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Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 49 - 49
1 Dec 2022
Charest-Morin R Bailey C McIntosh G Rampersaud RY Jacobs B Cadotte D Fisher C Hall H Manson N Paquet J Christie S Thomas K Phan P Johnson MG Weber M Attabib N Nataraj A Dea N
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In multilevel posterior cervical instrumented fusions, extending the fusion across the cervico-thoracic junction at T1 or T2 (CTJ) has been associated with decreased rate of re-operation and pseudarthrosis but with longer surgical time and increased blood loss. The impact on patient reported outcomes (PROs) remains unclear. The primary objective was to determine whether extending the fusion through the CTJ influenced PROs at 3 and 12 months after surgery. Secondary objectives were to compare the number of patients reaching the minimally clinically important difference (MCID) for the PROs and mJOA, operative time duration, intra-operative blood loss (IOBL), length of stay (LOS), discharge disposition, adverse events (AEs), re-operation within 12 months of the surgery, and patient satisfaction.

This is a retrospective analysis of prospectively collected data from a multicenter observational cohort study of patients with degenerative cervical myelopathy. Patients who underwent a posterior instrumented fusion of 4 levels of greater (between C2-T2) between January 2015 and October 2020 with 12 months follow-up were included. PROS (NDI, EQ5D, SF-12 PCS and MCS, NRS arm and neck pain) and mJOA were compared using ANCOVA, adjusted for baseline differences. Patient demographics, comorbidities and surgical details were abstracted. Percentafe of patient reaching MCID for these outcomes was compared using chi-square test. Operative duration, IOBL, AEs, re-operation, discharge disposittion, LOS and satisfaction were compared using chi-square test for categorical variables and independent samples t-tests for continuous variables.

A total of 206 patients were included in this study (105 patients not crossing the CTJ and 101 crossing the CTJ). Patients who underwent a construct extending through the CTJ were more likely to be female and had worse baseline EQ5D and NDI scores (p> 0.05). When adjusted for baseline difference, there was no statistically significant difference between the two groups for the PROs and mJOA at 3 and 12 months. Surgical duration was longer (p 0.05). Satisfaction with the surgery was high in both groups but significantly different at 12 months (80% versus 72%, p= 0.042 for the group not crossing the CTJ and the group crossing the CTJ, respectively). The percentage of patients reaching MCID for the NDI score was 55% in the non-crossing group versus 69% in the group extending through the CTJ (p= 0.06).

Up to 12 months after the surgery, there was no statistically significant differences in PROs between posterior construct extended to or not extended to the upper thoracic spine. The adverse event profile did not differ significantly, but longer surgical time and blood loss were associated with construct extending across the CTJ.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 39 - 39
1 Mar 2021
Aziz M Rosenzweig D Weber M
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Great strides have been made in the early detection and treatment of cancer which is resulting in improved survivability and more Canadians living with cancer. Approximately 80% of primary breast, lung, and prostate cancers metastasize to the spine. Poly-methyl methacrylate (PMMA) bone cement is one of the most commonly used bone substitutes in spine surgery. In clinical practice it can be loaded with various drugs, such as antibiotics or chemotheraputic drugs, as a means of local drug delivery. However, studies have shown that drugs loaded into PMMA cement tend to release in small bursts in the first 48–72 hours, and the remaining drug is trapped without any significant release over time. The objective of this study is to develop a nanoparticle-functionalized PMMA cement for use as a sustained doxorubicin delivery device. We hypothesize that PMMA cement containing mesoporous silica nanoparticles will release more doxorubicin than regular PMMA.

High viscosity SmartSet ™ PMMA cement by DePuy Synthes was used in this study. The experimental group consisted of 3 replicates each containing 0.24 g of mesoporous silica nanoparticles, 1.76 g of cement powder, 1ml of liquid cement monomer and 1 mg of doxorubicin. The control group consisted 3 replicates each containing 2.0 g of cement powder, 1ml of liquid cement monomer and 1 mg of doxorubicin. The experimental group contained an average of 8.18 ± 0.008 % (W/W) mesoporous silica nanoparticles. Each replicate was casted into a cylindrical block and incubated in a PBS solution which was changed at predetermined intervals for 45 days. The concentration of eluted doxorubicin in each solution was measured using a florescent plate reader. The mechanical properties of cement were assessed by unconfined compression testing. The effect of the doxorubicin released from cement on prostate and breast tumor cell metabolic activity was assessed using the Alamar Blue test.

After 45 days the experimental group released 3.24 ± 0.25 % of the initially loaded doxorubicin which was more than the 2.12 ± 0.005% released by the control group (p 0.03). There was no statistically significant difference in Young's elasticity modulus between groups (p 0.53). Nanoparticle functionalized PMMA suppressed the metabolic activity of prostate cancer by more than 50 percent but did not reach statistical significance. Nanoparticle functionalized PMMA suppressed the metabolic activity of breast cancer cells by 69 % (p < 0.05).

Nanoparticle-functionalized PMMA cement can release up to 1.53 times more doxorubicin than the standard PMMA. The use of mesoporous silica nanoparticles to improve drug release from PMMA cement shows promise. In the future, in vivo experiments are required to test the efficacy of released doxorubicin on tumor cell growth.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_7 | Pages 101 - 101
1 Jul 2020
Akoury E Ahangar P Luna ASR Nour A Weber M Rosenzweig D
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The spine is one of the most common sites of bony metastasis, with 80% of prostate, lung, and breast cancers metastasizing to the vertebrae resulting in significant morbidity. Current treatment modalities are systemic chemotherapy, such as Doxorubicin (Dox), administered after resection to prevent cancer recurrence, and systemic antiresorptive medication, such as Zolendronate (Zol), to prevent tumor-induced bone destruction. The large systemic doses required to elicit an adequate effect in the spine often leads to significant side-effects by both drugs, limiting their prolonged use and effectiveness. Recently published work by our lab has shown that biocompatible 3D-printed porous polymer scaffolds are an effective way of delivering Dox locally over a sustained period while inhibiting tumor growth in vitro. Our lab has also generated promising results regarding antitumor properties of Zol in vitro. We aim to develop 3D-printed scaffolds to deliver a combination of Zol and Dox that can potentially allow for a synergistic antitumor activity while preventing concurrent bone loss locally at the site of a tumor, avoiding long systemic exposure to these drugs and decreasing side effects in the clinical setting.

The PORO Lay polymer filaments are 3D-printed into 5mm diameter disks, washed with deionized water and loaded with Dox or Zol in aqueous buffer over 7 days. Dox or Zol-containing supernatant was collected daily and the drug release was analyzed over time in a fluorescence plate reader. The polymer-drug (Dox or Zol) release was tested in vitro on prostate and lung cancer cell lines and on prostate- or lung-induced bone metastases cells. Alternatively, direct drug treatment was also carried out on the same cells in vitro. Following treatment, all cells were subject to proliferation assay (MTT and alamar blue), viability assay (LIVE/DEAD), migration assay (Boyden chamber) and invasion assay (3D gel matrix). 3D-printed scaffolds loaded with both Dox and Zol will also be tested on cells.

We have established an effective dose (EC50) for prostate and lung cancer cell lines and bone metastases cells with direct treatment with Zol or Dox. We have titrated the drug loading of scaffolds to allow for a release amount of Dox at the EC50 dose over 7 days. In ongoing experiments, we are testing the release of Zol. We have shown Dox releasing scaffolds inhibit cancer cell growth in a 2D culture over 7 days using the above cellular assays and testing the scaffolds with Zol is currently being analyzed.

3D-printed porous polymers like the PORO Lay series of products offer a novel and versatile opportunity for delivery of drugs in future clinical settings. They can decrease systemic exposure of drugs while at the same time concentrating the drugs effect at the site of tumors and consequently inhibit tumor proliferation. Their ability to be loaded with multiple drugs can allow for achieving multiple goals while taking advantage of synergistic effects of different drugs. The ability to 3D-print these polymers can allow for production of custom implants that offer better structural support for bone growth.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_7 | Pages 81 - 81
1 Jul 2020
Aziz M Jarzem PF McIntosh G Weber M
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Seniors make up 16.9 percent of the Canadian population. Furthermore, the number of Canadians who are 65 years or older is increasing at an average rate of 20 percent every 5 years. In 2017, Sing etal reported that there is an increasing number of patients undergoing degenerative scoliosis surgery with the largest increase attributed to patients aged 65–69 years followed by those aged 70–74 years. Therefore, the purpose of this study is to assess the effectiveness of undergoing spinal surgery to correct degenerative spinal scoliosis in the ever-growing number of elderly patients. We hypothesize that age is not an independent prognostic factor of patients' outcomes followings degenerative scoliosis surgery.

A retrospective review of prospectively collected data within the Canadian Spine Outcome and Research Network (CSORN) was conducted. Data was analyzed using IBM-SPSS. ANOVA was used to analyze continuous variables while Chi Square test was used to analyze categorical variables. Significance level was p < 0.05.

There were 165 patients identified from the registry who met the inclusion criteria, 94 patients (57 %) were female. There were 102 (61.8 %) patients who were 65 years or older. The overall average age was 66.6 years (range 35–84, SD 8.6). There were 27 intra-operative complications, 44 peri-operative complications and 18 post operative complications. There was no statistically significant difference between the two age groups with regards to risk of developing intra-operative, perioperative and post operative complications. Patients who underwent degenerative scoliosis surgery reported an average improvement of 2.95±3.32, 3.64±3.50, 16.84±20.44 points on the back-pain scale, leg pain scale and the Oswestry Disability Index (ODI) respectively, there was no statistically significant differences in these measures between the two age groups.

As the number of patients undergoing degenerative scoliosis surgery increases, clinicians will need to determine which factors will significantly impact patients' outcomes following surgery. This study shows that age is not an independent prognostic factor when it comes to patients' outcomes following degenerative scoliosis surgery. In the future, research should examine the impact of age in conjunction with factors such as frailty, comorbidities and functional status on patient outcomes.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_7 | Pages 80 - 80
1 Jul 2020
Aziz M McIntosh G Johnson MG Fisher CG Weber M Goytan M
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Post-operative infection is a serious complication of spine surgery and can contribute to the strain on the healthcare system's resources. The purpose of this study is to determine what factors affect the risk of developing postoperative infection. We hypothesize that female gender, smoking, diabetes, having thoracolumbar procedures, having a neurological deficit, increased age, body mass index (BMI), American Society of Anaesthesiologists (ASA) score, blood loss, number of operative levels, operative time and undergoing non-elective surgery will increase the patients' risk of developing a post-operative infection.

A retrospective review of prospectively collected data within the Canadian Spine Outcome and Research Network (CSORN) was conducted. Data was analyzed using IBM-SPSS. Multivariable logistical regression analysis was conducted (odds ratios) to determine any association between the outcome and independent factors. Significance level was p < 0.05.

There were 7747 patients identified from the registry that had completed at least 12 weeks of follow up. There were 199 infections recorded representing a 2.6% risk of infection. There were no association found between the risk of developing a post operative infection and gender, smoking, diabetes, having thoracolumbar procedures, having a neurological deficit, ASA score, blood loss, number of operative levels and undergoing non-elective surgery. The following were associated with an increased risk of developing a post operative infection: Older age (adjusted OR=1.021, 95% CI=1.005–1.038, p < 0 .05), having an elevated BMI (adjusted OR=1.042, 95% CI=1.013–1.072, p < 0 .005), longer operative time (adjusted OR=1.002, 95% CI=1.001–1.004, p < 0 .001).

There is a 2.6% overall rate of post-operative spine infection across 20 Canadian centres. The factors that were associated with an increased risk of developing a post operative-infection were older age, increased BMI and longer operative time. This study establishes a benchmark against which the effectiveness of future interventions to reduce infection can be compared.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 70 - 70
1 Nov 2016
Aoude A Nooh A Fortin M Aldebayan S Abduljabbar F Jarzem P Ouellet J Weber M
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The objective of this paper is to demonstrate the difference in post-operative complication rates between Computer-assisted surgery (CAS) and conventional techniques in spine surgery. Several studies have shown that the accuracy of pedicle screw placement significantly improves with use of CAS. Yet, few studies have compared the incidence of post-operative complications between CAS and conventional techniques.

The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients that underwent posterior lumbar fusion from 2011 to 2013. Multivariate analysis was conducted to demonstrate the difference in post-operative complication rates between CAS and conventional techniques in spine surgery.

Out of 15,222 patients, 14,382 (95.1%) were operated with conventional techniques and 740 (4.90%) were operated with CAS. Multivariate analysis showed that patients in the CAS group had less odds to experience adverse events post-operatively (OR 0.57, P <0.001).

This paper examined the complications in lumbar spinal surgery with or without the use of CAS. These results suggest that CAS may provide a safer technique for implant placement in lumbar fusion surgeries.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 72 - 72
1 Nov 2016
Aoude A Aldebayan S Fortin M Nooh A Jarzem P Ouellet J Weber M
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Cervical spine fusion have gained interest in the literature since these procedures are now ever more frequently being performed in an outpatient setting with few complications and acceptable results. The purpose of this study was to assess the rate of blood transfusion after cervical fusion surgery, and its effect, if any on complication rates.

The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients that underwent cervical fusion surgery from 2010 to 2013. Univariate and multivariate regression analysis was used to determine post-operative complications associated with transfusion and cervical fusion.

We identified 11,588 patients who had cervical spine fusion between 2010 and 2013. The overall rate of transfusion was found to be 1.47%. All transfused patients were found to have increased risk of: venous thromboembolism (TBE) (OR 3.19, CI: 1.16–8.77), myocardial infarction (MI) (OR 9.12, CI: 2.53–32.8), increased length of stay (LOS) (OR 28.03, CI: 14.28–55.01) and mortality (OR 4.14, CI: 1.44–11.93). Single level fusion had increased risk of: TBE (OR 3.37, CI: 1.01–11.33), MI (OR 10.5, CI: 1.88–59.89), and LOS (OR 14.79, CI: 8.2–26.67). Multilevel fusion had increased risk of: TBE (OR 5.64, CI: 1.15–27.6), surgical site infection (OR 16.29, CI: 3.34–79.49), MI (OR 10.84, CI: 2.01–58.55), LOS (OR 26.56, CI: 11.8–59.78) and mortality (OR 10.24, CI: 2.45–42.71). ACDF surgery had an increased risk of: TBE (OR 4.87, CI: 1.04–22.82), surgical site infection (OR 9.73, CI: 2.14–44.1), MI (OR 9.88, CI: 1.87–52.2), LOS (OR 28.34, CI: 13.79–58.21) and mortality (OR 6.3, CI: 1.76–22.48). Posterior fusion surgery had increased risk of: MI (OR 10.45, CI: 1.42–77.12) and LOS (OR 4.42, CI: 2.68–7.29).

Our results demonstrate that although cervical fusions can be done as outpatient procedures special precautions and investigations should be done for patients who receive transfusion after cervical fusion surgery. These patients are demonstrated to have higher rate of MI, DVT, wound infection and mortality when compared to those who do not receive transfusion.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 75 - 75
1 Nov 2016
Aoude A Nooh A Fortin M Aldebayan S Jarzem P Ouellet J Weber M
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Hemorrhage and transfusion requirements in spine surgery are common. This is especially true for thoracic and lumbar fusion surgeries. The purpose of this papersi to determine predictive factors for transfusion and their effect on short-term post-operative outcomes for thoracic and lumbar fusions.

The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients that underwent lumbar or thoracic fusion surgery from 2010 to 2013. Univariate and multivariate regression analysis was used to determine predictive factors and post-operative complications associated with transfusion.

A total of 14,249 patients were included in this study; 13,586 had lumbar fusion and 663 had thoracic fusion surgery. The prevalence of transfusion was 35% for thoracic fusion and 17.5% for lumbar fusion. The multivariate analysis showed that age between 50–60 (OR 1.38, CI: 1.23–1.54), age between 61–70 (OR 1.65, CI: 1.40–1.95), dyspnea (OR 1.11, CI: 1.02–1.23), hypertension (OR 1.14, CI: 1.02–1.27), ASA class (OR 1.73, 1.18–1.45), pre-operative blood transfusion (OR 1.91, CI: 1.04–3.49), and extended surgical time (OR 4.51, CI: 4.09–4.98) were predictors of blood transfusion requirements for lumbar fusion. While only pre-operative BUN (OR 1.04, CI: 1.01–1.06) and extended surgical time (OR 4.70, CI: 3.12–6.96) were predictors of transfusion for thoracic fusion. In contrast, higher pre-operative hematocrit was protective against transfusion. Patients transfused who underwent lumbar fusion had an increased risk to develop superficial wound infection, deep wound infection, venous thromboembolism, myocardial infarction and had longer length of hospital stay. Patients transfused who underwent thoracic fusion were more likely to have venous thromboembolism and extended length of hospital stay. However, mortality was not associated with blood transfusion.

This study used a large database to characterise the incidence, predictors and post-operative complications associated with blood transfusion in thoracic and lumbar fusion surgeries. Pre- and post-operative planning for patients deemed to be at high-risk of requiring blood transfusion should be considered to reduce post-operative complication in this population.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 35 - 35
1 Nov 2016
Nooh A Zhang Y Sato D Dong Z Siegel P Barralet J Weber M
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Bone metastases are the most common cause of cancer-related pain and often lead to other complications such as pathological fractures and spinal cord compression. Bisphosphonates (BP) are a class of potent anti-resorptive agents commonly prescribed to retard osteoporosis progression. Interestingly, BP may have indirect anti-tumour properties through negative effects on macrophages, osteoclasts, endothelial cells and their ability to suppress matrix metalloproteinase (MMP) activity. Currently, the use of bisphosphonates for cancer therapy is generally restricted to high dose systemic delivery. The purpose of this study was to investigate the effects of direct local delivery of Zoledronate at the metastatic site in a mouse model of breast cancer metastasis to bone.

Seven days following intra-tibial inoculation with MDA-MB-231 (N = 1× 105) breast cancer cells in athymic mice, the experimental group (N = 11) was treated by direct infusion of 2µg of Zoledronate into the tibial lesion (three times/week for three weeks) and compared to vehicle-treated mice (N = 5). The formation of bone metastases and growth of the lesions were followed up by weekly bioluminescence imaging. In a subsequent experiment, a comparison of the effects of local versus systemic delivery of Zoledronate on the formation of osteolytic bone metastases was carried in athymic mice (N = 15). Seven days following intra-tibial inoculation with MDA-MB-231 breast cancer cells, the systemic group (N = 5) was treated with Zoledronate (0.025mg/kg) once per week for four weeks and compared to systemic delivery of vehicle (N = 4). Following treatment, the mice were sacrificed, and micro-CT images of the right tibia were obtained. Bone volume to tissue volume ratio (BV/TV%) was determined using µ-CT biomarkers.

The first experiment showed a statistically significant increase in mean bone volume/tissue volume ratio% (BV/TV%) in the treated group (7.0±1.54%) as compared to the control group (3.8±0.48%) (P <0.001, 95%CI=1.9–4.3). This corresponded to a net increase of 84.21% in response to Zoledronate treatment. Comparison between the local and systemic effects of Zoledronate also revealed a significant increase in the BV/TV% in the locally treated group (6.69±0.62%) when compared to the cohort administered systemic bisphosphonate treatment (4.03±0.44%) (P<0.001, 95%CI=1.24–3.20), corresponding to a net increase of 66.0%.

These preliminary results suggest that high dose sustained release of Zoledronate can lead to a significant inhibition of tumor-induced osteolysis. Moreover, comparison between local and systemic delivery revealed that the effect of local bisphosphonate administration exceeds the benefits of systemic delivery in terms of osteolysis inhibition. Lastly, the noted effects of Zoledronate local delivery triggers the need for further assessment of its anti-tumour activity.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_20 | Pages 96 - 96
1 Nov 2016
Aoude A Aldebeyan S Nooh A Weber M Tanzer M
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Computer assisted surgery (CAS) has gained popularity in orthopaedics for both total knee (TKA) and total hip arthroplasty (THA) in the past decades as a stereotactic device that provides the surgeon with real-time feedback on implant position based on electromagnetic or infrared based instruments. The purpose of this study was to assess the effect of CAS on 30-day complication rates following THA and TKA.

The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify all patients that underwent THA and TKA from 2011 to 2013, as well as any complication they had within 30-days of their surgery. Univariate and multivariate regression analysis was used to compare the post-operative complications in patients whose surgery involved the use of CAS with those by conventional surgical techniques.

We identified 104,550 patients who had THA (42,275 patients) and TKA (62,275 patients) procedures in the database between 2011 and 2013. Computer Assisted Surgery was used in 1,120 THA and 2,173 TKA procedures. There were higher overall adverse events (OR 1.40, CI: 1.22–1.59) in the Conventional group when compared to CAS for TKA. The rate of overall minor events (OR 1.38, CI: 1.21–1.58) and requirements for blood transfusion (OR 1.44, CI: 1.25–1.67) were higher in the Conventional group compared to the CAS group for TKA. However, rate of re-operation was significantly higher in the CAS group for TKA (OR 1.60, CI: 1.15–2.25). The results also showed higher overall adverse events (OR 2.61, CI: 2.09–3.26) in the Conventional group when compared to CAS for THA. The rate of overall minor events (OR 2.72, CI: 2.16–3.42) and requirements for blood transfusion (OR 3.27, CI: 2.52–4.25) was higher in the Conventional group whereas superficial wound infections (OR 0.46, CI: 0.46–0.81) were shown to be higher in the CAS group. The result also showed slightly longer operative times in CAS for both THA and TKA.

This study analysed a large patient database involving multiple institutions and surgeons and found that, overall, the use off CAS in primary total hip and total knee arthroplasty reduced the number of adverse events in the first 30-days postoperatively, compared to conventional surgical techniques. However, CAS was associated with an increased number of reoperations, superficial infections and operating time. The clinical benefits and disadvantages of CAS should be considered by arthroplasty surgeons when determining the potential benefit-cost ratio of this technology.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_8 | Pages 86 - 86
1 May 2016
Kasparek M Lazar M Weber M Ringl H Herold C Kasparek M Kubista B Windhager R Toepker M
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Introduction

Computer Tomography (CT) imaging has been limited to beam hardening artefacts until now. Literature has failed to describe sensitivity and specifity for loosening of endoprothesis in CTs, as metal artefacts have always influenced the diagnostic value of CTs.

In recent years a new technology has been developed, the Dual Energy CT. Dual Energy CT scanners simultaneously scan with two tubes at different energy levels, most commonly 100kVp and 140kVp. Furthermore pictures gained from Dual Energy CTs are post-processed with monoenergetic reconstruction, which increases picture quality while further reducing metal artefacts.

This promising technology has increased the diagnostic value preventing more radiation for the patients, for example in detection of kidney stones or to map lung perfusion. In the musculoskeletal imaging it has not been established yet and further clinical investigations are necessary.

Thus the aim of this study is to describe sensitivity and sensibility for endoprothesis loosening of this novel technology.

Material and Methods

53 prospective patients (31 total hip- and 22 total knee-arthoplasties) who were planned for revision surgery underwent preoperative Dual Energy CT examination. All scans were performed with a second-generation, dual-energy multi-detector CT scanner. And all pictures were post-processed with monoenergetic reconstruction.

Radiologists were blinded for patient´s history. Senior consultants, who are specialized in arthroplasty of the hip and the knee, performed surgery. Intraoperative information was used as gold standard.