A “two-stage exchange” remains the gold standard for treatment of the infected TKA in North America. Although there is interest in “one-stage exchange” this technique is not as familiar to many US surgeons and it is unclear if the reported results of Europe can be translated to North American practice. Specific concerns include the “radicalness” of the debridement required (which oftentimes includes the collateral ligaments, hence the popularity of hinged implants where this approach is common) and the use of fully cemented stems, which are extremely difficulty to remove if infection recurs. Thus while the idea of a one stage exchange is attractive to many North American surgeons, careful study will be required to determine if success can be achieved with a more “conservative” debridement and the use of cementless stems which are preferred by some surgeons. The basic principles of a two-stage exchange include: Thorough debridement of all infected appearing foreign material and all cement; Placement of an interval antibiotic loaded spacer (note that the addition of antibiotics to bone cement is NOT FDA approved) – 4–6g of antibiotics per pkg of cement; typically vancomycin + tobramycin; Higher viscosity cement may be associated with higher elution; The combination of antibiotics also leads to higher elution. Antibiotic spacers can be “articulating” or “static”. Potential advantages of an articulating spacer include greater patient comfort and an easier approach at the second stage exchange as soft tissue tension and range of motion is maintained. However, these spacers are oftentimes more costly and can break or dislocate. The first stage is followed by approximately 6 weeks of organism specific IV antibiotics. An interdisciplinary approach with an infectious disease specialist, internal medicine and a nutritionist optimises outcomes. Our protocol then includes weekly ESR and CRP to monitor their trend. These labs are re-checked two weeks after cessation of antibiotics to ensure the trend has not changed. The knee is routinely aspirated at this time point and the fluid obtained sent for a synovial fluid WBC count with differential and cultures (although the value of such cultures is controversial). We have found that while the ESR and CRP are significantly lower than prior to removal of the infected implant, they often times DO NOT normalise and there is no specific cut-off value that predicts persistent infection.
Infection after total knee arthroplasty poses formidable challenges to the surgeon. Once an infection is diagnosed, the identification of the organism and its sensitivity to antibiotics is essential. The host's healing capacity is vital. Optimisation of modifiable comorbidities, supplemental nutrition and cessation of smoking can improve wound healing. Surgical goals include debridement of necrotic tissue and elimination of the dead space. Intravenous antibiotics and a two-stage protocol are the standard of care. At our institution, the first stage is performed with an implant and antibiotic-cement composite. This articulating spacer maintains limb length and tissue compliance. The patient can maintain a functional status between stages. Definitive reconstruction is more readily accomplished with this method in contrast to the static spacer approach. The clinical efficacy of this protocol has been well documented in the literature.
Deep periprosthetic infection after hip or knee arthroplasty is a disconcerting problem for patient and surgeon alike. The diagnosis of infection is sometimes obvious but frequently requires that the surgeon maintain a substantial index of suspicion for infection as the cause of pain or poor outcome after any joint arthroplasty. While surgical debridement with component retention is appropriate in a subgroup of patients with an acute periprosthetic infection most delayed and chronic infections are best treated with component resection. The pre-eminent role of two-stage exchange as the definitive treatment was established over 30 years ago. Two-stage exchange remains the gold-standard in treatment with an established track record from multiple centers and with multiple different types of infecting organisms. Some of the historical problems with two-stage exchange, such as limited mobility during the interval stage, have been mitigated with the development of effective articulating spacer techniques. Further, the emergence of drug resistant bacteria and the possibility of fungal infection make two-stage exchange the best choice for the majority of patients with deep periprosthetic joint infection in 2015.
Infection after TKA remains a common reason for reoperation, and represents a significant burden for the patient and health care system. Having effective treatment strategies, therefore, is important to ensure the highest possible rate of success, and the lowest possible rate of reoperation due to treatment failure. This lecture will focus on the chronically infected TKA, where treatment options include either one stage exchange or two stage exchange. Proponents of one stage exchange cite lower costs, less morbidity, and reasonable success rates when compared to two stage exchange protocols. One must realise that strict selection criteria are generally used by proponents of single stage exchange. Favorable pathogens, healthy hosts, good soft tissues, minimal bone loss, etc. are generally used as indications to consider one stage exchange. Such “ideal” clinical situations, however, are exceedingly rare. The overwhelming majority of infected TKA in my practice involve resistant bacteria, significant bone loss, hosts with medical comorbidity, and often, poor soft tissues. In these situations, two stage exchange remains the gold standard to which all other interventions should be compared. With few exceptions, the published success rates for two stage procedures have been better, albeit slightly, than those published for one stage exchanges. Both static and articulating cement spacers have been used with good results. Further research is needed to better define the most effective treatment protocols, however, until further information is available, two stage exchange, with success rates of 80–90%, remains the most successful intervention for chronically infected TKA.
A “two-stage exchange” remains the gold standard for treatment of the infected THA in North America. Although there is interest in “one-stage exchange” this technique is predicated on the use of fixation of the revision implants with antibiotic loaded cement, which is not as popular in North America. Diagnosis is critical and in general consists of a screening serum ESR and CRP followed by selective aspiration if the above are abnormal and/or if the clinical history is suspicious. The aspirated fluid is sent for a synovial fluid WBC (cut-off approximately 3,000 WBC/μL), differential (cut-off 80% PMN) and culture. The basic tenets of treatment include:
Thorough debridement of all infected appearing cement and all foreign material Placement of an interval antibiotic loaded spacer (note that the addition of antibiotics to bone cement is NOT FDA approved) 4–6 g of antibiotics per pkg of cement; typically vancomycin + tobramycin Higher viscosity cement may be associated with higher elution Higher elution with combination of antibiotics Antibiotic spacers can be “articulating” or “static”. Potential advantages of an articulating spacer include greater patient comfort and an easier approach at the second stage exchange as leg length and soft tissue tension is maintained. However, these spacers are oftentimes more costly and can dislocate. May not be appropriate in cases where there is severe bone loss that cannot support partial weight bearing or if the abductors are compromised (higher risk of dislocation). The first stage is followed by approximately 6 weeks of organism specific IV antibiotics. An interdisciplinary approach with an infectious disease specialist, internal medicine and a nutritionist optimises outcomes. Our protocol then includes weekly ESR and CRP to monitor their trend. These labs are re-checked two weeks after cessation of antibiotics to ensure the trend has not changed. We have found that while the ESR and CRP are significantly lower than prior to the 1st stage, they often times DO NOT normalise and there is no specific cut-off value that predicts persistent infection. An intra-operative aspiration for synovial fluid WBC count and differential is obtained intra-operatively (cut-off values of approximately 3,000 WBC/μl and 80% PMN) and are the best tests to identify persistent infection.
It is well described that patients with bone and joint infections (BJIs) commonly experience significant functional impairment and disability. Published literature is lacking on the impact of BJIs on mental health. Therefore, the aim of this study was to assess health-related quality of life (HRQoL) and the impact on mental health in patients with BJIs. The AO Trauma Infection Registry is a prospective multinational registry. In total, 229 adult patients with long-bone BJI were enrolled between 1 November 2012 and 31 August 2017 in 18 centres from ten countries. Clinical outcome data, demographic data, and details on infections and treatments were collected. Patient-reported outcomes using the 36-Item Short-Form Health Survey questionnaire (SF-36), Parker Mobility Score, and Katz Index of Independence in Activities of Daily Living were assessed at one, six, and 12 months. The SF-36 mental component subscales were analyzed and correlated with infection characteristics and clinical outcome.Aims
Methods
Introduction. Trabecular Titanium is a biomaterial characterized by a regular three-dimensional hexagonal cell structure imitating trabecular bone morphology. Components are built via Electron Beam Melting technology in aone- step additive manufacturing process. This biomaterial combines the proven mechanical properties of Titanium with the elastic modulus provided by its cellular solid structure (Regis 2015 MRS Bulletin). Several in vitro studies reported promising outcomes on its osteoinductive and osteoconductive properties: Trabecular Titanium showed to significantly affect osteoblast attachment and proliferation while inhibiting osteoclastogenesis (Gastaldi 2010 J Biomed Mater
Equilibrative nucleoside transporter 1 (ENT1) transfers nucleosides, such as adenosine, across plasma membranes. We reported previously that mice lacking ENT1 (ENT1-KO) exhibit progressive ectopic calcification of spinal tissues, including the annulus fibrosus (AF) of intervertebral discs (J Bone Miner
Total knee arthroplasty (TKA) has been shown to improve knee joint function during gait post-operatively. However, there is considerable patient to patient variability, with most gait mechanics metrics not reaching asymptomatic levels. To understand how to target functional improvements with TKA, it is important to identify an optimal set of functional metrics that remain deficient post-TKA. The purpose of this study was to identify which combination of knee joint kinematics and kinetics during gait best discriminate pre-operative gait from postoperative gait, as well as post-operative from asymptomatic. Seventy-three patients scheduled to receive a TKA for severe knee osteoarthritis underwent 3D gait analysis 1 week before and 1 year after surgery. Sixty asymptomatic individuals also underwent analysis. Eleven discrete gait parameters were extracted from the gait kinematic and kinetic waveforms, as previously defined (Astephen et al., J Orthop
Objectives. Salubrinal is a synthetic agent that elevates phosphorylation
of eukaryotic translation initiation factor 2 alpha (eIF2α) and
alleviates stress to the endoplasmic reticulum. Previously, we reported
that in chondrocytes, Salubrinal attenuates expression and activity
of matrix metalloproteinase 13 (MMP13) through downregulating nuclear
factor kappa B (NFκB) signalling. We herein examine whether Salubrinal
prevents the degradation of articular cartilage in a mouse model
of osteoarthritis (OA). Methods. OA was surgically induced in the left knee of female mice. Animal
groups included age-matched sham control, OA placebo, and OA treated
with Salubrinal or Guanabenz. Three weeks after the induction of
OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At
three and six weeks, the femora and tibiae were isolated and the sagittal
sections were stained with Safranin O. Results. Salubrinal suppressed the progression of OA by downregulating
p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation
level of eIF2α, it did not suppress the progression of OA. Conclusions. Administration of Salubrinal has chondroprotective effects in
arthritic joints. Salubrinal can be considered as a potential therapeutic
agent for alleviating symptoms of OA. Cite this article: Bone Joint
Tendinopathy is a debilitating musculoskeletal
condition which can cause significant pain and lead to complete rupture
of the tendon, which often requires surgical repair. Due in part
to the large spectrum of tendon pathologies, these disorders continue
to be a clinical challenge. Animal models are often used in this
field of research as they offer an attractive framework to examine
the cascade of processes that occur throughout both tendon pathology and
repair. This review discusses the structural, mechanical, and biological
changes that occur throughout tendon pathology in animal models,
as well as strategies for the improvement of tendon healing. Cite this article: Bone Joint
Construction of a functional skeleton is accomplished
through co-ordination of the developmental processes of chondrogenesis,
osteogenesis, and synovial joint formation. Infants whose movement in
utero is reduced or restricted and who subsequently suffer
from joint dysplasia (including joint contractures) and thin hypo-mineralised
bones, demonstrate that embryonic movement is crucial for appropriate
skeletogenesis. This has been confirmed in mouse, chick, and zebrafish
animal models, where reduced or eliminated movement consistently yields
similar malformations and which provide the possibility of experimentation
to uncover the precise disturbances and the mechanisms by which
movement impacts molecular regulation. Molecular genetic studies have
shown the important roles played by cell communication signalling
pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone
morphogenetic protein. These pathways regulate cell behaviours such
as proliferation and differentiation to control maturation of the
skeletal elements, and are affected when movement is altered. Cell
contacts to the extra-cellular matrix as well as the cytoskeleton
offer a means of mechanotransduction which could integrate mechanical
cues with genetic regulation. Indeed, expression of cytoskeletal
genes has been shown to be affected by immobilisation. In addition
to furthering our understanding of a fundamental aspect of cell control
and differentiation during development, research in this area is
applicable to the engineering of stable skeletal tissues from stem
cells, which relies on an understanding of developmental mechanisms
including genetic and physical criteria. A deeper understanding
of how movement affects skeletogenesis therefore has broader implications
for regenerative therapeutics for injury or disease, as well as
for optimisation of physical therapy regimes for individuals affected
by skeletal abnormalities. Cite this article: Bone Joint
Objectives. There remains conflicting evidence regarding cortical bone strength
following bisphosphonate therapy. As part of a study to assess the
effects of bisphosphonate treatment on the healing of rat tibial
fractures, the mechanical properties and radiological density of
the uninjured contralateral tibia was assessed. Methods. Skeletally mature aged rats were used. A total of 14 rats received
1µg/kg ibandronate (iban) daily and 17 rats received 1 ml 0.9% sodium
chloride (control) daily. Stress at failure and toughness of the
tibial diaphysis were calculated following four-point bending tests. Results. Uninjured cortical bone in the iban group had a significantly
greater mean (standard deviation (. sd. )), p <
0.001, stress
at failure of 219.2 MPa (. sd. 45.99) compared with the control
group (169.46 MPa (. sd. 43.32)) following only nine weeks
of therapy. Despite this, the cortical bone toughness and work to
failure was similar. There was no significant difference in radiological
density or physical dimensions of the cortical bone. Conclusions. Iban therapy increases the stress at failure of uninjured cortical
bone. This has relevance when normalising the strength of repair
in a limb when comparing it with the unfractured limb. However,
the 20% increase in stress at failure with iban therapy needs to
be interpreted with caution as there was no corresponding increase
in toughness or work to failure. Further research is required in
this area, especially with the increasing clinical burden of low-energy
diaphyseal femoral fractures following prolonged use of bisphosphonates. Cite this article: Bone Joint
High-quality randomised controlled trials (RCTs)
evaluating surgical therapies are fundamental to the delivery of
evidence-based orthopaedics. Orthopaedic clinical trials have unique
challenges; however, when these challenges are overcome, evidence
from trials can be definitive in its impact on surgical practice.
In this review, we highlight several issues that pose potential
challenges to orthopaedic investigators aiming to perform surgical randomised
controlled trials. We begin with a discussion on trial design issues,
including the ethics of sham surgery, the importance of sample size,
the need for patient-important outcomes, and overcoming expertise
bias. We then explore features surrounding the execution of surgical
randomised trials, including ethics review boards, the importance
of organisational frameworks, and obtaining adequate funding. Cite this article: Bone Joint
The aim of this study was to review the role
of clinical trial networks in orthopaedic surgery. A total of two
electronic databases (MEDLINE and EMBASE) were searched from inception
to September 2013 with no language restrictions. Articles related
to randomised controlled trials (RCTs), research networks and orthopaedic
research, were identified and reviewed. The usefulness of trainee-led
research collaborations is reported and our knowledge of current
clinical trial infrastructure further supplements the review. Searching
yielded 818 titles and abstracts, of which 12 were suitable for
this review. Results are summarised and presented narratively under
the following headings: 1) identifying clinically relevant research
questions; 2) education and training; 3) conduct of multicentre
RCTs and 4) dissemination and adoption of trial results. This review
confirms growing international awareness of the important role research
networks play in supporting trials in orthopaedic surgery. Multidisciplinary
collaboration and adequate investment in trial infrastructure are crucial
for successful delivery of RCTs. Cite this article: Bone Joint
Objectives. The purpose of this study was to evaluate in vivo biocompatibility
of novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic
acid) (PLAGA) composites for applications in bone and tissue regeneration. Methods. A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted
subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm
PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight
and 12 weeks post-implantation were compared with control (Sham)
and PLAGA (five rats per group/point in time). Rats were observed
for signs of morbidity, overt toxicity, weight gain and food consumption,
while haematology, urinalysis and histopathology were completed
when the animals were killed. Results. No mortality and clinical signs were observed. All groups showed
consistent weight gain, and the rate of gain for each group was
similar. All groups exhibited a similar pattern for food consumption.
No difference in urinalysis, haematology, and absolute and relative
organ weight was observed. A mild to moderate increase in the summary toxicity
(sumtox) score was observed for PLAGA and SWCNT/PLAGA implanted
animals, whereas the control animals did not show any response.
Both PLAGA and SWCNT/PLAGA showed a significantly higher sumtox
score compared with the control group at all time intervals. However,
there was no significant difference between PLAGA and SWCNT/PLAGA
groups. Conclusions. Our results demonstrate that SWCNT/PLAGA composites exhibited in
vivo biocompatibility similar to the Food and Drug Administration
approved biocompatible polymer, PLAGA, over a period of 12 weeks.
These results showed potential of SWCNT/PLAGA composites for bone
regeneration as the low percentage of SWCNT did not elicit a localised
or general overt toxicity. Following the 12-week exposure, the material
was considered to have an acceptable biocompatibility to warrant
further long-term and more invasive in vivo studies. Cite this article: Bone Joint
It is nowadays widely recognized that patient satisfaction following knee arthroplasty strongly depends on ligament balancing. To obtain this balancing, the occurring ligament strain is assumed to play a crucial role. To measure this strain, a method is described in this paper that allows full field 3D evaluation of the strains. The latter is preferred over traditional measurement techniques, e.g. displacement transducers or strain gauges, as human soft tissue is not expected to deform uniformly due to its highly inhomogeneous and anisotropic properties. To facilitate full field strain measurements, the 3D digital image correlation (DIC) technique was adopted. This technique was previously validated by our research group on human tissue. First, a high contrast speckle pattern was applied on the sMCL. Therefore, the specimens are first coated with a small layer of methylene blue. Following, a random white speckle pattern is applied. During knee flexion, two cameras simultaneously take pictures of the deforming region at predefined flexion angles. Using dedicated software, the captured images are eventually combined and result in 3D full field strains and displacements. Using this method, the strain distribution was studied in six cadaveric knees during flexion extension movement. Therefore, the femur was rigidly fixed in a custom test rig. The tibia was left unconstrained, allowing the six degrees of freedom in the knee. A load was applied to all major muscles in physiological directions of each muscle by attaching a series of calibrated weights (Farahmand et al., J Orthop
Introduction. Incorrect restoration of the joint line during total knee arthroplasty (TKA) can result in joint instability, anterior knee pain, limited range of motion, and joint stiffness. Although restoration of the correct joint line (i.e., creating an optimal gap in extension and flexion) should be considered in all TKA procedures, no surgical techniques have been established for restoring it. We performed the femoral posterior condylar precut technique (Kaneyama R. Bone Joint
Objective . A clinical investigation into a new bone void filler is giving
first data on systemic and local exposure to the anti-infective
substance after implantation. Method . A total of 20 patients with post-traumatic/post-operative bone
infections were enrolled in this open-label, prospective study.
After radical surgical debridement, the bone cavity was filled with
this material. The 21-day hospitalisation phase included determination
of gentamicin concentrations in plasma, urine and wound exudate, assessment
of wound healing, infection parameters, implant resorption, laboratory
parameters, and adverse event monitoring. The follow-up period was
six months. . Results . Systemic exposure to gentamicin after implantation was very low
as local gentamicin concentrations were measured in wound exudate
after six to ten hours. There were no signs of infectious complication
throughout the clinical phase. Four patients had recurrent infections
several weeks to months after implantation. The outcome was deemed successful
by remission of infection in 16 (80%) of these problematic long-term
treated patients. Safety laboratory measurements did not indicate
nephrotoxic or hepatotoxic effects. . Conclusions . Local application of calcium sulphate/carbonate bone void filler
comprising gentamicin revealed sufficient active local levels of
the antibiotic by simultaneous significant low systemic exposure
in patients with mostly chronic osteomyelitis/osteitis. The material
was safe and well tolerated. Cite this article: Bone Joint
Introduction. Total knee arthroplasty (TKA) designs evolve as evidence accumulates on natural and prosthetic knee function. TKA designs based upon a medially conforming tibiofemoral articulation seek to reproduce essential aspects of normal knee stability and have enjoyed good clinical success and high patient satisfaction for over two decades. Fluoroscopic kinematic studies on several medially conforming knee designs show extremely stable knee function, but very small ranges of tibial axial rotation compared to healthy knees. The GMK Sphere TKA is a recent evolution in medially-conforming TKA designs that adopts a sagittally unconstrained lateral tibiofemoral articulation to allow more natural tibial rotation. This study was conducted to quantify motions in knees with this prosthesis to address two questions:. Does the medially conforming GMK Sphere design provide an AP-stable articulation that provides for tibiofemoral translations that are comparable to, but not larger than, translations measured in natural knees?. Does the medially conforming GMK Sphere design provide sufficient rotatory laxity to allow tibiofemoral rotations comparable to, but not larger than, rotations measured in natural knees?. Materials and Methods. Fifteen patients (9 females), mean age 65 years and mean BMI of 30 ±3, consented to participate. Sixteen knees received the GMK Sphere TKA. Mean Oxford Knee Score (OKS) improved significantly from 19±7 to 40±3 six months post surgery (P< 0.0001). On the day of the study, the mean OKS, Knee Society Score, EQ5D and Heath status scores were 40, 87, 0.83 and 85 respectively. Mean ROM from active maximum extension till maximum supine flexion was 108°±8°. Motions in 16 knees were observed using pulsed-fluoroscopy during a range of activities. Subjects were observed in maximum flexion kneeling and lunging positions, and in stepping up/down on a 22cm step. Model-image registration methods were used to quantify three-dimensional knee motions from digitized fluoroscopic images. Results. Tibial internal rotation averaged 8° during lunge and kneeling activities. During lunging, the medial and lateral condyles were an average of 2mm and 8mm posterior to the tibial sulcus, respectively, and 2mm and 9mm posterior to the tibial sulcus during kneeling. During the stair-stepping activity, the medial condyle did not translate significantly, while the lateral condyle moved 5mm posteriorly with flexion, accompanying 5° tibial internal rotation. Discussion. The GMK Sphere TKA was designed to provide intrinsic stability through a medially conforming articulation, and provide for more natural tibial rotation with an unconstrained lateral articulation. Fluoroscopic observation of these knees during lunge, kneel and stair-stepping activities showed a stable medial articulation with little translation, and a lateral articulation translating in direct relation to tibial rotation. Tibial rotation during kneeling (8° average) was approximately twice that observed in knees with an earlier medially conforming TKA design (Moonot et al., Knee Surg Sports Traumatol Arthrosc, 2009) and similar to that observed in natural knees with medial osteoarthritis (Hamai et al., J Orthop