Session 15: Experimental/Infections

Fredag d. 27. oktober
13:00-14:30
Lokale: Reykjavik
Chairmen: Casper Foldager og Jeppe Lange

128. Composite Biomaterial as a Carrier for Bone Active Substances for Metaphyseal Tibial Bone Defect Reconstruction in Rats
Peter Frederik Horstmann, Bushan Raina Raina, Hanna Isaksson, Werner Hettwer, Lars Lidgren, Michael Mørk Petersen, Magnus Tägil
Department of Orthopedics, University of Copenhagen, Rigshospitalet; Department of Orthopedics, Clinical Sciences, Lund University; Department of Biomedical Engineering, Lund University; Department of Orthopedics, University of Copenhagen, Rigshospitalet; Department of Orthopedics, Clinical Sciences, Lund University; Department of Orthopedics, University of Copenhagen, Rigshospitalet; Department of Orthopedics, Clinical Sciences, Lund University


Background: Method of choice for reconstruction of cavitary bone defects after curettage of bone lesions, such as giant cell tumors of bone (GCT), remain controversial. Local zoledronic acid (ZA) has shown promising results as a local adjuvant in the treatment of GCT.
Purpose / Aim of Study: To investigate if a composite biomaterial (CBM) can be used for delivery of ZA, and bone morphogenic protein 2 (BMP-2).
Materials and Methods: 50 Sprague-Dawley rats were allocated to one of five groups (n=10/group) according to treatment of a 3- mm unicortical metaphyseal defect in the proximal tibia: 1) Empty defect; 2) Bone allograft; 3) CBM (CERAMENT™|G, BONESUPPORT AB); 4) CBM and ZA; 5) CBM, ZA and BMP-2. At 4-weeks, in-vivo micro-CT imaging was performed. At 8-weeks, all animals were examined with ex-vivo micro-CT, DXA, and histology.
Findings / Results: In-vivo micro-CT images at 4-weeks showed significantly higher mineralized volume (MV) in the defect in all CBM-treated groups. Ex-vivo micro-CT and DXA at 8-weeks showed that addition of ZA, even without BMP-2, increased MV, although the highest MV was seen in the BMP-2-treated group. Qualitative histological analysis found normal cortical bone architecture in the empty and the allograft groups, without convincing signs of trabecular bone formation inside the defect area. Trabecular bone and remnants of CBM were seen inside the original defect in all CBM-treated groups. The addition of ZA increased cortical thickness, and addition of BMP-2 further increased callus size with a visible callus extending beyond the margins of the old cortex.
Conclusions: The biomaterial used in our study can carry anabolic (BMP-2) and anti-catabolic (ZA) agents, which appears to significantly enhance bone mineralization beyond mere physical defect filling.

129. Risk of revision, prosthetic joint infection and death following total hip or total knee arthroplasty in patients with rheumatoid arthritis – a nationwide cohort study from Denmark
René Cordtz, Pil Højgaard, Lars Erik Kristensen, Søren Overgaard, Anders Odgaard, Hanne Lindegaard, Lene Dreyer
Department of Rheumatology, Gentofte Hospital, Center for Rheumatology and Spine Diseases, Rigshospitalet; The Parker Institute, Bispebjerg and Frederiksberg Hospital; The Parker Institute, Bispebjerg and Frederiksberg Hospital; Department of Orthopaedic Surgery and Traumatology, Odense University Hospital; Department of Orthopaedic Surgery, Copenhagen University Hospital Herlev-Gentofte; Department of Rheumatology, Odense University Hospital; Department of Rheumatology, Gentofte Hospital, Center for Rheumatology and Spine Diseases, Rigshospitalet


Background: Previous studies have implied that rheumatoid arthritis (RA) patients are at increased risk of prosthetic joint infection (PJI) but not death following total hip and total knee arthroplasty (THA and TKA, respectively). Biological disease modifying anti-rheumatic drugs (bDMARDs) can halt the development of joint erosions in RA, but it is unknown if they affect risks of revision, PJI and death.
Purpose / Aim of Study: To investigate risk of revision (10-year), PJI (1-year) and death (1-year) following THA/TKA in 1) RA compared with osteoarthritis (OA) patients; and 2) bDMARD compared with non-bDMARD treated RA patients.
Materials and Methods: To investigate risk of revision (10-year), PJI (1-year) and death (1-year) following THA/TKA in 1) RA compared with osteoarthritis (OA) patients; and 2) bDMARD compared with non-bDMARD treated RA patients.
Findings / Results: We identified 3913 RA and 120,499 OA patients. RA patients had decreased SHR for revision (0.71; 95%CI 0.57-0.89), but increased SHR for PJI (1.84; 95%CI 1.55- 2.18) and HR for death (1.58; 95%CI 1.47- 1.69) compared with OA patients. In DANBIO, 345 of 1946 registered RA patients with THA/TKA received a bDMARD within 90 days before surgery. These patients did not have a statistically significant increased SHR for PJI (1.61; 95%CI 0.70-3.69) nor HR for death (0.75; 95%CI 0.24-2.33) compared with non- bDMARD treated.
Conclusions: We found an increased risk of PJI and death in RA compared with OA patients following THA/TKA. bDMARD exposure was not associated with statistically significant increased risks of PJI nor death; however, estimates were numerically increased and more studies are needed to confirm no excessive risk exists.

130. Microcalorimetric detection of staphylococcal biofilm growth on various prosthetic biomaterials after exposure to daptomycin
Christen Ravn, Inês Santos Ferreira, Elena Maiolo, Søren Overgaard, Andrej Trampuz
Orthopaedic Research Unit and Dep. of Orthopaedic Surgery, University of Southern Denmark and Odense University Hospital; Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Portugal; Center for Musculoskeletal Surgery, Charité - University Medicine Berlin, Berlin, Germany; Orthopaedic Research Unit and Dep. of Orthopaedic Surgery, University of Southern Denmark and Odense University Hospital; Center for Musculoskeletal Surgery, Charité - University Medicine Berlin, Berlin, Germany


Background: Prosthetic joint infection involves bacterial biofilm formation.
Purpose / Aim of Study: Primary aim of this in vitro study was to test the efficacy of daptomycin to eradicate staphylococcal biofilms on various orthopedic implant surfaces and materials. Secondary aim was to quantitatively estimate the formation of staphylococcal biofilm.
Materials and Methods: We tested six clinically important biomaterials: cobalt chrome alloy, pure titanium, grid-blasted titanium, porous plasma-coated titanium with/without hydroxyapatite, and polyethylene. Biofilms of S. aureus and S. epidermidis were formed on the samples and thereafter exposed to daptomycin. Samples were subsequently sonicated in order to detect dislodged biofilm bacteria and transferred to a microcalorimeter for real-time measurement of growth related heat flow. Minimal biofilm eradication concentration (MBEC) was determined as the lowest concentration (mg/L) of daptomycin required to eradicate the biofilm bacteria on the sample. The time (hours) to detection expressed as the heat flow >50 µW (TTD- 50) indirectly quantifies the initial amount of biofilm bacteria, with a shorter TTD-50 representing a larger amount of bacteria.
Findings / Results: Median MBEC of S. aureus biofilm on smooth metallic surfaces was significantly lower than the rough metallic surfaces. Variations of MBEC in experiments with S. epidermidis biofilms on test samples with smooth or rough surface was found non-significant. Mean TTD-50 of S. aureus biofilms on rough metallic samples was significantly lower than smooth metallic samples and polyethylene. Mean TTD-50 with S. epidermidis biofilm on smooth metals was also significantly higher than their rough counterparts.
Conclusions: Growth of biofilm bacteria on orthopedic materials are variably influenced by exposure to the potent antimicrobial effect of high-dose daptomycin.

131. Radiographic biodegradation patterns of a hydroxyapatite / calcium sulfate biocomposite. Results from a large animal bone defect model.
Werner Hettwer
Orthopaedic Surgery, Rigshospitalet


Background: Ceramic biomaterials can be used as bone graft substitutes for reconstruction of bone defects. However, post-operative imaging features are often unique and difficult to interpret, particularly without histological correlation.
Purpose / Aim of Study: The aim of this study was to establish a clinically relevant large animal bone defect model that allows further characterisation, analysis and correlation of imaging and histology findings.
Materials and Methods: Standardised bone defects (diameter 2.5cm, depth 2cm, volume approx. 10ml) were created in the medial femoral condyles of ten merino-wool sheep (age 2 -4 years). The defects were filled with a ceramic biomaterial (Cerament BVF or G), allograft or left empty for comparison. After the initial procedure on the right hind leg, an identical intervention was performed on the contralateral side 3 months later, so that a spectrum of differentially treated bone voids could be obtained by sacrifice at various time points post-implantation.
Findings / Results: We present our radiographic results after a follow-up of 12 months and describe a consistent pattern of radiographic signs of biodegradation of the implanted biomaterial which overlaps the simultaneously ongoing process of bone formation. We consistently observed a radio-dense area in the periphery of the lesion (“halo sign”) progressively migrating towards the spherical biocomposite remnant, located at centre of the treated defects (“marble sign”). Both signs became more and more indistinct from surrounding cancellous bone and progressively disappeared with time.
Conclusions: We have established a large animal model, which appears to reproduce comparable radiographic post- implantation features regularly observed in clinical cases. This model provides valuable information regarding conclusive interpretation of basic & advanced imaging features.

132. Characterization of the remodeling events contributing to trabecularization of cortical bone: A study on human fibula diaphysis
Christina M. Andreasen, Jesper S. Thomsen, Lydia P. Bakalova, Annemarie Brüel, Ellen M. Hauge, Gete E.T. Eschen, Birgitte J. Kiil, Jean-Marie Delaisse, Mariana E. Kersh, Thomas L. Andersen
Orthopaedic Surgery & Traumatology, Odense University Hospital; Biomedicine, Aarhus University; Mechanical Science & Engineering, University of Illinois at Urbana-Champaign, USA; Biomedicine, Aarhus University; Rheumatology, Aarhus University Hospital; Plastic Surgery, Aarhus University Hospital; Plastic Surgery, Aarhus University Hospital; Clinical Cell Biology, Vejle Hospital/Lillebaelt Hospital; Mechanical Science & Engineering, University of Illinois at Urbana-Champaign, USA; Clinical Cell Biology, Vejle Hospital/Lillebaelt Hospital


Background: The trabecularization of cortical bone leads to the fragilization of the bones in elderly.
Purpose / Aim of Study: To investigate the intracortical remodeling events contributing to this endosteal trabecularization.
Materials and Methods: Fibular diaphysis specimens from 19 patients (14 men, 5 women, 43–75 years) undergoing a jaw reconstruction. All specimens were plastic embedded, µCT scanned and sectioned along the scanning plan, making it possible to investigate the same canals analyzed in 3D by µCT and in 2D by histology.
Findings / Results: The 3D analysis showed a 3.5-fold higher porosity and canals with a 3-fold larger diameter at the endosteal half compared to the periosteal half. The 2D analysis of these canals as intracortical pores showed that large pores (>100 µm diameter) were 3.3-fold more frequent in the endosteal half than in the periosteal half. A histological characterization of 948 pores revealed that these enlarged pores are preferentially resorptive pores overlapping with the pore of a preexisting parent osteon showing no signs of bone formation. The odds of being such a resorptive pore were 1.6- fold higher in the endosteal half than in the periosteal half, and 6-fold higher in the enlarged pores (>100 µm diameter) than in the smaller pores. The enlarged resorptive pores often resulted in coalescence of two or more pores. The odds of finding these enlarged coalescent resorptive pores were 1.9- fold higher in the endosteal half than in the periosteal half, and 8-fold higher in the enlarged pores (>100 µm diameter) than in the smaller pores.
Conclusions: Both the 2D and 3D analyses showed that the cortical trabecularization may in part result from the accumulation of enlarged resorptive pores/canals in the endosteal part of cortex, suggesting that the bone formation is uncoupled from the bone resorption in these pores.

133. Regenerative tissue after matrix-associated cell implantation has better quality using amplified chondrocytes compared to synovial derived stem cells in a rabbit model
Hagen Schmal, Anke Bernstein, Michael Seidenstücker, Katharina Böttiger, Eva Johanna Kubosch
Department of Orthopaedics and Traumatology, Odense University Hospital; Department of Orthopedics and Trauma Surgery, Albert-Ludwigs University Medical Center Freiburg; Department of Orthopedics and Trauma Surgery, Albert-Ludwigs University Medical Center Freiburg; Department of Orthopedics and Trauma Surgery, Albert-Ludwigs University Medical Center Freiburg; Department of Orthopedics and Trauma Surgery, Albert-Ludwigs University Medical Center Freiburg


Background: The autologous chondrocyte implantation is an accepted method to treat cartilage lesions. However, known problems regarding donor site morbidity and the 2-step design make the search for cell alternatives ongoing.
Purpose / Aim of Study: Aim of the study was to test the potential of SMSC to regenerate cartilage using a matrix-associated implantation.
Materials and Methods: SMSC were able to form cartilage in- vitro. In an osteochondral defect model of the medial femoral condyle in rabbits, a collagen type I/III membrane was seeded with either amplified allogenic chondrocytes or SMSC and then transplanted into the lesion. A tailored piece synovial membrane served as a control. Besides macroscopic and histological evaluation, the regenerated tissue was examined biomechanically analyzing thickness, instant and shear modulus.
Findings / Results: The evaluation of the macroscopic degree of healing using the ICRS score and the area of healing did not show differences between the groups after 6 weeks. Moreover, the thickness of the regenerated tissue was higher in all intervention groups than in natural cartilage, but there was no difference between the groups. However, the instant and shear modulus, reflecting the biomechanical strength, was superior in the implantation group using chondrocytes. Histologically, the regenerated lesions after matrix- coupled chondrocyte implantation had a more chondrogenic structure and expressed more proteoglycans, which was reflected by a lower Pritzker Score compared to the controls. In the repair tissue of all groups the collagen types I, II, X were expressed without statistical differences.
Conclusions: Regenerated cartilage using undifferentiated SMSC for matrix- associated implantation in a defect model in rabbits did not show a comparable or higher quality than the current standard utilizing amplified chondrocytes.

134. Time spent on alcohol rub prior to surgery – Does time feel faster with increasing age?
Jakob Klit, Per Hviid Gundtoft, Eske Brand, Peter Toft Tengberg, Kristoffer Weisskirchner Barfod
, OMG - Orthopedic Myth Grinders; , OMG - Orthopedic Myth Grinders; , OMG - Orthopedic Myth Grinders; , OMG - Orthopedic Myth Grinders; , OMG - Orthopedic Myth Grinders


Background: Guidelines recommend pre-wash followed by antisepsis using alcohol rub for 120 sec. Senior surgeons seem to possess the ability to perform a full surgical hand antisepsis in no time while younger surgeons are left scrubbing and rubbing for infinity. Possibly due to a changed perception of time as mental timing of 120 sec is reduced by 28.3 sec in persons over 50 years compared to under 30 years.
Purpose / Aim of Study: To investigate if time spent on surgical hand antisepsis declines with age, and whether this can be explained by senior surgeons’ perception of time.
Materials and Methods: The study was performed as a cross sectional study at three orthopedic departments in Denmark. First, 32 orthopedists at different age were secretly timed during alcohol rub prior to surgery. Secondly, the individual perception of 120 seconds was examined on 64 orthopedists. Attitude towards surgical hand antisepsis was surveyed with a questionnaire send to all orthopedists at the departments.
Findings / Results: Orthopedists under 50 years of age used significantly longer time (mean 112 vs 74) on alcohol rub (p=0.034). No significant difference in perception of time (mean 135 vs 123) between orthopedists over and under 50 years (p = 0.102) was found. Nor was there any significant difference between age groups or rank when asked if they performed hand disinfection according to guidelines.
Conclusions: Orthopedists are not affected by mental aging as is the case in the normal population. Furthermore, orthopedics seem to be able to accelerate time when in the operating theater, a capability that is increasingly acquired with age. Orthopedists are aware of standard guidelines and convinced they follow them. This study presents new observations adding to the mythic nature of the orthopedic surgeon. Further studies are needed to understand the depth of the mystery.

135. Identification of procedures for simulation-based training in orthopedic surgery through a national general needs assessment
Amandus Gustafsson, Bjarke Viberg, Charlotte Paltved, Karen Lindorff-Larsen, Bjørn Ulrik Nielsen, Henrik Palm, Lars Konge, Leizl Joy Nayahangan
Copenhagen Academy for Medical Education and Simulation, University of Copenhagen and the Capital Region; Department of Orthopaedics and Traumatology, Kolding Hospital – part of Hospital Lillebaelt; Centre for Human Resources MidtSim, Region Midt; NordSim, Aalborg Universitetshospital; SimC, Odense Universitetshospital; Hip Fracture Unit, Department of Orthopedics, Copenhagen University Hospital Hvidovre; Copenhagen Academy for Medical Education and Simulation, University of Copenhagen and the Capital Region; Copenhagen Academy for Medical Education and Simulation, University of Copenhagen and the Capital Region


Background: Simulation-based training as an educational modality has grown increasingly popular over the last two decades. However, many interventions have relied more on what simulators were commercially available or local interests as opposed to the need of the trainees. This is in contrast to the theory that curriculum development is a stepwise approach starting with needs assessment.
Purpose / Aim of Study: The aim of this study was to conduct a national general needs assessment to identify technical procedures within orthopedic surgery that should be integrated into a simulation-based curriculum
Materials and Methods: A three-round iterative Delphi method was completed. Key persons (n=97) in the educational milieu were selected to participate. Round 1 was brainstorming where all possible procedures for simulation training were identified. In round 2, each department (n=27) answered a survey exploring frequency of procedures, how many should perform the procedure and risk for patients. Feasibility for simulation was explored by a steering group. In round 3, the key persons had the opportunity to eliminate and re-prioritize items from the prioritized list created during round 2.
Findings / Results: Round 1 had a response rate of 66%, round 2 100% and round 3 65%. In round 1, 194 items were included and after round 3, they were reduced to a prioritized list of 34 procedures. The five highest ranked procedures were 1) Basic principles of osteosynthesis, 2) Osteosynthesis of proximal femur fracture, 3) Surgical approaches of the lower extremity, 4) Basic surgical techniques and 5) Surgical approaches of the upper extremity.
Conclusions: This study generated a prioritized list of procedures that are highly relevant and suitable for simulation-based training and will serve as a foundation for future development of simulation-based curriculum in orthopedic surgery.

136. Mortality analysis and Failure to Rescue in dysvascular lower extremity amputees: implications for future treatment protocols.
Christian Wied, Nicolai Bang Foss, Peter Toft Tengberg, Gitte Holm, Anders Troelsen, Morten Tange Kristensen
Orthopaedic Surgery, Hvidovre Hospital; Anesthesiology and Intensive Care, Hvidovre Hospital; Orthopaedic Surgery, Hvidovre Hospital; Orthopaedic Surgery, Hvidovre Hospital; Orthopaedic Surgery, Hvidovre Hospital; Physical Medicine and Rehabilitation Research-Copenhagen (PMR-C), Hvidovre Hospital


Background: Extremely high 30-days mortality rates in excess of 30% have been reported following major dysvascular lower extremity amputations (LEA). The treatment of these patients is most often challenged by several competing co- morbidities. However, an enhanced treatment program seems to decrease 30- days mortality rates below 20%, but the potential and limitations for further reduction in mortality and morbidity are unknown.
Purpose / Aim of Study: To analyzes postoperative causes of 30-days mortality in an enhanced treatment program, and to introduce Failure to Rescue (FTR) in LEA surgery.
Materials and Methods: The medical charts of 195 consecutive LEA procedures were reviewed independently by three of the authors, and deaths during hospitalization following amputation were classified according to consensus.
Findings / Results: 31 (16%) patients died within 30-days after surgery. Patients with diabetes or transfemoral amputation (TFA) were in significantly higher risk of 30-days mortality in a log binominal regression model [p=0.007 & p=0.029)]. Patients who died had a higher incidence of sepsis [20% vs. 4%, p=0.008] and pneumonia [32% vs. 4%, p<0.001] compared to those alive. 4 deaths were classified as “definitely unavoidable”, 4 as “probably unavoidable”, and 23 as “FTR”. When compared to the survivors with complications, the FTR rate was 27%. Of the FTR deaths, 20 patients had at some time-point active lifesaving care curtailed. The 22 patients who died in the TFA sub- group received significantly more blood transfusions (p=0.020) compared to the 88 patients alive in the TFA group.
Conclusions: It seems warranted that future initiatives should be directed at enhanced sepsis and pneumonia prophylactic actions, in addition to close monitoring of hemodynamics in anemic patients, with the potential to further reduce morbidity and mortality rates.