Experimental
31. Double-dose cefuroxime concentrations in bone, knee joint, and subcutaneous adipose tissue – A randomized porcine microdialysis study
Andrea René Jørgensen , Pelle Hanberg , Mats Bue, Maja Thomassen, Nis Pedersen Jørgensen , Maiken Stilling
Orthopaedic Research Unit , Aarhus University Hospital ; Department of Orthopaedic Surgery , Horsens Regional Hospital ; Department of Orthopaedic Surgery , Aarhus University Hospital ; Orthopaedic Research Unit , Aarhus University Hospital ; Department of Infectious Diseases, Aarhus University Hospital ; 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.
Purpose / Aim of Study: To evaluate the time with concentrations
above relevant minimal inhibitory
concentrations (fT>MIC) of 4 μg/mL in bone,
knee joint, and subcutaneous adipose
tissue after double dose of cefuroxime given
as either one bolus administration (1x3,000
mg) or two single doses with a four-hour
interval (2x1,500 mg)
Materials and Methods: Sixteen female pigs (Danish Landrace
breed, weight 73-77 kg) were randomized
into two groups of eight: Group 1 received a
bolus administration of 3,000 mg
cefuroxime. Group 2 received two single
doses of 1,500 mg administered with a four-
hour interval. Microdialysis was applied for
sampling in cortical and cancellous bone,
knee joint, and subcutaneous adipose
tissue. Plasma samples were collected as
reference. Sampling was performed for
eight hours.
Findings / Results: During an 8 h sampling interval, the mean
percentage fT>MIC (4 μg/mL) across
compartments was longer for Group 2 (298
– 422 min) compared to Group 1 (221 – 269
min) (p<0.01). In cortical bone, there was a
tendency towards longer fT>MIC (4 μg/mL)
in Group 2 (298 min) compared to Group 1
(221 min) (p=0.053). Within 50 min after
administration, the mean concentration of 4
μg/mL was reached for both groups in all
compartments. In tissues 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).
Conclusions: A delayed tissue penetration was found in
all tissues, where a mean concentration of 4
μg/mL was reached within 50 min for both
groups in all compartments. During an 8 h
interval, double dose cefuroxime
administered as bolus 2x1,500 mg with a 4
h interval provides longer time above MIC
breakpoint for S. aureus (4 μg/mL) than a
single bolus of 3,000 mg cefuroxim.
However, to maintain sufficient tissue
concentrations during longer surgeries, re-
administration of cefuroxime (1,500 mg)
should be considered already 3 h after the
first administration.
32. What is so special about the myotendinous junction ?– a RNA-sequencing study
Jens Rithamer Jakobsen, Peter Schjerling, Michael Kjær, Abigail Mackey, Michael Rindom Krogsgaard
Department of sports traumatology M51, Copenhagen University Hospital, Bispebjerg and Frederiksberg; Institute of Sports Medicine, Department of Orthopaedic Surgery M, Copenhagen University Hospital, Bispebjerg and Frederiksberg; Institute of Sports Medicine, Department of Orthopaedic Surgery M, Copenhagen University Hospital, Bispebjerg and Frederiksberg; Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Science, University of Copenhagen; Department of sports traumatology M51, Copenhagen University Hospital, Bispebjerg and Frederiksberg
Background: The connection between the muscle fibers and
the tendon, name the myotendinous junction
(MTJ), is architecturally constructed to transmit
force between muscle and tendon, but at the
same time it is vulnerable to strain injury. In order
to explain why these injuries occur and suggest
how they can be prevented, a better
understanding of the composition and cellular
components of the MTJ is needed. Previous
studies have shown the presence of an unique
collagen type at the MTJ, Collagen XXII, which is
not demonstrated elsewhere in the skeletal
muscle system.
Purpose / Aim of Study: The purpose was to evaluate the gene expression of
the MTJ and compare it to the adjacent muscle and
tendon. We aimed to find new targets that are
unique to the MTJ and of importance for the strength
or recovery of the tissue. In addition, we wanted to
identify targets that are higher expressed at the MTJ
compared to the neighboring muscle and tendon.
Materials and Methods: Samples were collected from the superficial
digitorum flexor muscle from 20 horses, frozen
and sliced into sections containing muscle, MTJ
and tendon tissue before preparation for RT-
PCR. Based on the mRNA results a t-stochastic
neighboring embedded plot (t-SNE) was made
and sets of samples from 5 horses with the
clearest separation between tissues were
chosen for RNA sequencing. An expected
contribution of muscle and tendon was
calculated for all targets based on the known
expression of 2-300 of the most selective muscle
and tendon genes. Any variation between the
expected and measured gene expression was
regarded as expressed by the MTJ.
Findings / Results: No targets were found to be uniquely expressed at
the MTJ. Collagen XXIIα1 was expressed 17-fold
higher compared to the expected value. Generally,
genes involved in remodeling and reformation of
skeletal muscle fibers and extracellular matrix were
expressed to a larger extent at the MTJ.
Conclusions: Despite the MTJ being a region specialized in force
transmission with a highly specialized morphology
no genes could be demonstrated as being unique to
this region. The genes expressed higher in the MTJ
compared to muscle and tendon were related to
remodeling activities, and this confirms the previous
finding of high rates of remodeling at the MTJ.
33. ELECTRICAL IMPEDANCE CHARACTERIZATION OF BONE FRACTURE
Markus Frost, Ming Shen, Stanislav Zhekov, Ben Krøyer, Gert Frølund Pedersen, Søren Kold
Dept. of Orthopaedics and Interdisciplinary Orthopaedics, Aalborg University Hospital, Denmark; Dept. of Antennas, Propagation and Millimetre-wave Systems , Aalborg University, Denmark; Dept. of Antennas, Propagation and Millimetre-wave Systems , Aalborg University, Denmark; Dept. of Antennas, Propagation and Millimetre-wave Systems , Aalborg University, Denmark; Dept. of Antennas, Propagation and Millimetre-wave Systems , Aalborg University, Denmark; Dept. of Orthopaedics and Interdisciplinary Orthopaedics, Aalborg University Hospital, Denmark
Background: Differences in electrical characteristics of different
tissues can provide information of the tissue
composition at the fracture region. Real-time
monitoring of bone healing with electrical
impedance spectroscopy might provide information
for an individualized treatment of fracture patients.
However, electrodes must be placed at a distance to
the fracture site in order not to interfere with bone
healing.
Purpose / Aim of Study: We investigated whether electrical impedance
measurements from electrodes placed at a distance
to a bone defect can detect differences between
intact bone and bone defects in vivo.
Materials and Methods: Approval was granted from the Inspectorate of
the Animal Experimentation of Danish Ministry of
Justice. 6 rabbits were anaesthetized, and a
fracture protocol was subjected to both tibias.
Electrical impedance was measured in
frequencies from 10 Hz to 1 MHz at each step: 1)
intact bone, 2) medial defect, 3) medial and
lateral defect, 4) complete 2 mm bone defect.
One electrode was placed in the medullary canal
and two electrodes extracortical (lateral and
posterior) 2 mm from the defect. For each rabbit,
one tibia had measurements with a free inner
electrode and the other tibia had measurements
both with a nail and an isolated nail.
Findings / Results: For all tibias, the intact bone resulted in higher
impedance compared with the complete defect, and
this difference was most pronounced in the
frequency range of 1kHz to 100 kHz. This applied
for all types of electrodes including electrode, nail,
isolated nail. The isolated nail showed the biggest
impedance difference between the intact bone and
the complete defect. Incomplete bone defects had
lower impedance compared with intact bone, but no
consistent pattern for differences in impedance was
observed between the different applied defects.
Conclusions: Consistent impedance differences between intact
bone and complete defects were detected in-vivo in
rabbits. Further research is needed to explore
whether the presented method can be used to
characterize bone healing over time.
34. The ability of comorbidity indices to predict mortality in an orthopedic setting: A systematic review and meta-analysis
Mari Jørstad, Per Gundtoft, Julie Erichsen, Hagen Schmal, Bjarke Viberg
Orthopaedic Surgery and Traumatology, Lillebaelt Hospital, University Hospital of Southern Denmark; Orthopaedic Surgery and Traumatology, Lillebaelt Hospital, University Hospital of Southern Denmark; Orthopaedic Surgery and Traumatology, Lillebaelt Hospital, University Hospital of Southern Denmark; Clinic of Orthopaedic Surgery Medical Center, Faculty of Medicine, University of Freiburg, Germany; Orthopaedic Surgery and Traumatology, Lillebaelt Hospital, University Hospital of Southern Denmark
Background: Several comorbidity indices have been created to
measure and adjust for the estimated burden of
comorbidity.
Purpose / Aim of Study: The objective of this systematic review was to
evaluate and compare the ability of different
comorbidity indices to predict mortality in an
orthopedic setting.
Materials and Methods: A search string was developed in collaboration
with a scientific librarian. The search string was
used to extract possible studies from Embase,
Medline, and the Cochrane Library. Two
reviewers independently screened the studies
using Covidence. This study was registered in
Prospero and ROBINS-I assessment tool was
used to assess the risk of bias. The area under
the curve (AUC) was chosen as the primary
effect estimate. An exploratory meta-analysis
was made comparing the ability of the Elixhauser
Comorbidity Index (ECI) and the Charlson
Comorbidity Index (CCI) to predict in-hospital
and 1-year mortality.
Findings / Results: Of the 5338 studies identified, 16 met the
eligibility criteria. Most studies included patients
with either hip fractures (7 studies) or
arthroplasties (5 studies). The risk of bias was
serious for 2 studies and moderate for the
remaining.
Overall the predictive ability of the different
comorbidity indices ranged from poor (i.e. AUC
<0.70) to excellent (AUC >0.89).
The majority of the included studies only
compared the ECI and CCI. In-hospital mortality
for ECI and CCI was reported in 8 studies
yielding an overall effect size of 0.84 (CI 0.81-
0.88) for ECI and 0.83 (CI 0.79-0.86) for CCI.
The AUC values were generally lower for all
other time points ranging from 0.67 to 0.78. For
1-year mortality the overall effect size was 0.69
(CI 0.66-0.72) for ECI and 0.70 (CI 0.67-0.74) for
CCI.
Conclusions: ECI and CCI can equally be used to adjust for
comorbidities when analyzing in-hospital mortality in
an orthopedic setting. However, in general, both
indices have poor to fair AUC values for 30-day and
1-year mortality, where other indices might perform
better.
35. Sampling of the myotendinous junction – how can we do it?
Jens Rithamer Jakobsen, Peter Schjerling, Michael Kjær, Abigail Mackey, Michael Rindom Krogsgaard
Department of sports traumatology M51, Copenhagen University Hospital, Bispebjerg and Frederiksberg; Institute of Sports Medicine, Department of Orthopaedic Surgery M, , Copenhagen University Hospital, Bispebjerg and Frederiksberg; Institute of Sports Medicine, Department of Orthopaedic Surgery M, , Copenhagen University Hospital, Bispebjerg and Frederiksberg; Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen; Department of sports traumatology M51, Copenhagen University Hospital, Bispebjerg and Frederiksberg
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.
Purpose / Aim of Study: 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.
Findings / 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.
Conclusions: 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.
36. Manipulating the journal impact factor? The use of Journal-Self-Citations among orthopedic journals to boost journal rankings
Dorte Drongstrup, Søren Overgaard, David Minguillo
Research and Analysis Department, University Library of Southern Denmark; Orthopaedic research unit, Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Department of Clinical Research, University of Southern Denmark; , KTH Royal Institute of Technology
Background: The Journal Impact Factor (JIF) is often used
as an indicator of research quality by tenure,
promotion, and funding assessment
committees. Thus, a higher JIF could lead to
increased visibility for journals and more
publication submissions. This provides
incentives for journal editors to optimize in
accordance with the JIF formula; the number
of citations received in a given year to a
journal’s publications from previous two
years divided by the number of only articles
and reviews from previous two years.
However, the use of JIF to assess research
quality is highly problematic, since it can
easily be manipulated. A strategy to boost
the JIF-score is by increasing the rate of
Journal-Self-Citations (JSC) to the two
previous years (JIF-years), which increases
the number of citations (size of the
numerator).
Purpose / Aim of Study: The aim is to investigate to what extent
Orthopedic journals might use different
strategies to influence and increase their JIF-
scores.
Materials and Methods: All journals indexed in the subject category
Orthopedics by the Journal Citation Report
between 1997 and 2018 were analyzed. The
data source was the in-house database
version of Web of Science owned by the
Royal Institute of Technology (KTH). The
study covers 95 journals, 210,528
publications, and 3,990,809 citations. We
analyze the publishing and citation patterns
of these journals and apply different
measures to identify which strategies might
be the most frequent in the field to optimize
the impact factors and which journals might
take most advantage of these strategies to
boost their JIF and ranking.
Findings / Results: Our first results show that the rate of JSC to JIF-
years tend to be as almost double as high than
usual. Still, there are large variance in the JSC
intensity among journals. If the JSC to the JIF-
years are excluded, the impact factor on
average decreases 15%. For the 2018 JIF
ranking, four journals in the top10 changes
position when JCS are excluded.
Conclusions: The study finds a strong tendency for JSC in the
JIF-years. It suggests that the inclusion of JSC
in the calculation influences the JIF-scores and
ranking of journals.
37. Bacteriophage treatment against Staphyloccus aureus periprosthetic osteomyelitis in rats
Britt Siesing-Mejer, Mogens Kilstrup, Steen Sejer Poulsen, Kristine Stub Rønø, Ulla Rydahl Johansen, Niels Henrik Søe
Department of Orthopaedic Surgery Handsection, Hillerød University Hospital; DTU Bioengineering, Technical University Lyngby; Endocrinology and metabolism, The Panum Institute, KU; DTU Bioengineering, Technical University Lyngby; Department of Microbiology, , Rigshospitalet, KU; Handsection, Department of Orthopaedic, , Herlev and Gentofte university Hospital, Denmark
Background: Bacteriophages (phages) are virus-like entities
that only target bacteria and are composed of
protein-encapsulated phage chromosomes.
Using recognition proteins attached to the protein
capsule, phages bind to the surface of specific
bacteria and inject their chromosome into the
cytoplasm. Inside the cell the bacterial gene
expression machinery is hijacked by the phage
chromosome, to produce a large litter of
phage progeny, eventually killing the bacterium
and releasing the phages into the environment.
Purpose / Aim of Study: To investigate the ability of Bacteriophages to
eradicate S. aureus, in a knee prosthesis model of
osteomyelitis in rats.
Materials and Methods: Ten Sprague-Dawley rats had prosthesis
inserted in their left knee, and were divided into
three groups.
103 S. aureus MN8, ica+ was inserted into the
femoral and tibial bone marrow of the knee,
before insertion of the prosthesis. The study
included two bacteriophage groups with 4 rats in
each group and one control group with two rats:
One Bacteriophage group was given high dose
(106), and one low dose (103) of
bacteriophages,
before insertion of the prosthesis. Control rats
were given sterile saline (0.1 ml) and S. aureus
bacteria.
After two weeks the rats were sacrificed, and all
specimens were analyzed clinically,
radiographically, microbiologically and
histologically.
Findings / Results: In the group with high dose of bacteriophage, two
rats died of allergic reaction or cytokine storm.
The remaining two rats showed no reaction to
treatment. In the group with low dose of
bacteriophage, one rat died. One rat had a nearly
total
clearing of infection. The other two rats, showed a
significate reduction of infection in nearly all
parameters. One rat in the control group died of
unknown causes.
Conclusions: Bacteriophage treatment against S. aureus
osteomyelitis, reduced the infection in the low
dose group,
but no effect was seen in the group given high
dose of bacteriophage in any parameters. Two
rats died in the group given high dose of
bacteriophages because of cytokine storm.
Lower dose than 103 bacteriophages might
reduce the infection around the prosthesis, as
judged by all parameters.