetic joint infections. Intraosseous vancomycin potentially provides high target- site concentrations.
Aim: The objective of the present study was to evaluate the local bone and tissue concentrations following tibial intraosseous vancomycin administration in a porcine model.
Materials and Methods: Eight pigs received 500 mg diluted vancomycin (50 mg/mL) through an intraosseous cannula into the proximal tibial cancellous bone. Microdialysis was applied for sampling of vancomycin concentrations in adjacent tibial cancellous bone, in cortical bone, in the intramedullary canal of the diaphysis, in the synovial fluid of the knee joint, and in the subcutaneous tissue. Plasma samples were obtained as a systemic reference. Samples were collected for 12 hours.
Results: High vancomycin concentrations were found in the tibial cancellous bone with a mean peak drug concentration of 1,236 (range 28–5,295) µg/mL, which remained high throughout the sampling period. The mean (standard deviation) peak drug concentration in plasma was 19 (2) µg/mL, which was obtained immediately after administration. Peak drug concentration, time to peak drug concentration, and area under the concentration–time curve were within the same range in the intramedullary canal, the synovial fluid of the knee, and the subcutaneous tissue.
Interpretation / Conclusion: Tibial intraosseous administration of vancomycin provided high concentrations in tibial cancellous bone throughout a 12-hour period but with an unpredictable and wide range of peak concentration. The systemic absorption was high and immediate, thus mirroring an intravenous administration. Low mean concentrations were found in all the remaining compartments.
Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Horsens Regional Hospital; Department of Clinical Biochemistry, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital
Background: Systemic perioperative vancomycin may not provide sufficient prophylactic target-site concentrations in the prevention of prosthetic joint infections. Intraosseous vancomycin potentially provides high target- site concentrations.
Aim: The objective of the present study was to evaluate the local bone and tissue concentrations following tibial intraosseous vancomycin administration in a porcine model.
Materials and Methods: Eight pigs received 500 mg diluted vancomycin (50 mg/mL) through an intraosseous cannula into the proximal tibial cancellous bone. Microdialysis was applied for sampling of vancomycin concentrations in adjacent tibial cancellous bone, in cortical bone, in the intramedullary canal of the diaphysis, in the synovial fluid of the knee joint, and in the subcutaneous tissue. Plasma samples were obtained as a systemic reference. Samples were collected for 12 hours.
Results: High vancomycin concentrations were found in the tibial cancellous bone with a mean peak drug concentration of 1,236 (range 28–5,295) µg/mL, which remained high throughout the sampling period. The mean (standard deviation) peak drug concentration in plasma was 19 (2) µg/mL, which was obtained immediately after administration. Peak drug concentration, time to peak drug concentration, and area under the concentration–time curve were within the same range in the intramedullary canal, the synovial fluid of the knee, and the subcutaneous tissue.
Interpretation / Conclusion: Tibial intraosseous administration of vancomycin provided high concentrations in tibial cancellous bone throughout a 12-hour period but with an unpredictable and wide range of peak concentration. The systemic absorption was high and immediate, thus mirroring an intravenous administration. Low mean concentrations were found in all the remaining compartments.
Jens Rithamer Jakobsen, Peter Schjerling, Michael Kjaer, Abigail Mackey, Michael Rindom Krogsgaard
Department of sports traumatology M51, Bispebjerg-Frederiksberg Hospital*; Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital, Copenhagen*; Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen *Departments are part of IOC Research Center Copenhagen.
Background: The myotendinous junction (MTJ) is the region where strain injuries most often occur. Clinically, the risk for these injuries can be reduced through specific resistance training. This positive effect may be caused by changes in the concentration of structural proteins, leading to a strengthening of the MTJ. However, specific knowledge about the effect on the structure and tissue composition of the MTJ of resistance exercise is sparse. In order to study changes in protein content or gene expression at the MTJ it is necessary to isolate MTJ from the skeletal muscle and tendon to avoid that results from different tissues are mixed.
Aim: We aimed to develop a method to divide a sample taken from the MTJ into its three components: muscle, tendon and MTJ.
Materials and Methods: Samples were collected from the superficial digitorum flexor muscle from 20 horses and frozen routinely for immunohistochemistry. In frozen form each specimen was manually sliced parallel to MTJ into 10 µm thick sections and sampled for further processing. By controlling every 20th section visually it was noted whether the section contained muscle, MTJ or tendon. RT-PCR was performed on the collected sections identifying mRNA targets regularly used in the study of skeletal muscle and tendon. A Principle Component Analysis (PCA) and a t- distributed stochastic neighboring plot (t-SNE) were made on all the results to evaluate how well the different tissue regions had been isolated.
Results: It was possible visually to group the samples according to the three tissues. The t-SNE plot confirmed that the MTJ samples grouped specifically and were very similar in relation to their expression of the mRNA targets.
Interpretation / Conclusion: It was possible by this method to divide a specimen from the MTJ into muscle-, tendon- and MTJ-tissue. It is a cheap and specific method which is useful in studies looking into changes introduced at the MTJ following resistance exercise and experimental set- ups.
Department of sports traumatology M51, Bispebjerg-Frederiksberg Hospital*; Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital, Copenhagen*; Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen *Departments are part of IOC Research Center Copenhagen.
Background: The myotendinous junction (MTJ) is the region where strain injuries most often occur. Clinically, the risk for these injuries can be reduced through specific resistance training. This positive effect may be caused by changes in the concentration of structural proteins, leading to a strengthening of the MTJ. However, specific knowledge about the effect on the structure and tissue composition of the MTJ of resistance exercise is sparse. In order to study changes in protein content or gene expression at the MTJ it is necessary to isolate MTJ from the skeletal muscle and tendon to avoid that results from different tissues are mixed.
Aim: We aimed to develop a method to divide a sample taken from the MTJ into its three components: muscle, tendon and MTJ.
Materials and Methods: Samples were collected from the superficial digitorum flexor muscle from 20 horses and frozen routinely for immunohistochemistry. In frozen form each specimen was manually sliced parallel to MTJ into 10 µm thick sections and sampled for further processing. By controlling every 20th section visually it was noted whether the section contained muscle, MTJ or tendon. RT-PCR was performed on the collected sections identifying mRNA targets regularly used in the study of skeletal muscle and tendon. A Principle Component Analysis (PCA) and a t- distributed stochastic neighboring plot (t-SNE) were made on all the results to evaluate how well the different tissue regions had been isolated.
Results: It was possible visually to group the samples according to the three tissues. The t-SNE plot confirmed that the MTJ samples grouped specifically and were very similar in relation to their expression of the mRNA targets.
Interpretation / Conclusion: It was possible by this method to divide a specimen from the MTJ into muscle-, tendon- and MTJ-tissue. It is a cheap and specific method which is useful in studies looking into changes introduced at the MTJ following resistance exercise and experimental set- ups.
Andrea René Jřrgensen, Pelle Hanberg, Mats Bue, Maja Brřgger Thomassen, Pedersen Jřrgensen , Maiken Stilling
Aarhus Microdialysis Research Group, Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Horsens Regional Hospital; Department of Infectious Diseases, Aarhus University Hospital; Department of Clinical Medicine, Aarhus University; Department of Orthopaedic Surgery, Aarhus University Hospital
Background: Surgical site infection is a severe complication to orthopaedic surgery, which can prolong admission and increase cost. Optimal perioperative antimicrobial prophylactic treatment is a key factor in preventing surgically related infections.
Aim: This study evaluated target tissue concentrations of double dose cefuroxime administered intravenously as either one 15 min infusion of 3,000 mg (Group 1) or two single 15 min infusions of 1,500 mg administered 4 h apart (Group 2).
Materials and Methods: Sixteen pigs were randomised into two groups of eight. Cortical and cancellous bone, synovial fluid of the knee joint and subcutaneous adipose tissue concentrations were measured based on sampling via microdialysis. Plasma samples were collected as a reference. Comparison of the groups was based on time with concentrations above relevant minimal inhibitory concentrations ( fT>MIC) of 4 µg/mL.
Results: The mean time fT>MIC (4 µg/mL) across compartments was longer for Group 2 (280–394 min) than for Group 1 (207–253 min) (p<0.01). Cortical bone showed a tendency towards longer f T>MIC (4 µg/mL) in Group 2 (280 min) than in Group 1 (207 min) (p=0.053). Within 50 min after administration, the mean concentration of 4 µg/mL was reached in all compartments for both groups. The mean concentrations decreased below 4 µg/mL after approximately 4 h (Group 1) and 3 h (Group 2) from initiation of administration (time zero).
Interpretation / Conclusion: During an 8 h interval, double-dose cefuroxime administered as 2 × 1,500 mg with a 4 h interval provides longer time above MIC breakpoint for Staphylococcus aureus (4 µg/mL) than a single bolus of 3,000 mg cefuroxime. To maintain sufficient tissue concentrations during longer surgeries, re- administration of cefuroxime (1,500 mg) should be considered 3 h after the first administration.
Aarhus Microdialysis Research Group, Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Horsens Regional Hospital; Department of Infectious Diseases, Aarhus University Hospital; Department of Clinical Medicine, Aarhus University; Department of Orthopaedic Surgery, Aarhus University Hospital
Background: Surgical site infection is a severe complication to orthopaedic surgery, which can prolong admission and increase cost. Optimal perioperative antimicrobial prophylactic treatment is a key factor in preventing surgically related infections.
Aim: This study evaluated target tissue concentrations of double dose cefuroxime administered intravenously as either one 15 min infusion of 3,000 mg (Group 1) or two single 15 min infusions of 1,500 mg administered 4 h apart (Group 2).
Materials and Methods: Sixteen pigs were randomised into two groups of eight. Cortical and cancellous bone, synovial fluid of the knee joint and subcutaneous adipose tissue concentrations were measured based on sampling via microdialysis. Plasma samples were collected as a reference. Comparison of the groups was based on time with concentrations above relevant minimal inhibitory concentrations ( fT>MIC) of 4 µg/mL.
Results: The mean time fT>MIC (4 µg/mL) across compartments was longer for Group 2 (280–394 min) than for Group 1 (207–253 min) (p<0.01). Cortical bone showed a tendency towards longer f T>MIC (4 µg/mL) in Group 2 (280 min) than in Group 1 (207 min) (p=0.053). Within 50 min after administration, the mean concentration of 4 µg/mL was reached in all compartments for both groups. The mean concentrations decreased below 4 µg/mL after approximately 4 h (Group 1) and 3 h (Group 2) from initiation of administration (time zero).
Interpretation / Conclusion: During an 8 h interval, double-dose cefuroxime administered as 2 × 1,500 mg with a 4 h interval provides longer time above MIC breakpoint for Staphylococcus aureus (4 µg/mL) than a single bolus of 3,000 mg cefuroxime. To maintain sufficient tissue concentrations during longer surgeries, re- administration of cefuroxime (1,500 mg) should be considered 3 h after the first administration.
Magnus A. Hvistendahl, Mats Bue, Pelle Hanberg, Alexander Emil Kaspersen, Maiken Stilling, Kristian Hřy
Department of Clinical Medicine, Aarhus University; Aarhus Microdialysis Research Group, Aarhus University Hospital; Department of Orthopedic Surgery, Aarhus University Hospital
Background: Postoperative infection following spine surgery can have devastating complications. Perioperative antibiotic prophylaxis plays a key role in lowering the risk of acquiring an infection. The antibiotic target tissue concentrations should, as a minimum, exceed relevant minimal inhibitory concentrations (MIC) for the duration of the surgery in all exposed tissues. Previous studies have primarily measured antibiotic concentrations in the anterior column (AC) of the spine, however the majority of spine surgeries are performed in the posterior column (PC) of the spine.
Aim: The objective of this study was to compare the perioperative tissue concentrations of cefuroxime in the AC and PC in posterior open lumbar spine surgery.
Materials and Methods: Posterior open lumbar spine surgery was conducted on 8 female pigs. Microdialysis catheters were placed for sampling in the AC (vertebral body) and PC (posterior arch) within the same vertebrae (L5). Cefuroxime (1.5 g) was administered intravenously over 10 min and microdialysates and plasma samples were continuously obtained over 8 hours. Cefuroxime concentrations were quantified by Ultra High-Performance Liquid Chromatography. The primary endpoint was time above cefuroxime clinical breakpoint MIC for Staphylococcus Aureus (T>MIC (4 µg/mL)).
Results: Mean T>MIC (4 µg/mL) [95%CI] were 104 [85–123], 93 [73-112] and 123 min [104-142] in the AC, PC and plasma, respectively. Tissue penetration (AUCtissue/AUCplasma) [95%CI] was incomplete for both the AC (0.53 [0.42 - 0.64]) and PC (0.36 [0.25-0.47]) with the lowest penetration to the PC (p=0.048). Area under the concentration-time curve from 0 to last measured value (AUC0-last) was higher in the AC compared with the PC (p=0.05).
Interpretation / Conclusion: Cefuroxime penetrated heterogeneously within the same vertebrae, but the T>MIC were comparable between the anterior and posterior column. The mean cefuroxime concentrations decreased below 4 µg/mL after 93 min (PC) and 104 min (AC) after a single dose administration. This is shorter than the duration of most spine surgeries, and therefore alternative dosing regimens should be considered in posterior open lumbar spine surgeries lasting more than 90 min.
Department of Clinical Medicine, Aarhus University; Aarhus Microdialysis Research Group, Aarhus University Hospital; Department of Orthopedic Surgery, Aarhus University Hospital
Background: Postoperative infection following spine surgery can have devastating complications. Perioperative antibiotic prophylaxis plays a key role in lowering the risk of acquiring an infection. The antibiotic target tissue concentrations should, as a minimum, exceed relevant minimal inhibitory concentrations (MIC) for the duration of the surgery in all exposed tissues. Previous studies have primarily measured antibiotic concentrations in the anterior column (AC) of the spine, however the majority of spine surgeries are performed in the posterior column (PC) of the spine.
Aim: The objective of this study was to compare the perioperative tissue concentrations of cefuroxime in the AC and PC in posterior open lumbar spine surgery.
Materials and Methods: Posterior open lumbar spine surgery was conducted on 8 female pigs. Microdialysis catheters were placed for sampling in the AC (vertebral body) and PC (posterior arch) within the same vertebrae (L5). Cefuroxime (1.5 g) was administered intravenously over 10 min and microdialysates and plasma samples were continuously obtained over 8 hours. Cefuroxime concentrations were quantified by Ultra High-Performance Liquid Chromatography. The primary endpoint was time above cefuroxime clinical breakpoint MIC for Staphylococcus Aureus (T>MIC (4 µg/mL)).
Results: Mean T>MIC (4 µg/mL) [95%CI] were 104 [85–123], 93 [73-112] and 123 min [104-142] in the AC, PC and plasma, respectively. Tissue penetration (AUCtissue/AUCplasma) [95%CI] was incomplete for both the AC (0.53 [0.42 - 0.64]) and PC (0.36 [0.25-0.47]) with the lowest penetration to the PC (p=0.048). Area under the concentration-time curve from 0 to last measured value (AUC0-last) was higher in the AC compared with the PC (p=0.05).
Interpretation / Conclusion: Cefuroxime penetrated heterogeneously within the same vertebrae, but the T>MIC were comparable between the anterior and posterior column. The mean cefuroxime concentrations decreased below 4 µg/mL after 93 min (PC) and 104 min (AC) after a single dose administration. This is shorter than the duration of most spine surgeries, and therefore alternative dosing regimens should be considered in posterior open lumbar spine surgeries lasting more than 90 min.
Pelle Hanberg, Mats Bue, Kristina Öbrink-Hansen, Maja Thomassen, Kjeld Sřballe, Maiken Stilling
Department of Orthopaedic Surgery, Horsens Regional Hospital Orthopaedic Research Unit, Aarhus University Hospital Department of Clinical Medicine, INCUBA, Aarhus University Department of Infectious Diseases, Aarhus University Hospital Department of Orthopaedic Surgery, Aarhus University Hospital
Background: Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important.
Aim: The objective of this study was to evaluate cefuroxime subcutaneous tissue and calcaneal cancellous bone concentration during three clinically relevant tourniquet application scenarios.
Materials and Methods: Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in subcutaneous tissue and calcaneal cancellous bone, 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. The primary endpoint was time above cefuroxime clinical breakpoint MIC for Staphylococcus aureus (T>MIC (4 µg/mL)).
Results: Cefuroxime concentrations were maintained above the 4 µg/mL in subcutaneous tissue and calcaneal cancellous bone 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.
Interpretation / Conclusion: 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.
Department of Orthopaedic Surgery, Horsens Regional Hospital Orthopaedic Research Unit, Aarhus University Hospital Department of Clinical Medicine, INCUBA, Aarhus University Department of Infectious Diseases, Aarhus University Hospital Department of Orthopaedic Surgery, Aarhus University Hospital
Background: Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important.
Aim: The objective of this study was to evaluate cefuroxime subcutaneous tissue and calcaneal cancellous bone concentration during three clinically relevant tourniquet application scenarios.
Materials and Methods: Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in subcutaneous tissue and calcaneal cancellous bone, 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. The primary endpoint was time above cefuroxime clinical breakpoint MIC for Staphylococcus aureus (T>MIC (4 µg/mL)).
Results: Cefuroxime concentrations were maintained above the 4 µg/mL in subcutaneous tissue and calcaneal cancellous bone 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.
Interpretation / Conclusion: 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.
Alexander Emil Kaspersen, Pelle Emil Hanberg, Magnus A. Hvistendahl, Mats Bue, Kristian Hřy, Maiken Stilling
Spine Section, Department of Orthopaedic Surgery, Aarhus University Hospital; Aarhus Microdialysis Research Group, Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Clinical Medicine, Faculty of Health, Aarhus University
Background: Cefuroxime is used as surgical prophylaxis of intra- and extradural infections in relation to spine surgery. Bacterial eradication requires target tissue concentrations of cefuroxime above minimum inhibitory concentrations (MICs) of relevant pathogens for a sufficient amount of time. Microdialysis can continuously sample local antibiotic tissue concentrations in vivo and measure cefuroxime concentrations in intra- and extradural tissues.
Aim: To quantify concentrations of cefuroxime in intradural (spinal cord, cerebrospinal fluid) and extradural (epidural space) compartments in the lumbar spine of a porcine model using microdialysis.
Materials and Methods: Eight female pigs were anaesthetised and laminectomised at L3-4 by a posterior open surgical approach. Microdialysis catheters were placed for sampling in the spinal cord, cerebrospinal fluid, and epidural space. Cefuroxime (1500 mg) was administered intravenously over 10 minutes. Microdialysates and plasma were obtained continuously over 8 hours. Cefuroxime concentrations were determined by ultra-high performance liquid chromatography. The primary endpoint was time above cefuroxime clinical breakpoint MIC for Staphylococcus aureus (T>MIC of 4 µg/ml), and was compared between compartments using mixed effect-models and post hoc pairwise t- tests.
Results: Mean T>MIC (4 µg/ml) with 95% confidence interval (CI) were 58 (15–102), 0 (0–0), 115 (85–145), and 123 (106–141) minutes in spinal cord, cerebrospinal fluid, epidural space, and plasma, respectively. Tissue penetration (AUCtissue/AUCplasma) with 95% CI were 0.32 (0.13–0.51), 0.09 (0.03–0.15), and 0.63 (0.43–0.83) for spinal cord, cerebrospinal fluid, and epidural space, respectively. T>MIC (4 µg/ml) as well as tissue penetration were lower for the intradural compartments compared to the extradural.
Interpretation / Conclusion: Cefuroxime concentrations and T>MIC (4 µg/ml) were lower in intradural compartments compared to extradural, suggesting a compromising effect of the blood-brain barrier. In terms of T>MIC, single-dose cefuroxime (1500 mg) is inadequate for surgical prophylaxis of intradural infections, but adequate for surgical prophylaxis of extradural infections in spine surgery lasting a maximum 85 minutes.
Spine Section, Department of Orthopaedic Surgery, Aarhus University Hospital; Aarhus Microdialysis Research Group, Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Clinical Medicine, Faculty of Health, Aarhus University
Background: Cefuroxime is used as surgical prophylaxis of intra- and extradural infections in relation to spine surgery. Bacterial eradication requires target tissue concentrations of cefuroxime above minimum inhibitory concentrations (MICs) of relevant pathogens for a sufficient amount of time. Microdialysis can continuously sample local antibiotic tissue concentrations in vivo and measure cefuroxime concentrations in intra- and extradural tissues.
Aim: To quantify concentrations of cefuroxime in intradural (spinal cord, cerebrospinal fluid) and extradural (epidural space) compartments in the lumbar spine of a porcine model using microdialysis.
Materials and Methods: Eight female pigs were anaesthetised and laminectomised at L3-4 by a posterior open surgical approach. Microdialysis catheters were placed for sampling in the spinal cord, cerebrospinal fluid, and epidural space. Cefuroxime (1500 mg) was administered intravenously over 10 minutes. Microdialysates and plasma were obtained continuously over 8 hours. Cefuroxime concentrations were determined by ultra-high performance liquid chromatography. The primary endpoint was time above cefuroxime clinical breakpoint MIC for Staphylococcus aureus (T>MIC of 4 µg/ml), and was compared between compartments using mixed effect-models and post hoc pairwise t- tests.
Results: Mean T>MIC (4 µg/ml) with 95% confidence interval (CI) were 58 (15–102), 0 (0–0), 115 (85–145), and 123 (106–141) minutes in spinal cord, cerebrospinal fluid, epidural space, and plasma, respectively. Tissue penetration (AUCtissue/AUCplasma) with 95% CI were 0.32 (0.13–0.51), 0.09 (0.03–0.15), and 0.63 (0.43–0.83) for spinal cord, cerebrospinal fluid, and epidural space, respectively. T>MIC (4 µg/ml) as well as tissue penetration were lower for the intradural compartments compared to the extradural.
Interpretation / Conclusion: Cefuroxime concentrations and T>MIC (4 µg/ml) were lower in intradural compartments compared to extradural, suggesting a compromising effect of the blood-brain barrier. In terms of T>MIC, single-dose cefuroxime (1500 mg) is inadequate for surgical prophylaxis of intradural infections, but adequate for surgical prophylaxis of extradural infections in spine surgery lasting a maximum 85 minutes.
Kris Tvilum Chadwick Hede, Bjřrn Borsře Christensen, Morten Lykke Olesen, Jesper Skovhus Thomsen, Casper Bindzus Foldager, Wei Seong Toh, Sai Kiang Lim, Martin Carře Lind
Orthopedic Research Laboratory, Aarhus University Hospital; Orthopedic Research Laboratory, Aarhus University Hospital; Orthopedic Research Laboratory, Aarhus University Hospital; Department of Biomedicine, Aarhus University; Orthopedic Research Laboratory, Aarhus University Hospital; Faculty of Dentistry, National University of Singapore AND Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research; Sports Trauma Clinic, Aarhus University Hospital
Background: Recently several bone marrow stimulation enhancement treatments have been developed to improve the cartilage repair after bone marrow stimulation.
Aim: The aim of the study was to evaluate the effects of mesenchymal stem cell- extracellular vesicles (MSC-EVs) on chondrocyte proliferation in vitro and on cartilage repair in vivo following bone marrow stimulation (BMS) of focal chondral defects of the knee.
Materials and Methods: Six adult Göttingen minipigs received two chondral defects in each knee. The pigs were randomized to treatment with either BMS combined with MSC-EVs or BMS combined with phosphate-buffered saline (PBS). Intra-articular injections MSC-EVs or PBS were performed immediately after closure of the surgical incisions, and at 2 and 4 weeks post-operatively. Repair was evaluated after 6 months with gross examination, histology, histomorphometry, immunohistochemistry, and micro-computed tomography (µCT) analysis of the trabecular bone beneath the defect.
Results: Defects treated with MSC-EVs had more bone in the cartilage defect area than the PBS-treated defects (7.9% vs. 1.5%, p = 0.02). Less than one percent of the repair tissue in both groups was hyaline cartilage. ICRS II histological scoring showed that defects treated with MSC-EVs scored lower on “matrix staining” (20.8 vs. 50.0, p = 0.03), “cell morphology” (35.4 vs. 53.8, p = 0.04), and “overall assessment” (30.8 vs. 52.9, p = 0.03). Consistently, defects treated with MSC-EVs had lower collagen II and higher collagen I areal deposition. Defects treated with MSC-EVs had subchondral bone with significantly higher tissue mineral densities than PBS-treated defects (860 mg HA/cm3 vs. 838 mg HA/cm3, p = 0.02).
Interpretation / Conclusion: Intra-articular injections of MSC-EVs in conjunction with BMS led to osseous ingrowth that impaired optimal cartilage repair, while enhancing subchondral bone healing.
Orthopedic Research Laboratory, Aarhus University Hospital; Orthopedic Research Laboratory, Aarhus University Hospital; Orthopedic Research Laboratory, Aarhus University Hospital; Department of Biomedicine, Aarhus University; Orthopedic Research Laboratory, Aarhus University Hospital; Faculty of Dentistry, National University of Singapore AND Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research; Sports Trauma Clinic, Aarhus University Hospital
Background: Recently several bone marrow stimulation enhancement treatments have been developed to improve the cartilage repair after bone marrow stimulation.
Aim: The aim of the study was to evaluate the effects of mesenchymal stem cell- extracellular vesicles (MSC-EVs) on chondrocyte proliferation in vitro and on cartilage repair in vivo following bone marrow stimulation (BMS) of focal chondral defects of the knee.
Materials and Methods: Six adult Göttingen minipigs received two chondral defects in each knee. The pigs were randomized to treatment with either BMS combined with MSC-EVs or BMS combined with phosphate-buffered saline (PBS). Intra-articular injections MSC-EVs or PBS were performed immediately after closure of the surgical incisions, and at 2 and 4 weeks post-operatively. Repair was evaluated after 6 months with gross examination, histology, histomorphometry, immunohistochemistry, and micro-computed tomography (µCT) analysis of the trabecular bone beneath the defect.
Results: Defects treated with MSC-EVs had more bone in the cartilage defect area than the PBS-treated defects (7.9% vs. 1.5%, p = 0.02). Less than one percent of the repair tissue in both groups was hyaline cartilage. ICRS II histological scoring showed that defects treated with MSC-EVs scored lower on “matrix staining” (20.8 vs. 50.0, p = 0.03), “cell morphology” (35.4 vs. 53.8, p = 0.04), and “overall assessment” (30.8 vs. 52.9, p = 0.03). Consistently, defects treated with MSC-EVs had lower collagen II and higher collagen I areal deposition. Defects treated with MSC-EVs had subchondral bone with significantly higher tissue mineral densities than PBS-treated defects (860 mg HA/cm3 vs. 838 mg HA/cm3, p = 0.02).
Interpretation / Conclusion: Intra-articular injections of MSC-EVs in conjunction with BMS led to osseous ingrowth that impaired optimal cartilage repair, while enhancing subchondral bone healing.