Osteoarthritis (OA) is the most common form of arthritis and one of the ten most disabling diseases in developed countries. Total joint replacement (TJR) is considered by far as the most effective treatment for end-stage OA patients. The majority of patients achieve symptomatic improvement following TJR. However, about 22% of the TJR patients either do not improve or deteriorate after surgery. Several potential non-genetic predictors for the TJR outcome have been investigated. However, the results were either inconclusive or had very limited predictive power. The aim of this study was to identify genetic variants for the poor outcome of TJR in primary OA patients by a genome-wide association study (GWAS).

Study participants were total knee or hip replacement patients due to primary OA who were recruited to the Newfoundland Osteoarthritis Study (NFOAS) before 2017. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess pain and functional impairment pre- and 3.99±1.38 years post-surgery. Two non-responder classification criteria were used in our study. One was defined by an absolute WOMAC change score. Participants with a change score less than 7/20 points for pain were considered as pain non-responders; and those with less than 22/68 points for function were classified as function non-responders. The second one was the Outcome Measures in Arthritis Clinical Trials and the Osteoarthritis Research Society International (OMERACT-OARSI) criteria. Blood DNA samples were genotyped using the Illumina GWAS microarrays genotyping platform. The quality control (QC) filtering was performed on GWAS data before the association of the genetic variants with non-responders to TJR was tested using the GenABEL package in R with adjustment for the relatedness of the study population and using the commonly accepted GWAS significance threshold p < 5*10⁻⁸ to control multiple testing.

In total, 316 knee and 122 hip OA patients (mean age 65.45±7.62 years, and 58% females) passed the QC check. These study participants included 368 responders and 56 non-responders to pain, and 364 responders and 68 non-responders to function based on the absolute WOMAC point score change classification. While 377 responders and 56 non-responders to pain, and 366 responders and 71 non-responders to function were identified by the OMERACT-OARSI classification criteria. Interestingly, the same results were obtained by both classification methods, and we found that the G allele of rs4797006 was significantly associated with pain non-responders with odds ratio (OR) of 5.12 (p<7.27×10^-10). This SNP is in intron one of the melanocortin receptor 5 (MC5R) gene on chr18. This gene plays central roles in immune response, pain sensitivity, and negative regulation of inflammatory response to antigenic stimulus. The A allele of rs200752023 was associated with function non-responders with OR of 4.41 (p<3.29×10^-8). The SNP is located in intron three of the RNA Binding Fox-1 Homolog 3 (RBFOX3) gene on chr17 which has been associated with numerous neurological disorders.

Our data suggested that two chromosomal regions are associated with TJR poor outcomes and could be the novel targets for developing strategies to improve the outcome of the TJR.

Total joint replacement (TJR) is by far the most effective therapy for end-stage OA patients. Most of patients achieve joint pain reduction and function improvement following to TJR, however up to 22% of them either do not improve or deteriorate after surgery. The aim of this study was to identify genetic variants to be associated with poor outcome of TJR in primary OA patients by a genome-wide association approach (GWAS).

Study participants were primary OA patients from the Newfoundland Osteoarthritis Study (NFOAS) that comprised total knee or hip replacement and recruited before 2016 in St. John's, NL. DNA samples were extracted from patients' blood. Study participants completed their pre-operation and 3.99±1.38 years post-surgery outcome assessment using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). DNA samples were genotyped using the genome-wide Illumina HumanOmni2.58 genotyping microarray containing 2.4 million SNPs. Pre-association quality control filtering was conducted for the raw genotyping data using PLINK 1.7 program, and genotype imputation was performed using the IMPUTE2 algorithm with multiple population reference data from 1000 Genome Project. The imputed data with ∼3.1 million variants was used to test the association with non-responders to TJR using the additive genetic model.

Eighty three primary OA patients (44 responders and 39 non-responders) were included in the analysis. Association analysis detected three chromosomal regions on chr5, 7, and 8 to be significantly associated with non-responding to pain. The top SNPs at these loci are intergenic variants that include SNP (rs17118094, p=4.4×10-5) on chr5. This SNP is adjacent to SGCD gene that plays an important role in muscular strength and maintenance. Another associated SNP (rs71572810, p=4.7×10-5) is nearby IMMP2L gene on chr7. This gene is reported to be associated with behavioral abnormalities. Finally, SNP (rs6992938, p=5.8×10-5) on chr8 is located downstream of TRPA1 gene that is known to have a central role in the pain response to endogenous inflammatory mediators. Three loci were also found to be significantly associated with non-responding to function. The lead variant in the locus on chr1 is an intergenic SNP (rs9729377, p=1.7×10-5) falling between CTBS and MCOLN2 genes. CTBS gene is associated with TNF-α, a cytokine that stimulate the inflammation acute phase reaction, and MCOLN2 gene plays a role in the chemokine secretion and macrophage migration in the innate immune response. Other top SNPs in loci on chr2 and 10 harbor CCDC93, INSIG2, and KLF6 genes that are associated with heel bone mineral density, hypercholesterolemia, obesity and BMI.

To our knowledge, this project is the first study that investigated the association between genetic factors and TJR non-responders. Our results demonstrated that genes related to muscle strength, behavioral trait, pain response, and inflammation play a significant role in poor outcome of TJR, warranting further investigation.

While total joint replacement (TJR) is considered as an effective intervention to relieve pain and restore joint function for end-stage osteoarthritis (OA) patients, a significant proportion of the patients are dissatisfied with their surgery outcomes. The aim of this study was to identify genetic factors that can predict patients who do or do not benefit from these surgical procedures by a genome-wide association study (GWAS).

Study participants were derived from the Newfoundland Osteoarthritis Study (NFOAS) which consisted of 1086 TJR patients. Non-responders to TJR was defined as patients who did not reach the minimum clinically important difference (MCID) based on the self administered Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in terms of pain reduction or function improvment. DNA was extracted from the blood samples of the study participants and genotyped by Illumina GWAS genotyping platform. Over two million single nucleotide polymorphisms (SNPs) across the genome were genotyped and tested for assocition with non-responders.

39 non-responders and 44 age, sex, and BMI matched responders were included in this study. Four chromosome regions on chromosomes 5, 7, 8, and 12 were suggested to be associated with non-responders with p < 1 0–5. The most promising one was on chromosome 5 with the lead SNP rs17118094 (p=1.7×10–6) which can classify 72% of non-responders accurately. The discriminatory power of this SNP alone is very promising as indicated by an area under the curve (AUC) of 0.72 with 95% confidence interval of 0.63 to 0.81, which is much better than any previously studied predictors mentioned above. All the patients who carry two copies of the G allele (minor allele) of rs17118094 were non-responders and 75% of those who carry one copy of the G allele were non-responders. The discriminatory ability of the lead SNPs on chromosomes 7 and 12 were comparable to the one on chromosome 5 with an AUC of 0.74, and 88% of patients who carry two copies of the A allele of rs10244798 on chromosome 7 were non-responders. Similarly, 88% of patients who carry two copies of the C allele of rs10773476 on chromosome 12 were non-responders. While the discriminatory ability of rs9643244 on chromosome 8 was poor with an AUC of 0.26, its strong association with non-responders warrants a further investigation in the region.

The study identified four genomic regions harboring genetic factors for non-responders to TJR. The lead SNPs in those regions have great discriminatory ability to predict non-responders and could be used to create a genetic prediction model for clinical unitilty and application.

Total hip arthroplasty (THA) is a common and extremely beneficial procedure that is being performed more often as the population ages. Current THA follow-up guidelines require large amounts of resources and may not justify their cost with increased patient outcomes. Most problems that would require THA revision will cause symptoms. Late-presenting asymptomatic THAs that are found to require revision are complicated and expensive to address and often lead to poor patient outcomes. Follow-up visits for THA patients are essentially a screening tool to identify asymptomatic THAs that require revision. The rate of asymptomatic THA revision and the subsequent cost of screening for them is not well reported in the literature. Given the relative shortage of orthopaedic resources, efficient use of clinic time should be a priority and inefficient practices should be identified and changed.

We calculated the rate of asymptomatic hip revisions over the first twenty years of THA ownership. We further calculated the cost of a single visit to the orthopaedic clinic for follow up of a THA. Finally, we calculated the cost savings of decreasing the follow-up schedule to a total of three visits.

The cost savings of foregoing the screening to identify one asymptomatic THA requiring revision is CAD $1.2 million.

Asymptomatic THAs requiring revision are rare and, as such, require a large amount of follow up to diagnose. As a screening tool, regular orthopaedic follow up of THA is an inefficient use of resources. Current follow-up guidelines are cost-prohibitive and should be made much less frequent in order to save resources.

Purpose

On January 12th, 2010 a magnitude 7.0 earthquake struck the downtown area of Port au Prince, the capital of the poorest country in the western world. Nearly a quarter of a million people were killed and a million other were injured. Our goal was to provide follow up and acute care to injured Haitain patients.

Purpose: The purpose of this study is to evaluate the hemodynamic and pulmonary effects of intramedullary nailing with a removable filter placed into the common iliac vein.

Methods: Under general anaesthesia, a collapsible filter was inserted into the left common iliac vein in eight dogs and compared to a control group from a previous study. The left femora and tibiae were then pressurized by injection of bone cement and the insertion of intramedullary rods. Echocardiographic images and hemodynamic measurements including arterial blood gas, cardiac output, left atrial, right atrial, pulmonary arterial, and aortic pressure were recorded as baseline measurements and at 1, 5 and 15 minutes after medullary-canal pressurization. After fifteen minutes of pressurization the filter debris was evacuated, the samples sent for analysis and the filter was collapsed and removed. The dog’s hemodynamics were then monitored for a further fifteen minutes. The animals were killed and the lungs were harvested for histomorphometric analysis.

Results: Full hemodynamic and histomorphometric results of the lung tissue and debris collected from the evacuated filters are still pending at the time of this submission however initial findings indicate that the filter prevented an immediate increase in mean pulmonary artery pressure after canal pressurization. No large embolic event was visualized in any of the filtered dogs. In contrast, all animals in the control group demonstrated moderate-to-severe echogenic response with intense showering of echogenic material, including large embolic masses. Removal of the filter was safe and repeatable.

Conclusions: This experiment has shown that proximal venous blockade by means of a removable filter was able to reduce the size and the quantity of the embolic load on the lungs and the filter could be safely collapsed and removed after suctioning of the debris. High rates of embolization causing increased morbidity and mortality after intramedullary stabilization of pathological fractures and of traumatic fractures with concomitant lung injury have been reported. Prophylactic insertion of a removable temporary filter in this high-risk group prior to reamed intramedullary nailing may be beneficial.

Funding : Other Education Grant

Funding Parties : Synthes Canada

Wrong site surgery is a preventable problem. In 1994 the Canadian Orthopaedic Association (COA) began an educational program initiated to prevent such mistakes from occurring. The purpose of this study was to assess the proportion of orthopedic surgeons who mark their sites preoperatively. This study confirms a high proportion (74.9%) of surgeons in Canada follow the COA guidelines at least occasionally with over half (52.1%) consistently “signing their sites.”

Wrong site surgery is often a catastrophic, but preventable problem. Reports of wrong site surgery have been on the rise in the United States every year since 1995. In 1994 the Canadian Orthopaedic Association (COA) began an educational program initiated to prevent such mistakes from occurring. Their recommendations involved marking the incision site preoperatively. Since that time the claims of wrong site orthopedic surgery have diminished. The purpose of this study was to assess the proportion of orthopedic surgeons who mark their sites preoperatively.

Two hundred orthopedic surgeons across Canada were asked to complete a survey concerning preoperative incision site marking.

A response rate of 89.3% was achieved. Eighty seven (52.1%) stated they always marked their incision site, thirty eight (22.8%) stated they occasionally marked their incision site, while forty two (25.1%) claimed to never mark their incision site preoperatively. Surgeons in academic centers were more likely to sign their sites than their community counterparts (p=0.021) and surgeons in practice longer were less likely to comply with the COA recommendation (p=0.023).

The COA and American Academy of Orthopedic Surgeons (AAOS) have recommended marking incision sites preoperatively in an attempt to reduce wrong site surgery. This study confirms a high proportion (74.9%) of surgeons in Canada follow the COA guidelines at least occasionally with over half (52.1%) consistently “signing their sites.”