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Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 246 - 246
1 Jul 2011
Kuzyk PRT Davies JE Schemitsch EH
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Purpose: The purpose of this study was to relate the extent of reaming to bone formation occurring around a critical sized defect in the tibia.

Method: Eleven canines were allocated into 2 groups: empty (N=5) or iliac crest autograft (N=6). All tibiae were reamed to 7.0 mm and fixed with a 6.5 mm statically locked intramedullary nail after creation of an 8.0 mm diaphyseal defect. The extent of reaming of the canal was dependent on the cross-sectional area of the tibia as all tibiae were reamed to 7.0 mm. Fluorescent markers were given at different times: calcein green (6 weeks), xylenol orange (9 weeks), and tetracycline (11 and 14 weeks). Animals were sacrificed at 15 weeks and perfused with a barium compound. Radiography, Micro CT, brightfield microscopy and fluorescent microscopy were used for analysis.

Results: Bone and vasculature volume within the defect were reported as a percentage of the total volume of the defect. Linear regression analysis of percent bone volume (dependent variable) and canal area (independent variable) provided a Pearson correlation coefficient of 0.925 (p=0.025) for the empty group and 0.244 (p=0.641) for the autograft group. Linear regression analysis of percent vasculature volume (dependent variable) and canal area (independent variable) provided a Pearson correlation coefficient of 0.784 (p=0.117) for the empty group and −0.146 (p=0.783) for the autograft group. Bone formation at osteotomy sites was defined as the distance from the original osteotomy site to the tip of newly formed bone. Linear regression analysis of bone formation at the osteotomy sites (dependent variable) and canal area (independent variable) provided a Pearson correlation coefficient of 0.132 (p=0.832) for the empty group and −0.937 (p=0.006) for the autograft group. Bone formation rates were reported as the distance between the fluorescent labels. Bone formation rate was less within the endosteum, cortex and periosteum with extensive reaming in empty samples.

Conclusion: Our results suggest that the acute management of tibia fractures with bone defects should involve limited reaming. This does not apply when the defect is autografted. Limited reaming may be defined by the cross-sectional area of the tibia in ratio to that of the reamer.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 245 - 245
1 Jul 2011
Atesok KI Li R Schemitsch EH
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Purpose: Endothelial Progenitor Cells (EPCs) have been proven to contribute to formation of new blood vessels. The objective of this study was to evaluate the effects of local EPC therapy on the stimulation of angiogenesis at a fracture site and the promotion of bone healing by increasing osteogenesis and callus formation.

Method: Rat bone marrow EPCs were isolated and cultured. A segmental bone defect (4mm.) was created in the rat femur diaphysis and stabilized with a mini-plate. A gelfoam piece impregnated with a solution of EPCs (1x106) was placed into the fracture gap. Control animals received only saline-gelfoam with no cells. In total, 42 rats were studied: 21 in EPC and 21 in control groups. Seven animals were sacrificed from each group at one, two, and three weeks post-operatively. Plain radiographs of the operated femur were taken before sacrifice. Operated femurs were harvested and the specimens from the osteotomy site were collected for histological evaluation. The x-rays were scored in a scale from zero to five according to the percentage and the intensity of the bone filling at the osteotomy site. Hematoxylin-eosin stained slides were evaluated for new vessel formation and the amount of bone tissue.

Results: Radiographically, at three weeks, the mean score for the EPC group was 4.5 with five out of seven animals having bridging callus; whereas for the control group, the mean score was 2.2 with no bridging callus formation. At two weeks, EPC treated animals had a mean score of 2.4, and the control group had a score of 1. Bone formation was insignificant at one week in either group, however, the scores tended to be higher in the EPC group animals than the control; 0.6 to 0.3 respectively. Histological evaluation revealed that the specimens from EPC treated animals had abundant spicules of trabecular bone containing predominantly bone cells, osteoid, and new vessels. Conversely, control animals had scarce trabecular bone with markedly less bone cells and vessels.

Conclusion: Local EPC therapy stimulates angiogenesis and increases osteogenesis and callus formation post fracture. Our report encourages further investigation of the local use of EPCs as a potential therapy to promote bone regeneration.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 259 - 259
1 Jul 2011
Goldstein C Schemitsch EH Bhandari M Mathew G Petrisor B
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Purpose: Identifying optimal treatment strategies in patients with traumatic foot and ankle injuries has been hampered by the variety of different measurement tools and lack of validation of generic and foot-specific functional measures. It remains plausible that the choice of functional outcome measure may influence our ability to accurately measure treatment effects. This prospective observational study aims to correlate the scores across six functional outcome measures in patients with traumatic foot and ankle injuries and to examine agreement of scores and patients’ subjective health status.

Method: Patients with traumatic foot or ankle injuries completed two generic, the SF-12 Health Survey and the Short Musculoskeletal Functional Assessment (SMFA), and four specific health outcome measures, the Foot Function Index (FFI), Foot and Ankle Ability Measure (FAAM), American Academy of Orthopedic Surgeons (AAOS) Foot and Ankle Questionnaire and the American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, at a single follow-up visit. Raw scores were calculated and used to assign patients to a categorical functional level (excellent, very good, good, fair or poor). Agreement between the assignments was assessed and Pearson correlation co-efficients were calculated for each pair of outcome scores. Statistical significance was determined using an α of 0.05.

Results: 52 patients (mean age 43.3 ± 16.8 years) were enrolled at a mean follow-up of 15.5 months. All correlations except for that between the AOFAS ankle-hindfoot scale and the mental component of the SF-12 were statistically significant. The strongest correlations were found between the SMFA, FFI, AAOS Foot and Ankle Questionnaire and the FAAM. Despite significant correlation between scores and patients’ subjective functional outcome, there was minimal agreement between assigned categorical functional levels.

Conclusion: The high correlations between scores on the generic and foot-specific functional measures suggest that it is likely unnecessary to use more than one instrument when examining functional outcome in patients with traumatic foot and ankle injuries. Generic tools also appear to function as well as specific scores in this population. However, assignment of patients to a categorical functional level based on raw outcome scores must be performed with caution as the results obtained may not accurately reflect functional outcome.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 254 - 254
1 Jul 2011
Lewis P Olsen M Schemitsch EH Waddell JP
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Purpose: While the durability of most uncemented femoral stems remains unknown, it is the aim of this study to demonstrate Echelon Primary femoral stem performance with regard patient outcome and overall implant survival.

Method: Between February 1998 and March 2007, 428 patients received the Echelon Primary stem. The mean age of each patient was 58.1 (SD 11.1, Range 20–87). Body mass index averaged 30.5 kg/m2 (SD 5.8, Range 17.7–58.2). The majority of patients received a Reflection uncemented acetabular component (91%) and an ultra high molecular weight polyethylene liner (76.5%), although the highly cross linked polyethylene is now used with increased frequency, used in 31% of hips since 2005. The majority of femoral heads were cobalt chrome (79.3%).

Results: Kaplan Meier survivorship for the Echelon Femoral stem with revision for aseptic loosening as end point at 100 months is 99.3% (95% CI 97.1–99.8). Taking revision for any reason as the end point the Kaplan Meier survivorship is 98.3% at 100 months (95% CI 95.9–99.3). A pre-operative WOMAC score was available for 345 of the 392 patients with mean score of 43.5 (95% CI 41.6–45.4). At the three-month post-operative review the mean WOMAC score was significantly increased to 74.54 (95% CI 72.7–76.3)(p< 0.001) and by 1 year 84.3 (95% CI 80.5–88.1). At subsequent years, the modified WOMAC score remained at a plateau of around 80. General health assessment using the SF-36 shows an improvement in the physical component score from 33.1 (95% CI 32.3–33.9) preoperatively to 42.6 (95% CI 41.7–43.6)(p< 0.001) at three months and 48.19 (95% CI 44.2–52.2) at latest follow up. The mental component scores increased from 48.7 (95% CI 47.6–49.9) to 51.4 (95% CI 50.3–52.4)(p< 0.001) and 53.5 (95% CI 50.3–56.6) respectively.

Conclusion: This large prospective review of the Echelon Primary femoral stems reveals an excellent survivorship of the stem with a 99.3% survival at 8 years with regard aseptic loosening and 98.3% survival including revision for any reason. Patient outcome scores are significantly improved and subsequently maintained. There have been no changes with regard to manufacture or design of the stem within the period of review.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 245 - 245
1 Jul 2011
Kuzyk PRT Schemitsch EH Davies JE
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Purpose: The aim of our study was to evaluate bone formation and angiogenesis produced within a biodegradable poly-D, L-lactide-co-glycolide acid/calcium phosphate (PLGA/CaP) scaffold when used to treat a diaphyseal tibia defect and compare this to an iliac crest autograft or an empty defect.

Method: An 8.0 mm diaphyseal defect was created in a canine tibia model. All tibiae were reamed to 7.0 mm and fixed with a 6.5 mm statically locked intramedullary nail. Eighteen canines were allotted into three treatment groups:

empty (N=5),

iliac crest autograft (N=6), or

PLGA/CaP biodegradable scaffold Tissue Regeneration Therapeutics Inc., ON, Canada) (N=7).

Fluorescent markers were given at different times: calcein green (six weeks), xylenol orange (nine weeks), and tetracycline (11 and 14 weeks). Animals were sacrificed at 15 weeks and perfused with a barium compound. Radiography, Micro CT, and brightfield and fluorescent microscopy were used for analysis.

Results: Micro CT and brightfield images of scaffold samples displayed multiple vessels (10 to 100μm) within the scaffold. The bone volume and vasculature volume (measured with Micro CT) within the tibial defect site were reported as a percentage of the total volume of the defect site. The percent bone volume within the defect site was not different between treatment groups (p=0.112). There was greater percent vasculature volume in the scaffold group than the autograft group (p< 0.001). Bone formation at the osteotomy sites was defined as the distance from the original osteotomy site to the tip of newly formed bone. Osteotomy bone formation was significantly greater in the scaffold group than the autograft group (p=0.015). Osteotomy sites associated with greater angiogenesis displayed greater bone formation. Bone formation rates were reported as the distance between the fluorescent bone labels. Autograft samples had the greatest bone formation rates within the periosteum. Autograft and scaffold samples had the greatest rate of bone formation within the cortex.

Conclusion: Our canine tibial defect model provides a satisfactory facsimile of the traumatic tibia fracture with associated bone loss. The PLGA/CaP biodegradable scaffold we have employed promotes angiogenesis within a defect and could be used in conjunction with autografting.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 255 - 255
1 Jul 2011
Olsen M Davis ET Waddell JP Schemitsch EH
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Purpose: Hip resurfacing is a technically demanding alternative to total hip arthroplasty. Placement of the initial femoral guidewire utilizing traditional mechanical jigs may lead to preparatory errors and a high degree of variability in final implant stem-shaft angle (SSA). Intraoperative computer navigation has the potential to decrease preparatory errors and provide a reliable method of femoral component placement. The current study evaluated the accuracy and learning curve of 140 consecutive navigated hip resurfacing arthroplasties.

Method: Between October 2005 and May 2007, 140 consecutive Birmingham Hip Resurfacings were performed on 132 patients (107 male, 25 female). The mean age of the cohort was 51.2 years (range 25–82). Indications for surgery included osteoarthritis (n=136) and avascular necrosis (n=4). Preoperative templating was performed using digital AP unilateral hip radiographs. Neck-shaft angles (NSA) were digitally measured and relative implant stem-shaft angles planned. The central guidewire was drilled and verified intra-operatively using an imageless navigation system. Implant stem-shaft angles were assessed using 3 month post-operative radiographs.

Results: Pre-operative templating determined a mean NSA of 132.2 degrees (SD 5.3 degrees, range 115–160). The planned SSA was a relative valgus alignment of 9.5 degrees (SD 2.6 degrees). The post-operative SSA differed from the planned SSA by 2.5 degrees (SD 1.9 degrees, range 0–8). The final SSA measured within ±5 degrees of the planned SSA in 89% of cases. Of the remaining 11% of cases, all measurements erred in valgus. No cases of neck notching or varus implant alignment occurred in the series. The mean navigation time for the entire series was 18 minutes (SD 6.6 minutes, range 10–50). A learning curve was observed with respect to navigation time, with a significant decrease in navigation time between the first 20 cases and the remainder of the series. There was no evidence of a learning curve for implant placement accuracy.

Conclusion: Imageless computer navigation shows promise in optimizing preparation of the femoral head and reducing the introduction of mechanical preparatory factors that predispose to femoral neck fracture. Navigation may afford the surgeon an accurate and reliable method of femoral component placement with negligible learning curve.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 5 | Pages 593 - 600
1 May 2011
Kuzyk PRT Saccone M Sprague S Simunovic N Bhandari M Schemitsch EH

We conducted a systematic review and meta-analysis of randomised controlled trials comparing cross-linked with conventional polyethylene liners for total hip replacement in order to determine whether these liners reduce rates of wear, radiological evidence of osteolysis and the need for revision. The MEDLINE, EMBASE and COCHRANE databases were searched from their inception to May 2010 for all trials involving the use of cross-linked polyethylene in total hip replacement. Eligibility for inclusion in the review included the random allocation of treatments, the use of cross-linked and conventional polyethylene, and radiological wear as an outcome measure. The pooled mean differences were calculated for bedding-in, linear wear rate, three-dimensional linear wear rate, volumetric wear rate and total linear wear. Pooled risk ratios were calculated for radiological osteolysis and revision hip replacement. A search of the literature identified 194 potential studies, of which 12 met the inclusion criteria. All reported a significant reduction in radiological wear for cross-linked polyethylene.

The pooled mean differences for linear rate of wear, three-dimensional linear rate of wear, volumetric wear rate and total linear wear were all significantly reduced for cross-linked polyethylene. The risk ratio for radiological osteolysis was 0.40 (95% confidence interval 0.27 to 0.58; I2 = 0%), favouring cross-linked polyethylene. The follow-up was not long enough to show a difference in the need for revision surgery.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 3 | Pages 298 - 306
1 Mar 2011
van der Weegen W Hoekstra HJ Sijbesma T Bos E Schemitsch EH Poolman RW

We systematically reviewed the peer-reviewed literature to relate the survival of hybrid metal-on-metal hip resurfacing arthroplasty devices to a National Institute of Clinical Excellence (NICE) benchmark for choosing a primary total hip replacement, which is a survival rate of 90% at a follow-up of ten years.

A total of 29 articles (10 621 resurfaced hips) met the inclusion criteria. The mean follow-up ranged from 0.6 to 10.5 years and the survival of the implant ranged from 84% to 100%. Of the 10 621 hips, 370 were revised (3.5%), with aseptic loosening as the most frequent mode of failure.

None of the hip resurfacing arthroplasty implants used to date met the full ten-year NICE benchmark of survival. A total of 13 studies showed satisfactory survival compared with the three-year NICE benchmark.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 25 - 25
1 Mar 2010
McKee MD Thompson C Wild L Schemitsch EH
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Purpose: In a prospective randomized clinical trial, we have previously reported the “limb-specific” results comparing operative (plate fixation) versus non-operative (sling) treatment for completely displaced fractures of the shaft of the clavicle. We also sought to determine the effect that a fracture of the shaft of the clavicle had on general health status, as measured by the SF-36 General Health Status instrument. We then evaluated the effects of different treatment methods (operative versus non-operative), on general health scores.

Method: We performed a multi-center, randomized clinical trial of operative versus non-operative treatment of completely displaced clavicular shaft fractures in 111 patients. In addition to radiographic, surgeon-based, and limb-specific data we prospectively gathered SF-36 questionnaires at baseline, and at 6 weeks and 3, 6, 12, and 24 months post-injury.

Results: Results: Both groups had SF-36 scores equivalent to or slightly superior to population norms at baseline. A clavicular shaft fracture had a significant negative effect on SF-36 scores (especially the physical components) in both groups at 6 weeks (p< 0.01) and 3 months (p< 0.01). There was a statistically greater decrease in Physical Component Scores (PCS) in the non-operative group compared to the operative group (P< 0.05). At 6 months, scores had returned to pre-operative levels in the operative group, but remained significantly decreased in the non-operative group (p=0.04). This difference persisted at the one and two year points.

Conclusion: A displaced fracture of the clavicular shaft has a clinically significant negative effect on general health status scores. This effect can be mitigated by primary operative fixation, which restores scores to normal levels by six months post-injury. Patients treated non-operatively for a displaced fracture of the shaft of the clavicle demonstrated lower PCS scores at two years post-injury. This information is useful in counseling patients with regards to treatment options following displaced fractures of the clavicle shaft.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 6 - 6
1 Mar 2010
Schemitsch EH
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Purpose: Tibial shaft fractures are a common injury. Tibial nailing is the current standard of care for these injuries, yet there is little information regarding patient based outcomes after nailing. We sought to determine the 1 year patient based outcomes and return to activities for patients with tibia fractures in a randomized trial of reamed and unreamed nail insertion.

Method: Over a 5 year period 1226 patients with 842 closed and 406 open tibial shaft fractures were enrolled in a randomized trial comparing reamed with unreamed tibial nail insertion in 29 trauma centers and had one year follow-up. The average age was 39±16 years and 74% were male. Patient based outcomes were determined using the validated Short Form-36 (SF-36) Physical Component Summary, the Short Musculoskeletal Functional Assessment (SMFA) Dysfunction Index, and a published return to activity questionnaire. Questionnaires were administered during the initial hospitalization to obtain pre-injury status, and then the same outcome instruments were used at the 2 week, 3 month, 6 month, and one year follow-up. Statistical analysis was performed comparing the groups with p < 0.05 designated as significant.

Results: There was no difference in any outcome parameter for any time frame between the reamed and unreamed groups. The 1 year SF-36 PCS (a 100 point scale with a mean of 50 in the general population, higher better) was 42.9±11 for the reamed group and 43.5±11 for unreamed group as compared with 52.5±9 for the reamed group and 53.1±9 for the unreamed group pre-injury. The SMFA Dysfunction Index (100 point scale, higher is worse) at 1 year was 18.2±17 for the reamed group and 17.5±17 for the unreamed group as compared with 7.9±13 for the reamed group and 7.7±13 unreamed group pre-injury.

Conclusion: In patients with tibial shaft fractures treated with intramedullary nails, patient based outcomes are not related to reamed or unreamed insertion. Patients sustaining tibial shaft injuries do not return to their pre-injury status based on validated outcomes assessments or return to activity by one year after injury.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 17 - 17
1 Mar 2010
Li R vonSchroeder HP Stewart DJ Schemitsch EH
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Purpose: Micro-CT is efficient, non-destructive, and accurate for qualitative and quantitative studies of bone microarchitecture during fracture healing. A cell-based vascular endothelial growth factor (VEGF) gene delivery system can increase fracture healing. Three dimensional structural variation of new bone formation in rabbit fracture segmental defects was studied with micro-CT to determine how VEGF affects these microarchitectural differences for bone healing in various periods.

Method: All animal procedures were approved by the Animal Care Committee at St. Michael’s hospital. Ten millimeter segmental bone defects were treated by local injection with cell-based VEGF gene transfer (n=15), or control group with fibroblasts alone or saline only (n=15), to stimulate differences in bone healing. The animals were sacrificed and fracture healing specimens collected at 4, 8 and 12 weeks post surgery. The region of interest (ROI) was set where the segmental defect was located, and was selected for analysis from the recognizable margins of the original defect. To describe the topographic pattern of bone healing, the ROI was divided into three areas of equal volume: proximal, middle and distal. The new bone formation and mineralization at the defect sites were evaluated by bone structural parameters from the 3-D reconstruction of micro-CT.

Results: Macroscopic evaluation of the interfragmentary section from reconstructed micro CT scans, in the VEGF treated rabbits, showed abundant fragmentary bone filling the gap of the osteotomy at 4 weeks and abundant callus bridging the gap at 8 and 12 weeks. In the control group, only small amounts of sparsely formed bone were seen in the gap at 4 weeks. In the control group, the regenerate bone was ovoid around the bone sites and a big gap remained in the segmental bone defects at 8 and 12 weeks. The bone healing micro-structural differences between the two groups varied with the period of treatment, with more differences seen at 4 than 8 or 12 weeks.

Conclusion: Cell-based VEGF gene therapy enhances fracture healing of segmental defects, and this effect is best seen in the early period following defect creation.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 2 - 2
1 Mar 2010
Zdero R Olsen M Elfatori S Skrinskas T Schemitsch EH Whyne C Von Schroeder HP
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Purpose: The mechanical behavior of human scapholunate ligaments is not described well in the literature regarding torsion. Presently, intact scapholunate specimens were mechanically tested in torsion to determine if any tensile forces were generated as a result.

Method: Scapholunate specimens (n=19) were harvested and inspected visually. Scaphoid and lunate bones were potted in square chambers using epoxy cement. The interposing ligaments remained exposed. Specimens were mounted in a specially designed test jig and remained at a fixed axial length during testing. Using angular displacement control, ligaments were subjected to a torsional motion regime that included cyclic preconditioning (25 cycles, 1 Hz, triangular wave, 5 deg max), ramp-up to 15 deg at 180 deg/min, stress relaxation for 120 sec duration, ramp-down to 0 angulation at 180 deg/min, rest period for 5–10 minutes, and torsion-to-failure at 180 deg/min. Torque and axial tension were monitored simultaneously.

Results: Tests showed a coupled linear relationship between applied torsion and the resultant tensile forces generated for the ligament during ramp-up (Torsion/Tension Ratio = 38.86 +/− 29.00 mm, Linearity Coefficient R-squared = 0.89 +/− 0.15, n=19), stress relaxation (Ratio = 23.43 +/− 15.84 mm, R-squared = 0.90 +/− 0.09, n=16), and failure tests (Ratio = 38.81 +/− 26.39 mm, R-squared = 0.77 +/− 0.20, n=16). No statistically significant differences were detected between the Torsion/Tension ratios (p=0.13) or between the linearity (R-squared) of the best-fit lines (p> 0.085).

Conclusion: A strong linear relationship between applied torsion and resulting tensile forces for the ligament was exhibited during all testing phases. This may suggest that there is interplay between torsion and tension in both the stabilization of the scapholunate ligament during normal physiological motion and during resistance to injury processes. This is the first report in the literature of the coupling of torsion with tension for the scapholunate ligament.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 6 - 6
1 Mar 2010
Petrisor B Bhandari M Schemitsch EH Sprague S Sanders D Jeray K Hanson B
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Purpose: The choice of irrigating fluid and delivery pressure remains controversial. Identifying surgeons’ preferences in techniques and the rationale for their choices may aid in focusing educational activities to the orthopaedic community as well as planning future clinical trials. Our objective was to clarify current opinion with regard to the irrigation of open fracture wounds.

Method: We mailed and delivered a cross-sectional survey using a sample-to-redundancy strategy to members of the Canadian Orthopaedic Association and attendees of an international fracture course (AO, Davos, Switzerland) to examine surgeons’ preferences in the initial management of open fracture wounds.

Results: Of the 1,764 surgeons who received the questionnaire, 984 (55.8%) responded. In the management of open wounds, most surgeons surveyed, 676 (70.5%), favoured normal saline alone, however 16.8% used Bacitracin. Many surgeons, 695 (71%) used low pressures when delivering the irrigating solution to the wound, however variation exists in what constituted high versus low pressure lavage. Surgeons supported the need for a clinical trial evaluating outcomes following both the use of different irrigating solutions as well as irrigating pressures [803 (84.8%) and 730 (77.6%) respectively].

Conclusion: The majority of surgeons favour both normal saline and low pressure lavage for the initial management of open fracture wounds.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 1 - 1
1 Mar 2010
Li CH Li R Waddell JP Schemitsch EH
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Purpose: Vascular Endothelial Growth Factor (VEGF) is vital for both angiogenesis and osteogenesis. The aim of this study was to investigate the effect of cell based VEGF gene delivery on the proliferation and mineralization of rabbit osteoblasts in vitro.

Method: Primary cultured rabbit osteoblasts were divided into four groups (each n=6). In Group I, osteoblasts were transfected with pcDNA3.1-VEGF; in Group II, osteoblasts were transfected with pcDNA-Efficiency Green Fluorescent Protein (EGFP); in Group III, osteoblasts were treated with the supernatant of fibroblasts that were transfected with VEGF genes; and in Group IV, osteoblasts were treated with the supernatant of fibroblasts that were transfected with EGFP. The cells were cultured in a-EME with 10% FBS, 2% penicillin/streptomycin with or without 10-^7 M dexamethasone and 50μg/ml L-ascorbic acid for 28 days. In the last 4 days, the cells were stimulated to initiate calcium mineralized nodule formation by adding 10 mM B-glycerophosphate. They were stained by the Von Kossa technique so that the number and the area of the nodules could be assessed by an imaging analysis system.

Results: The cells transfected by VEGF were indicated by the EGFP marked cells under a fluorescent microscope. There was a significant difference in the total nodule area (mean 18.38 mm2 SE 3.73 and 5.07 mm2 SE 0.55, p< 0.05) and count (mean 18.67 SE 3.22 and 2.17 SE 0.40, p< 0.001) between Group I and Group II (ANOVA, SPSS). More unmineralized and smaller nodules were found in Group III and Group IV. However, the nodules in Group III covered greater areas with dark brown staining in the cell culture dishes when compared with Group IV.

Conclusion: The observations indicate that cell based VEGF gene delivery has a positive effect on the proliferation and mineralization of osteoblasts. The greatest effect is seen with direct transfection of osteoblast cells. Cell-based VEGF gene therapy may be used to promote fracture healing.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 7 - 7
1 Mar 2010
Selby R Geerts WH Kreder HJ Crowther MA Bent M Schemitsch EH Weiler P Kaus L Sealey F Jay R
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Purpose: We conducted the first, multicentre, prospective cohort study to define the incidence of symptomatic venous thromboembolism (VTE) in patients with tibia and ankle fractures treated conservatively and relatively minor lower leg fractures. The reported incidence of deep vein thrombosis (DVT) using routine venography in patients with lower leg injury requiring cast immobilization is approximately 20–40%, which has lead to the routine use of anticoagulant prophylaxis for several weeks in many such patients. However the vast majority of venographically-detected DVTs are asymptomatic, distal thrombi whose clinical relevance is uncertain. Therefore venography is not the best outcome measure to assess the burden of clinically important VTE.

Method: Consecutive patients with tibia and fibula fractures (treated non-operatively) and patella and foot fractures, (treated operatively or conservatively) were assessed for eligibility at 5 Ontario hospitals. Patients were enrolled after informed consent within 96 hours of injury and were followed prospectively, by telephone, at 2, 6 and 12 weeks. Those with major trauma, active cancer, and previous VTE were excluded. Thromboprophylaxis was not allowed. Education regarding symptoms of VTE was provided at study entry and patients were asked about VTE symptoms at follow up. Suspected VTE was investigated in a standardized manner.

Results: From August 2002 to June 2005, 1200 patients were enrolled from 2446 consecutively screened patients. 98% of patients completed 3-month follow-up. The mean age was 45 years (16 to 93) and 60% were female. The most common fractures were fibular (39%) and most injuries were caused by falls (75%). 99 % of these fractures were unilateral. Most fractures did not require surgical repair (93%), and 82% of patients were immobilized by cast or splint for an average of 42 ±32 days. Overall, 7 patients had symptomatic, objectively confirmed VTE (2 proximal DVT, 3 calf DVT, 2 PE) with no fatal PE – an incidence of 0.6 % (95% CI 0.2 to 1.2).

Conclusion: Symptomatic VTE is an infrequent complication after these fractures without thromboprophylaxis. Therefore routine thromboprophylaxis is neither warranted, nor likely to be cost-effective in these patients. This study also highlights the significant discrepancy between clinical endpoint studies and studies using venography.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 10 | Pages 1281 - 1286
1 Oct 2009
Olsen M Davis ET Chiu M Gamble P Tumia N Boyle RA Schemitsch EH

The computed neck-shaft angle and the size of the femoral component were recorded in 100 consecutive hip resurfacings using imageless computer-navigation and compared with the angle measured before operation and with actual component implanted. The reliability of the registration was further analysed using ten cadaver femora. The mean absolute difference between the measured and navigated neck-shaft angle was 16.3° (0° to 52°). Navigation underestimated the measured neck-shaft angle in 38 patients and the correct implant size in 11. Registration of the cadaver femora tended to overestimate the correct implant size and provided a low level of repeatability in computing the neck-shaft angle.

Prudent pre-operative planning is advisable for use in conjunction with imageless navigation since misleading information may be registered intraoperatively, which could lead to inappropriate sizing and positioning of the femoral component in hip resurfacing.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 255 - 255
1 May 2009
Schemitsch EH Zdero R
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Femur fractures are a complication of hip arthroplasty. When the stem is well fixed, fracture fixation is the preferred treatment option. Numerous fixation methods have been advocated, using plates and/or allograft struts. The study was conducted to determine the biomechanical characteristics of three constructs currently used for fixation of these fractures.

Vancouver type B1 periprosthetic femur fractures were created distal to a cemented hip stem implanted in third generation composite femurs. The fractures were fixed with one of three constructs: 1- A non-locking plate and allograft strut (NLP-A) 2- A locking plate and allograft strut (LP-A) 3- A locking plate alone. (LP) The struts were held in place with cables. There were five specimens in each group. Following fixation, the constructs underwent sinusoidal cyclic loading from 200 to 1200 N for 100000 cycles. Stiffness of the constructs was determined in bending, torsion and axial compression before and after cyclic loading. Axial load to failure was also determined.

Overall, cyclic loading had little effect on the mechanical properties of these constructs. The two constructs with allografts were significantly stiffer in coronal plane bending than the construct consisting of only a locking plate. There were no significant differences in axial or torsional stiffness between the constructs. Load to failure of the NLP-A (4095 N) and LP-A (4007 N) constructs was significantly greater than the LP construct (3398 N) (p=0.023 and p=0.044 respectively).

All three constructs tested retained their mechanical characteristics following 100000 cycles of loading. Our initial concerns that the cables holding the allograft strut would loosen appear unfounded. Allograft strut-plate constructs are stiffer in bending and have a higher load to failure than a stand-alone locking plate. When an allograft plate construct is chosen, locking screws provide no mechanical advantage in this experimental model.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 253 - 253
1 May 2009
Haydon CM Bukczynski J Nousiainen M Schemitsch EH Stephen D Wadell JP
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Early fracture stabilization has been shown to reduce morbidity and mortality in the patient who is multiply injured. Controversy exists in terms of managing multiple trauma patients who sustain thoracic injuries along with femoral shaft fractures. The purpose of the present study was to determine whether the presence and treatment of femoral shaft fractures increases morbidity in patients with pulmonary contusions and to determine the effect of patient and surgical factors on outcome.

Patients that suffered chest injuries between January 1987 and April 2006 were identified from the prospectively collected trauma databases at two hospitals. Patient records were reviewed to verify all data. The diagnosis of pulmonary contusion was confirmed with radiologic or post-mortem investigations. All relevant patient and surgical data was collected. Exclusion criteria included severely injured patients (head/abdomen AIS> 3), age sixty years, death twenty-four hours after injuries occurred.

A total of 1190 patients with confirmed pulmonary contusions met inclusion criteria; there were 113 femoral shaft fractures (five bilateral). Patients in both the isolated pulmonary contusion and pulmonary contusion with femoral fracture had similar injury severity scores (ISS) and demographic information. Fractures were reduced with intramedullary nailing in 88% of cases. Mean age was thirty-five years. There were significantly more incidences of fat embolism syndrome and acute lung injury (ALI) in patients with femoral factures (twenty-four hours following the injury had significantly greater risk of developing ARDS (p< 0.05).

The presence of femoral shaft fractures in patients with pulmonary contusions increases the duration of admittance to hospital and can lead to higher rates of fat embolism syndrome and ALI, however it does not appear to impact overall mortality or contribute to the development of other common respiratory complications. Early reduction of shaft fractures is encouraged to further decrease complications.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 254 - 254
1 May 2009
Bederman SS McKee MD Schemitsch EH Bhandari M
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Fat embolism syndrome (FES) is a potentially lethal condition commonly seen in poly-traumatised patients, particularly those with multiple long-bone fractures. Treatment has centered around supportive care and early fracture fixation. Several clinical small trials have suggested corticosteroids benefit patients with FES but its use remains controversial. Our objective was to determine the effect of corticosteroids in preventing FES in patients with multiple long-bone fractures.

We conducted a meta-analysis of randomised trials, searching computerised databases for published studies from 1966–2006. Additionally, we performed hand searches of major orthopaedic journals, meeting proceedings, and texts. Our primary outcome was the rate of FES. Secondary outcomes included presence of hypoxia, petechiae, mortality, infection, and delayed union.

Of the one hundred and four studies identified, nine were potentially eligible, and only seven met all our eligibility criteria. From our pooled analysis of three hundred and eighty-nine patients, we found that corticosteroids reduced the risk of FES by 78% (95%CI: 43–92%, heterogeneity p-value=0.62, I2=10%) and that only eight patients needed to be treated (NNT=7.5) to prevent one case of FES (95%CI: five to thirteen patients). We did not find any significant differences in the rates of mortality, infection, or delayed union.

The current evidence suggests that the use of corticosteroids is beneficial in the prevention of fat embolism syndrome in patients with multiple long-bone fractures. The use of corticosteroids does not appear to significantly increase the risk of complications although a confirmatory large randomised trial is needed.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 218 - 218
1 May 2009
Li R Schemitsch EH Stewart DJ von Schroeder HP
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We sought to establish whether fibroblasts transfected ex vivo could be delivered via gelfoam impregnated with a solution of transfected cells to achieve local transgene expression in a fracture site.

A 10 millimeter segmental bone defect was created after 12 mm periosteal excision and plated in the middle one third of each rabbit tibia. Dermal tissues were obtained and fibroblasts were cultured with DMEM. Fibroblasts were labeled with CMTMR and 5x106 labeled fibroblasts in 1ml PBS with 1x1 cm? Impregnated gelfoam was placed into the fracture gap (n=2). Twenty four hours after cell injection, the rabbits were killed and specimens were harvested from the fractured leg. Using SuperFect (Qiagen Inc), the primary fibroblasts were transfected with pcDNA-VEGF which was generated with the full length coding sequence of the human VEGF gene. A convenient reporter gene, Efficiency Green Fluorescent Protein (EGFP), was used for monitoring transfection of VEGF by fluorescence intensity. Experimental rabbits received 5.0 X 106 VEGF transfected cells in 1 ml PBS via gelfoam at the fracture sites. The animals were sacrificed at seven days (n=4), fourteen days (n=4) and twenty-one days (n=4) post surgery and the fracture site specimens were collected for analysis.

The fluorescently labeled cells with CMTMR were found at the fracture site and surrounding tissues. It was demonstrated that the labeled cells were delivered into the fracture gap, bone marrow and muscle surrounding a segmental defect in the rabbit. In the VEGF group, visualised VEGF immunostaining (brown) was shown in the fracture site around the Gelfoam; as well VEGF was distributed at sites of endochondral ossification. Visible bone formation was shown: VEGF promoted new bone formation by VonKossa staining (dark) and produced numerous vessels by CD31 positive staining (brownish black). The VEGF protein was detected in and around the fracture by ELISA.

This data encourages the further development of genetic approaches using cell based VEGF gene transfer without viral vectors to promote fracture healing.