Session 18: Experimental
Fredag den 25. oktober
13:30 - 15:00
Lokale: Vingsal 3
Chairmen: Casper Foldager og Mats Bue
148. Combination treatment of Spondylodiscitis with Moxifloxacin and Rifampicin may result in Reduced Vertebral Bone Concentrations of Moxifloxacin
Josefine Slater, Mathias A.F Bendtsen, Mats Bue, Pelle Hanberg, Nis P. Jørgensen, Andrea R. Jørgensen, Maiken Stilling, Kjeld Søballe
Orthopaedic Research Unit, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Horsens Regional Hospital; Deparment of Infectious Diseases, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital
Background: Spondylodiscitis (SD) is a devasting disease and approximately 30% of cases occurs following spinal surgery. Moxifloxacin (M) is used in the treatment of pyogenic SD, and for implant- associated infections caused by Staphylococci, M may be combined with rifampicin (R). However, studies have shown that R may reduce the plasma concentrations of M, which stresses the need for pharmacokinetic studies investigating this potential interaction in relevant tissues.
Purpose / Aim of Study: To evaluate vertebral bone (VB), intervertebral disc (IVD) and subcutaneous tissue (SCT) pharmacokinetics of M with and without R using microdialysis in a porcine model.
Materials and Methods: 16 female pigs were randomized into two groups: Group A received M 400 mg orally once daily, and Group B received M 400 mg orally combined with R 450 mg twice daily. For both groups, treatment was administered until steady-state was achieved. Following, measurements were obtained from plasma, VB, IVD and SCT for 24 hours. Microdialysis was applied for sampling in solid tissues and concentrations were quantified using LCMSMS.
Findings / Results: The following data are preliminary, but the complete analysis will be finalized prior to the conference. Both the area under the concentration curve (AUC) and the maximal concentration (Cmax) was significantly lower for Group B compared to Group A in VB and SCT (evaluated by mann-whitney U test, p<0.05). Ranging from 1,13 to 1,51, tissue penetration (AUCtissue/AUCplasma) in Group A was complete in all compartments (full data set not yet obtained for group B). For both groups, tissue concentrations were stable throughout the sampling period, indicating that steady-state was achieved.
Conclusions: Group B exhibited lower AUC and Cmax values in VB and SCT, which indicates that the combination of M and R reduces the spine tissue concentrations compared to when M is administered as a monotherapy. The possible clinical implications of this will subsequently be discussed in the following work.
Orthopaedic Research Unit, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Horsens Regional Hospital; Deparment of Infectious Diseases, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital
Background: Spondylodiscitis (SD) is a devasting disease and approximately 30% of cases occurs following spinal surgery. Moxifloxacin (M) is used in the treatment of pyogenic SD, and for implant- associated infections caused by Staphylococci, M may be combined with rifampicin (R). However, studies have shown that R may reduce the plasma concentrations of M, which stresses the need for pharmacokinetic studies investigating this potential interaction in relevant tissues.
Purpose / Aim of Study: To evaluate vertebral bone (VB), intervertebral disc (IVD) and subcutaneous tissue (SCT) pharmacokinetics of M with and without R using microdialysis in a porcine model.
Materials and Methods: 16 female pigs were randomized into two groups: Group A received M 400 mg orally once daily, and Group B received M 400 mg orally combined with R 450 mg twice daily. For both groups, treatment was administered until steady-state was achieved. Following, measurements were obtained from plasma, VB, IVD and SCT for 24 hours. Microdialysis was applied for sampling in solid tissues and concentrations were quantified using LCMSMS.
Findings / Results: The following data are preliminary, but the complete analysis will be finalized prior to the conference. Both the area under the concentration curve (AUC) and the maximal concentration (Cmax) was significantly lower for Group B compared to Group A in VB and SCT (evaluated by mann-whitney U test, p<0.05). Ranging from 1,13 to 1,51, tissue penetration (AUCtissue/AUCplasma) in Group A was complete in all compartments (full data set not yet obtained for group B). For both groups, tissue concentrations were stable throughout the sampling period, indicating that steady-state was achieved.
Conclusions: Group B exhibited lower AUC and Cmax values in VB and SCT, which indicates that the combination of M and R reduces the spine tissue concentrations compared to when M is administered as a monotherapy. The possible clinical implications of this will subsequently be discussed in the following work.
149. Pharmacokinetics of double-dose cefuroxime in porcine intervertebral disc and vertebral cancellous bone – a randomized microdialysis study
Pelle Hanberg, Andrea René Jørgensen, Maiken Stilling, Maja Thomassen, Kjeld Søballe, Mats Bue
Department of Orthopaedic Surgery, Horsens Regional Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Orthopaedic Surgery, Horsens Regional Hospital
Background: Cefuroxime is a time-dependent antibiotic widely used as perioperative prophylaxis in spine surgery. A previous study has indicated that a single dose of cefuroxime provided insufficient spine tissue concentrations for spine procedures lasting more than 2-3 hours.
Purpose / Aim of Study: To evaluate if a twofold increase of standard dosage of 1.5g cefuroxime given as one double dose or two single doses with 4- hours intervals will lead to sufficient cefuroxime spine tissue concentrations throughout the dosing interval.
Materials and Methods: This is preliminary data for 8 out of 16 pigs. Data from all 16 pigs will be included for the conference. Eight pigs were randomized into two groups: Group A received one double dose of cefuroxime (3g) as a bolus, and Group B received two single doses of cefuroxime (2x1.5g) with 4-hours intervals. Measurements were obtained from plasma, subcutaneous tissue (SCT), vertebral cancellous bone and the intervertebral disc (IVD) for 8-hours thereafter. Microdialysis was applied for sampling in solid tissues. The cefuroxime concentrations were determined using UHPLC.
Findings / Results: The time with concentrations above the minimal inhibitory concentration (T>MIC) for the clinical breakpoint MIC for S aureus of 4 μg/ml, was superior in all compartments for Group B. For the MIC of 4 μg/ml, the mean T>MIC in all compartments ranged between 53-73% and 85-95% for Group A and B, respectively. Both groups exhibited comparable area under the concentration- curves (AUC) with the highest values found in plasma compared to the remaining compartments. The peak drug concentrations were lower for both vertebral cancellous bone and IVD compared to both SCT and plasma in both groups. When comparing the two groups, higher peak drug concentrations were found in all compartments for Group A. Tissue penetration was incomplete and delayed for all compartments.
Conclusions: Despite comparable pharmacokinetic results between the two groups, Group B exhibited superior T>MIC in all compartments for the clinical breakpoint MIC for S aureus of 4 μg/ml. Administration of cefuroxime as two single doses with 4- hours intervals provided sufficient cefuroxime spine tissue concentrations for a minimum of 85% of an 8-hour dosing interval.
Department of Orthopaedic Surgery, Horsens Regional Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Orthopaedic Surgery, Horsens Regional Hospital
Background: Cefuroxime is a time-dependent antibiotic widely used as perioperative prophylaxis in spine surgery. A previous study has indicated that a single dose of cefuroxime provided insufficient spine tissue concentrations for spine procedures lasting more than 2-3 hours.
Purpose / Aim of Study: To evaluate if a twofold increase of standard dosage of 1.5g cefuroxime given as one double dose or two single doses with 4- hours intervals will lead to sufficient cefuroxime spine tissue concentrations throughout the dosing interval.
Materials and Methods: This is preliminary data for 8 out of 16 pigs. Data from all 16 pigs will be included for the conference. Eight pigs were randomized into two groups: Group A received one double dose of cefuroxime (3g) as a bolus, and Group B received two single doses of cefuroxime (2x1.5g) with 4-hours intervals. Measurements were obtained from plasma, subcutaneous tissue (SCT), vertebral cancellous bone and the intervertebral disc (IVD) for 8-hours thereafter. Microdialysis was applied for sampling in solid tissues. The cefuroxime concentrations were determined using UHPLC.
Findings / Results: The time with concentrations above the minimal inhibitory concentration (T>MIC) for the clinical breakpoint MIC for S aureus of 4 μg/ml, was superior in all compartments for Group B. For the MIC of 4 μg/ml, the mean T>MIC in all compartments ranged between 53-73% and 85-95% for Group A and B, respectively. Both groups exhibited comparable area under the concentration- curves (AUC) with the highest values found in plasma compared to the remaining compartments. The peak drug concentrations were lower for both vertebral cancellous bone and IVD compared to both SCT and plasma in both groups. When comparing the two groups, higher peak drug concentrations were found in all compartments for Group A. Tissue penetration was incomplete and delayed for all compartments.
Conclusions: Despite comparable pharmacokinetic results between the two groups, Group B exhibited superior T>MIC in all compartments for the clinical breakpoint MIC for S aureus of 4 μg/ml. Administration of cefuroxime as two single doses with 4- hours intervals provided sufficient cefuroxime spine tissue concentrations for a minimum of 85% of an 8-hour dosing interval.
150. Adipocytes may have an important function for remodeling of the human myotendinous junction
Jens Rithamer Jakobsen, Niels Rithamer Jakobsen, Abigail Mackey, Michael Kjær, Michael Rindom Krogsgaard
Department of Sports Traumatology M51, Bispebjerg-Frederiksberg Hospital, Denmark; Department of Sports Traumatology M51, Bispebjerg-Frederiksberg Hospital, Denmark; Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Institute of Sports Medicine, Department of Orthopaedic Surgery M, , Bispebjerg-Frederiksberg Hospital, Denmark; Department of Sports Traumatology M51, Bispebjerg-Frederiksberg Hospital, Denmark
Background: The myotendinous junction (MTJ) is specialized in force transmission between muscle and tendon, and is an area where strain injuries frequently occur. Despite this, little is known about the human MTJ as most studies have been conducted on animals. The presence of adipocytes in skeletal muscle is normally observed in relation to injury and coupled to limited function in the muscle. However, in a pilot study we have observed that adipocytes are present also in healthy human MTJ. This has not been reported previously in neither human nor animal MTJ.
Purpose / Aim of Study: To analyze the presence of adipocytes at the human MTJ in healthy subjects as well as the effect of exercise on the presence of these cells. In addition, we want to investigate whether adipocytes are unique to the human MTJ or if they are also present in animal MTJ's.
Materials and Methods: From ten subjects, randomized to control or 4 weeks of heavy resistance training (HRT), we obtained samples from semitendinosus MTJ and stained immunohistochemically for adipocytes (PLIN1). The number of adipocytes adjacent to the MTJ was counted and the total length of MTJ with adjacent adipocytes was measured. In addition, samples from horse (N=15) and mice (N=9) MTJ were obtained and stained immunohistochemically.
Findings / Results: Adipocytes were present at the muscular side of the MTJ in all subjects. The median was 2.70 adipocytes pr. mm MTJ. There were large differences between subjects (Range: 6.94), but no difference observed between the two groups with either heavy resistance training or sedentary controls. Adipocytes were also present in MTJ from horse and mice .
Conclusions: Adipocytes are present in high concentration at the healthy human MTJ and was not affected by 4 weeks of HRT. The presence of adipocytes at the MTJ suggests that they have a function in this area, and we suggest that they are involved in the extensive remodeling process that occurs at the MTJ. The presence of adipocytes in human, horse and mice MTJ suggests that this phenomenon is not unique for the human MTJ.
Department of Sports Traumatology M51, Bispebjerg-Frederiksberg Hospital, Denmark; Department of Sports Traumatology M51, Bispebjerg-Frederiksberg Hospital, Denmark; Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Institute of Sports Medicine, Department of Orthopaedic Surgery M, , Bispebjerg-Frederiksberg Hospital, Denmark; Department of Sports Traumatology M51, Bispebjerg-Frederiksberg Hospital, Denmark
Background: The myotendinous junction (MTJ) is specialized in force transmission between muscle and tendon, and is an area where strain injuries frequently occur. Despite this, little is known about the human MTJ as most studies have been conducted on animals. The presence of adipocytes in skeletal muscle is normally observed in relation to injury and coupled to limited function in the muscle. However, in a pilot study we have observed that adipocytes are present also in healthy human MTJ. This has not been reported previously in neither human nor animal MTJ.
Purpose / Aim of Study: To analyze the presence of adipocytes at the human MTJ in healthy subjects as well as the effect of exercise on the presence of these cells. In addition, we want to investigate whether adipocytes are unique to the human MTJ or if they are also present in animal MTJ's.
Materials and Methods: From ten subjects, randomized to control or 4 weeks of heavy resistance training (HRT), we obtained samples from semitendinosus MTJ and stained immunohistochemically for adipocytes (PLIN1). The number of adipocytes adjacent to the MTJ was counted and the total length of MTJ with adjacent adipocytes was measured. In addition, samples from horse (N=15) and mice (N=9) MTJ were obtained and stained immunohistochemically.
Findings / Results: Adipocytes were present at the muscular side of the MTJ in all subjects. The median was 2.70 adipocytes pr. mm MTJ. There were large differences between subjects (Range: 6.94), but no difference observed between the two groups with either heavy resistance training or sedentary controls. Adipocytes were also present in MTJ from horse and mice .
Conclusions: Adipocytes are present in high concentration at the healthy human MTJ and was not affected by 4 weeks of HRT. The presence of adipocytes at the MTJ suggests that they have a function in this area, and we suggest that they are involved in the extensive remodeling process that occurs at the MTJ. The presence of adipocytes in human, horse and mice MTJ suggests that this phenomenon is not unique for the human MTJ.
151. Protective Paracrine Effect on Chondrocytes when Co-cultured with Mesenchymal Stem Cells in a Hyaluronic Acid Hydrogel in vitro
Mogensen Simon Linbrecht, Rasmussen Martin Krøyer, Foldager Casper Bindzus
Orthopaedic Research Lab, Aarhus University Hospital; Department of Food Science, Aarhus University; Orthopaedic Research Lab, Aarhus University Hospital
Background: Osteoarthritis (OA) is an inflammatory degenerative disease causing irreversible damage to the articular cartilage. Mesenchymal stem cells (MSCs) have been shown to affect host cells by paracrine stimulation in regenerative environments.
Purpose / Aim of Study: The aim of the present study was to investigate cell viability and paracrine effects of MSCs on human chondrocytes in an inflammatory co-culture assay. We hypothesized that MSCs immobilized in a hyaluronic acid (HA) hydrogel exerted protective paracrine effects on human chondrocytes when exposed to interleukin- 1beta (IL-1b).
Materials and Methods: Non-osteoarthritic human chondrocytes where co-cultured in biphasic wells with human MSCs immobilized in a divinyl sulfone crosslinked HA (500- 749 KDa) hydrogel (HyA) without physical contact between the two cell types. We investigated the chondrocyte response in an IL-1b induced inflammatory environment in four groups: 1) chondrocytes 2) chondrocytes and HyA 3) chondrocytes and MSCs 4) chondrocytes and HyA-immobilized MSCs. Follow-up times were day 3, 7 ,14, and 28. Relative gene expressions of aggrecan, SOX9, MMP-13 and ADAMTS-5 were measured. The unfolded protein response (UPR) was examined as a surrogate marker of cellular stress and the viability was studied using Hoechst staining.
Findings / Results: MSC viability was maintained in the hydrogel for up to 28 days. In chondrocytes co-cultured with MSCs or MSCs immobilized in HyA we found significant up- regulation of SOX9 at day 7, 14 and 28 and a significant down-regulation of ADAMTS-5 at day 14 and 28 compared with controls and HyA alone (p < 0.05). The UPR was down-regulated (1-3 fold) in co-cultures with MSCs but results were not significant.
Conclusions: We show that human MSCs can be immobilized in HyA and survive for up to 28 days and that MSCs with or without HyA exert protective paracrine effect on non- osteoarthritic human chondrocytes in an IL1-b induced.
Orthopaedic Research Lab, Aarhus University Hospital; Department of Food Science, Aarhus University; Orthopaedic Research Lab, Aarhus University Hospital
Background: Osteoarthritis (OA) is an inflammatory degenerative disease causing irreversible damage to the articular cartilage. Mesenchymal stem cells (MSCs) have been shown to affect host cells by paracrine stimulation in regenerative environments.
Purpose / Aim of Study: The aim of the present study was to investigate cell viability and paracrine effects of MSCs on human chondrocytes in an inflammatory co-culture assay. We hypothesized that MSCs immobilized in a hyaluronic acid (HA) hydrogel exerted protective paracrine effects on human chondrocytes when exposed to interleukin- 1beta (IL-1b).
Materials and Methods: Non-osteoarthritic human chondrocytes where co-cultured in biphasic wells with human MSCs immobilized in a divinyl sulfone crosslinked HA (500- 749 KDa) hydrogel (HyA) without physical contact between the two cell types. We investigated the chondrocyte response in an IL-1b induced inflammatory environment in four groups: 1) chondrocytes 2) chondrocytes and HyA 3) chondrocytes and MSCs 4) chondrocytes and HyA-immobilized MSCs. Follow-up times were day 3, 7 ,14, and 28. Relative gene expressions of aggrecan, SOX9, MMP-13 and ADAMTS-5 were measured. The unfolded protein response (UPR) was examined as a surrogate marker of cellular stress and the viability was studied using Hoechst staining.
Findings / Results: MSC viability was maintained in the hydrogel for up to 28 days. In chondrocytes co-cultured with MSCs or MSCs immobilized in HyA we found significant up- regulation of SOX9 at day 7, 14 and 28 and a significant down-regulation of ADAMTS-5 at day 14 and 28 compared with controls and HyA alone (p < 0.05). The UPR was down-regulated (1-3 fold) in co-cultures with MSCs but results were not significant.
Conclusions: We show that human MSCs can be immobilized in HyA and survive for up to 28 days and that MSCs with or without HyA exert protective paracrine effect on non- osteoarthritic human chondrocytes in an IL1-b induced.
152. Continuous wireless force measurement in gradual and acute bone lengthening
Markus Frost, Tariq Rahman , William Mackenzie, Harald Steen, Søren Kold
Orthopaedic Department, Aalborg University Hospital; Hospital for Children, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA; Hospital for Children, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA; Orthopaedic Division, Oslo University Hospital; Orthopaedic Department, Aalborg University Hospital
Background: Limb lengthening might result in reduced joint movement and risk of joint subluxation due to high resisting forces of lengthened soft tissues. At present, soft tissue forces are only assessed indirectly by clinical examination.
Purpose / Aim of Study: We aimed to develop and test instrumentation for continuous wireless force measurements in a rabbit limb lengthening model. We tested whether the equipment could detect differences in generated forces between gradual and acute limb lengthening.
Materials and Methods: In a paired controlled study, five New Zealand white rabbits underwent 12 mm gradual limb lengthening of the left leg and 12 mm acute limb lengthening of the right leg. GRADUAL LENGTHENING PROTOCOL: A midshaft osteotomy was performed on the left tibia. An external fixator with a built-in strain gauge for force measurement was attached to the bone by Orthofix pins. Lengthening was initiated from the third postoperative day with 0.25 mm two times per day for 24 days. The force was measured by the strain gauge at 15 sec. intervals and wirelessly transmitted to a computer. The bone formation was monitored 3 times a week by x-ray. At day 28 the rabbits were anaesthetized, and prior to euthanization, the right leg was acute lengthened. ACTUTE LENGTHENING PROTOCOL: Right leg was prepared as left and acute lengthening was performed in steps of 0.25 mm allowing for two measurements prior to next lengthening. The paired differences in force between acute and gradual lengthening were compared with a Wilcoxon signed- rank test.
Findings / Results: The median (interquartile range) maximum resting force was 5.5 (5.1-6.7) N/kg of rabbit during gradual bone lengthening and 25.2 (24.1-26.2) N/kg during acute lengthening. The median paired difference between acute and gradual lengthening was 18.4 (17.9-18.5) N/kg (p=0.04). Postoperative micro-CT demonstrated bone formation in the limbs with gradual bone lengthening.
Conclusions: The new device for wireless monitoring of force during limb lengthening was capable of detecting a difference between gradual and acute limb lengthening in a rabbit model. The generated force was substantially higher in acute compared with gradual lengthening despite bone formation occurring in the gradually lengthened tibias.
Orthopaedic Department, Aalborg University Hospital; Hospital for Children, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA; Hospital for Children, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA; Orthopaedic Division, Oslo University Hospital; Orthopaedic Department, Aalborg University Hospital
Background: Limb lengthening might result in reduced joint movement and risk of joint subluxation due to high resisting forces of lengthened soft tissues. At present, soft tissue forces are only assessed indirectly by clinical examination.
Purpose / Aim of Study: We aimed to develop and test instrumentation for continuous wireless force measurements in a rabbit limb lengthening model. We tested whether the equipment could detect differences in generated forces between gradual and acute limb lengthening.
Materials and Methods: In a paired controlled study, five New Zealand white rabbits underwent 12 mm gradual limb lengthening of the left leg and 12 mm acute limb lengthening of the right leg. GRADUAL LENGTHENING PROTOCOL: A midshaft osteotomy was performed on the left tibia. An external fixator with a built-in strain gauge for force measurement was attached to the bone by Orthofix pins. Lengthening was initiated from the third postoperative day with 0.25 mm two times per day for 24 days. The force was measured by the strain gauge at 15 sec. intervals and wirelessly transmitted to a computer. The bone formation was monitored 3 times a week by x-ray. At day 28 the rabbits were anaesthetized, and prior to euthanization, the right leg was acute lengthened. ACTUTE LENGTHENING PROTOCOL: Right leg was prepared as left and acute lengthening was performed in steps of 0.25 mm allowing for two measurements prior to next lengthening. The paired differences in force between acute and gradual lengthening were compared with a Wilcoxon signed- rank test.
Findings / Results: The median (interquartile range) maximum resting force was 5.5 (5.1-6.7) N/kg of rabbit during gradual bone lengthening and 25.2 (24.1-26.2) N/kg during acute lengthening. The median paired difference between acute and gradual lengthening was 18.4 (17.9-18.5) N/kg (p=0.04). Postoperative micro-CT demonstrated bone formation in the limbs with gradual bone lengthening.
Conclusions: The new device for wireless monitoring of force during limb lengthening was capable of detecting a difference between gradual and acute limb lengthening in a rabbit model. The generated force was substantially higher in acute compared with gradual lengthening despite bone formation occurring in the gradually lengthened tibias.
153. Local vancomycin concentrations after intra-articular injection into the knee joint – an experimental porcine study
Mats Bue, Maja B Thomassen, Ole H Larsen, Andrea R Jørgensen, Maiken Stilling, Kjeld Søballe, Pelle Hanberg
Orthopaedic Surgery, Horsens Regional Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Clinical Medicine, Aarhus University; Orthopaedic Research Unit, Aarhus University Hospital; Orthopaedic Surgery, Aarhus University Hospital; Orthopaedic Surgery, Aarhus University Hospital; Orthopaedic Surgery, Horsens Regional Hospital
Background: Intra-articular injection of vancomycin may be an important antimicrobial prophylactic supplement to systemic administration in the prevention of joint infection after reconstructive or prosthetic surgery.
Purpose / Aim of Study: To investigate the prophylactic effectiveness of an intra-articular injection of vancomycin into the knee joint.
Materials and Methods: In 8 female pigs, 500 mg diluted vancomycin was given by intra-articular injection into the knee joint. Microdialysis was used for dense sampling of vancomycin concentrations over 12 hours in the synovial fluid of the knee joint, and in the adjacent femoral and tibial cancellous bone and subcutaneous tissue. Venous blood samples were obtained as reference.
Findings / Results: The mean (SD) peak drug concentration of vancomycin in the synovial fluid of the knee joint was 5,277 (5,668) μg/ml. Only one pig failed to reach a peak drug concentration above 1,000 μg/ml. The concentration remained high throughout the sampling interval with a mean (SD) concentration of 337 (259) μg/ml after 690 min. For all extraarticular compartments, the pharmacokinetic parameters (area under the concentration time-curve, peak drug concentration, and time to peak drug concentration) were comparable. The highest extraarticular mean (SD) peak drug concentration of 4.4 (2.3) μg/ml was found in subcutaneous tissue.
Conclusions: An intra-articular injection of 500 mg diluted vancomycin was found to provide significant prophylactic mean concentrations for at least 12 hours in the synovial fluid of the knee joint. Correspondingly, the adjacent tissue and plasma concentrations were low, but remained stable, signifying low risk of systemic toxic side effects and a slow release or uptake from the synovium to the systemic circulation.
Orthopaedic Surgery, Horsens Regional Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Clinical Medicine, Aarhus University; Orthopaedic Research Unit, Aarhus University Hospital; Orthopaedic Surgery, Aarhus University Hospital; Orthopaedic Surgery, Aarhus University Hospital; Orthopaedic Surgery, Horsens Regional Hospital
Background: Intra-articular injection of vancomycin may be an important antimicrobial prophylactic supplement to systemic administration in the prevention of joint infection after reconstructive or prosthetic surgery.
Purpose / Aim of Study: To investigate the prophylactic effectiveness of an intra-articular injection of vancomycin into the knee joint.
Materials and Methods: In 8 female pigs, 500 mg diluted vancomycin was given by intra-articular injection into the knee joint. Microdialysis was used for dense sampling of vancomycin concentrations over 12 hours in the synovial fluid of the knee joint, and in the adjacent femoral and tibial cancellous bone and subcutaneous tissue. Venous blood samples were obtained as reference.
Findings / Results: The mean (SD) peak drug concentration of vancomycin in the synovial fluid of the knee joint was 5,277 (5,668) μg/ml. Only one pig failed to reach a peak drug concentration above 1,000 μg/ml. The concentration remained high throughout the sampling interval with a mean (SD) concentration of 337 (259) μg/ml after 690 min. For all extraarticular compartments, the pharmacokinetic parameters (area under the concentration time-curve, peak drug concentration, and time to peak drug concentration) were comparable. The highest extraarticular mean (SD) peak drug concentration of 4.4 (2.3) μg/ml was found in subcutaneous tissue.
Conclusions: An intra-articular injection of 500 mg diluted vancomycin was found to provide significant prophylactic mean concentrations for at least 12 hours in the synovial fluid of the knee joint. Correspondingly, the adjacent tissue and plasma concentrations were low, but remained stable, signifying low risk of systemic toxic side effects and a slow release or uptake from the synovium to the systemic circulation.
155. Cognitive load in virtual reality simulation of hip fracture surgery: an investigation of different methods to estimate cognitive load.
Jeppe Kempf Nørskov, Jan Duedal Rölfing, Charlotte Paltved, Lars Konge, Andersen Steven Arild Wuyts
MidtSim, Aarhus Universitetshospital Skejby; Institut for Klinisk Medicin, Aarhus Universitet; MidtSim , Aarhus Universitetshospital Skejby; CAMES, Københavns Universitet; CAMES, Københavns Universitet
Background: One out of 10 hip fracture patients dies within the first months and approximately one out of four within the first year. High quality surgical training is therefore paramount for the young surgeon. Virtual reality (VR) simulation training has been introduced to address this issue, and previous studies have demonstrated that VR simulation training can ensure basic proficiency of the junior surgeon. Cognitive load (CL) theory has become an accepted theoretical framework for evaluation of medical education. Conflicting reports exist regarding the correlation of the different methods for CL estimation. We therefore set out to investigate these methods further.
Purpose / Aim of Study: The aim of this study was to investigate the relationship between performance in VR simulation tests in a hip fracture surgical training program and CL estimated by secondary-task reaction time test and the NASA-TLX and PAAS questionnaires. We further also investigated the relationship between the different CL measurement methods.
Materials and Methods: Participants were 42 first-year orthopedic residents employed at departments in the Central- or the North Denmark Region.The study was carried out at a central simulation center from November 2016 to March 2019. Performance was measured as passing/failing a procedure and the number of failed procedures within the latest three and five simulations. CL was measured by reaction time testing during simulation and using the NASA-TLX and PAAS questionnaires.
Findings / Results: We found that passing simulation tests were associated with a lower CL than failed for both the reaction time and questionnaire estimates of CL. The questionnaire responses were further affected by the number of failed procedures during last three and five procedures, resulting in a higher number of failures being associated with higher CL.
Conclusions: Questionnaires for estimation of CL seemed to be affected by participant frustration after failing a simulation – a meta-cognitive "carry over”-effect. This could be a general limitation of the subjective questionnaire approach to estimate CL. Reducing CL through instructional design and handling of participant frustration might improve the learning outcome of simulation training programs.
MidtSim, Aarhus Universitetshospital Skejby; Institut for Klinisk Medicin, Aarhus Universitet; MidtSim , Aarhus Universitetshospital Skejby; CAMES, Københavns Universitet; CAMES, Københavns Universitet
Background: One out of 10 hip fracture patients dies within the first months and approximately one out of four within the first year. High quality surgical training is therefore paramount for the young surgeon. Virtual reality (VR) simulation training has been introduced to address this issue, and previous studies have demonstrated that VR simulation training can ensure basic proficiency of the junior surgeon. Cognitive load (CL) theory has become an accepted theoretical framework for evaluation of medical education. Conflicting reports exist regarding the correlation of the different methods for CL estimation. We therefore set out to investigate these methods further.
Purpose / Aim of Study: The aim of this study was to investigate the relationship between performance in VR simulation tests in a hip fracture surgical training program and CL estimated by secondary-task reaction time test and the NASA-TLX and PAAS questionnaires. We further also investigated the relationship between the different CL measurement methods.
Materials and Methods: Participants were 42 first-year orthopedic residents employed at departments in the Central- or the North Denmark Region.The study was carried out at a central simulation center from November 2016 to March 2019. Performance was measured as passing/failing a procedure and the number of failed procedures within the latest three and five simulations. CL was measured by reaction time testing during simulation and using the NASA-TLX and PAAS questionnaires.
Findings / Results: We found that passing simulation tests were associated with a lower CL than failed for both the reaction time and questionnaire estimates of CL. The questionnaire responses were further affected by the number of failed procedures during last three and five procedures, resulting in a higher number of failures being associated with higher CL.
Conclusions: Questionnaires for estimation of CL seemed to be affected by participant frustration after failing a simulation – a meta-cognitive "carry over”-effect. This could be a general limitation of the subjective questionnaire approach to estimate CL. Reducing CL through instructional design and handling of participant frustration might improve the learning outcome of simulation training programs.
156. Blood flow restricted low-load resistance strength training in patients with a variety of orthopedic lower limb injuries: a feasibility study
Stian Langgård Jørgensen, Marie Bagger Bohn
Department of Physio and Occupational Therapy, Horsens Regional Hospital; Department of orthopedic surgery, Horsens Regional Hospital
Background: Resistance training with low loads (~30% 1repetition maximum) performed with concurrent partial blood flow restriction of the working limb (Blood flow restricted exercise: LL- BFRE) has achieved scientific merit over the past decades. Further, LL- BFRE has demonstrated to promote gains in skeletal muscle hypertrophy and strength as comparable to that seen with heavy resistance strength (HRST). In some patients, however, HRST can be contraindicated due to pain or post surgical restrictions. Despite these contraindication, the majority of patients would most likely benefit from increasing (or at least maintaining) their skeletal muscle mass and strength in order to maintain a sufficiently high functional capacity level and quality of life.
Purpose / Aim of Study: To examine the feasibility of blood flow restricted low- load exercise (LL- BFRE) in patients suffering from orthopedic lower limb (LL) injuries and measure outcomes on muscle strength, functional capacity, jump height, and patient-reported outcome measures (PROM).
Materials and Methods: 14 patients (52 +/-17 years) diagnosed with variuos orthopedic lower limb injuries were included. The patients performed LL-BFRE for 4-8 weeks. LL-BFRE comprised of unilateral leg press with concurrent partial blood restriction (40% occlusion pressure) at 30%1RM. Two protocols were tested containing 4 rounds with 30-sec rest pauses. Participants completed 3 functional performance tests, 2 strength-based tests, 1 hop- test, and KOOS.
Findings / Results: Three patients dropped out due to exercise-related adverse events (2) and personal reasons (1). Thigh Circumferences and Isometric Knee Extensor Strength (injured side) increased from 45.2 ± 3.1 cm to 46.0 ± 4.0 cm (p=0.05) and 3.1 ± 0.8 N/m to 4.3 ± 1.4 N/m (p=0.01). 30-seconds sit to stand improved from 16 ± 7 repetitions to 19 ± 10 repetitions (p=0.02). KOOS Pain, Symptoms and Sport & Rec improved from 62 ± 19 points to 74 ± 20 point (p=0.03), 58 ± 16 points to 67 ± 15 points (p=0.03), and 22 ± 18 points to 40 ± 24 points (p=0.03).
Conclusions: LL-BFRE was feasible in patients suffering from different LL-injuries. The intervention may improve isometric strength, functional performance, and various PROMs
Department of Physio and Occupational Therapy, Horsens Regional Hospital; Department of orthopedic surgery, Horsens Regional Hospital
Background: Resistance training with low loads (~30% 1repetition maximum) performed with concurrent partial blood flow restriction of the working limb (Blood flow restricted exercise: LL- BFRE) has achieved scientific merit over the past decades. Further, LL- BFRE has demonstrated to promote gains in skeletal muscle hypertrophy and strength as comparable to that seen with heavy resistance strength (HRST). In some patients, however, HRST can be contraindicated due to pain or post surgical restrictions. Despite these contraindication, the majority of patients would most likely benefit from increasing (or at least maintaining) their skeletal muscle mass and strength in order to maintain a sufficiently high functional capacity level and quality of life.
Purpose / Aim of Study: To examine the feasibility of blood flow restricted low- load exercise (LL- BFRE) in patients suffering from orthopedic lower limb (LL) injuries and measure outcomes on muscle strength, functional capacity, jump height, and patient-reported outcome measures (PROM).
Materials and Methods: 14 patients (52 +/-17 years) diagnosed with variuos orthopedic lower limb injuries were included. The patients performed LL-BFRE for 4-8 weeks. LL-BFRE comprised of unilateral leg press with concurrent partial blood restriction (40% occlusion pressure) at 30%1RM. Two protocols were tested containing 4 rounds with 30-sec rest pauses. Participants completed 3 functional performance tests, 2 strength-based tests, 1 hop- test, and KOOS.
Findings / Results: Three patients dropped out due to exercise-related adverse events (2) and personal reasons (1). Thigh Circumferences and Isometric Knee Extensor Strength (injured side) increased from 45.2 ± 3.1 cm to 46.0 ± 4.0 cm (p=0.05) and 3.1 ± 0.8 N/m to 4.3 ± 1.4 N/m (p=0.01). 30-seconds sit to stand improved from 16 ± 7 repetitions to 19 ± 10 repetitions (p=0.02). KOOS Pain, Symptoms and Sport & Rec improved from 62 ± 19 points to 74 ± 20 point (p=0.03), 58 ± 16 points to 67 ± 15 points (p=0.03), and 22 ± 18 points to 40 ± 24 points (p=0.03).
Conclusions: LL-BFRE was feasible in patients suffering from different LL-injuries. The intervention may improve isometric strength, functional performance, and various PROMs