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.