The Use of Biomarkers to Quantify Clinical Response to Total Knee Arthroplasty Interventions: A Systematic Review.

The primary objective of this review was to determine whether the attenuation of the postoperative inflammatory response (PIR) after total knee arthroplasty (TKA) leads to a notable improvement in clinical outcome scores. The secondary objective of this review was to determine the optimal approach in using inflammatory biomarkers, clinical inflammatory assessments, and imaging to quantify the PIR. A systematic literature search of eight major databases was conducted using a predetermined search strategy. C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), knee surface temperature (KST), and clinical outcome data were collected and graphically displayed. Eighty-six percent of the studies that reported a statistically significant decrease in inflammatory biomarkers in their treatment group demonstrated a concordant notable improvement in clinical outcome scores. Mean CRP, IL-6, ESR, and KST values peaked on postoperative day (POD) 2, POD1, POD7, and POD 1-3, respectively. The PIR is correlated with early pain and function recovery outcomes. Future studies comparing TKA surgical methodologies and perioperative protocols should assess PIR by incorporating inflammatory biomarkers, such as CRP and IL-6, and clinical inflammatory assessment adjuncts, to provide a more comprehensive comparison.

Femoral internal torsion greater than twenty-five degrees and/or external tibial torsion greater than thirty degrees as measured by computed tomography are threshold values for axial alignment correction in patellofemoral instability.

OBJECTIVES: Patellofemoral instability (PFI) has multiple predisposing anatomic factors, including ligamentous hyperlaxity, coronal and axial malalignment, patella alta, trochlea dysplasia, excessive lateral patellar tilt, and excessive lateral Q vector. Yet, few studies have analyzed surgical thresholds for performing axial alignment corrective osteotomies in the treatment of PFI and patella maltracking. The objective of this systematic literature review was to determine if there is a threshold for axial plane alignment that triggers surgical correction for the treatment of patellar instability in the published literature. METHODS: Using a predetermined search strategy, a systematic literature search of 10 major databases and gray literature resources was completed. Only studies reporting on patellar instability and outcomes were included. Radiologic indications, additional procedures, outcomes, and complications were reported. Titles and abstracts were screened, and full-text manuscripts were then selected and extracted. Variables related to radiographic and clinical parameters, patient demographics, surgery performed, surgical correction, complications, and reoperations were recorded preoperatively and postoperatively. RESULTS: A total of 1132 abstracts and titles were screened by two reviewers, yielding 15 eligible studies. The reported threshold identified in our study for axial plane alignment that triggers surgical correction in most of the published literature when discussing PFI was either tibial torsion greater than 30° and/or femoral anteversion greater than 25°. Following rotational osteotomy of one or both long bones, one study (7%) reported improvements in tubercle-sulcus angle, two studies (13%) reported improvements in femoral-tibial angle, and four studies (27%) reported decreases in tibial torsion. For patient-reported outcomes, seven studies (47%) reported improvement in the Kujala score, five studies (33%) reported postoperative improvement in Lysholm, and four studies (27%) reported improvement in the International Knee Documentation Committee (IKDC) score. Nine studies (60%) reported preoperative femoral anteversion; however, only two studies compared pre- and post-operative values (one study reported a decrease in anteversion and another study reported an increase in anteversion). CONCLUSION: When treating PFI, the reported threshold for axial plane alignment that triggers surgical correction in most of the published literature was tibial torsion greater than 30° and/or femoral anteversion greater than 25° as measured by CT. However, there is no consensus on the axial alignment measurement technique. LEVEL OF EVIDENCE: III.

Major complications after total hip arthroplasty with the direct anterior approach at a high-volume Ontario tertiary care centre.

BACKGROUND: The rate of major surgical complications for high-volume orthopedic surgeons using the direct anterior approach (DAA) in Ontario, Canada, is not known. The purpose of this study was to investigate the rate of major surgical complications after total hip arthroplasty (THA) using DAA performed by experienced orthopedic surgeons at a high-volume tertiary care centre in Ontario. METHODS: We conducted a retrospective cohort review of primary THA through DAA performed by 2 experienced fellowship-trained surgeons at an academic hospital in London, Ontario, between Jan. 1, 2012, and May 1, 2019. We excluded the first 100 cases to allow for surgeon learning curves. We recorded major surgical complications (intraoperative events, postoperative periprosthetic fractures, dislocation requiring closed or open reduction, implant failure [aseptic loosening or subsidence], early (< 6 wk) deep wound infection requiring irrigation and débridement, late (≥ 6 wk) deep wound infection requiring irrigation and débridement, and wound complications [wound dehiscence, stitch abscess, erythema, hematoma or seroma]) within 1 year of THA. RESULTS: A total of 875 primary DAA THA procedures were included. The rates of surgical complications were 0.9% for intraoperative events, 1.5% for postoperative periprosthetic fractures, 0.8% for implant failure, 0.7% for early deep wound infection, 0.1% for late deep wound infection and 3.2% for wound complications; there were no cases of dislocation. The rate of revision for implant failure within 1 year was 0.1%. Male sex was associated with a greater risk of implant failure (p = 0.01), and having a higher body mass index was associated with both increased rates of infection (p < 0.01) and having a wound complication (p < 0.01). CONCLUSION: Intraoperative events, postoperative periprosthetic fractures, implant failure, deep wound infection and wound complications accounted for the major surgical complications within 1 year of THA through DAA. The low revision rate suggests that DAA is a safe approach for THA.

Structural Consequences of a Partial Anterior Cruciate Ligament Injury on Remaining Joint Integrity: Evidence for Ligament and Bone Changes Over Time in an Ovine Model.

BACKGROUND: Severe injury to the knee joint often results in accelerated posttraumatic osteoarthritis (PTOA). In an ovine knee injury model, altered kinematics and degradation of the cartilage have been observed at 20 and 40 weeks after partial anterior cruciate ligament (ACL) transection (p-ACL Tx) surgery. However, changes to the integrity of the remaining intact intra-articular ligaments (posterolateral [PL] band and posterior cruciate ligament [PCL]) as well as the subchondral bone after anteromedial (AM) band Tx remain to be characterized. PURPOSE: (1) To investigate histological alterations to the remaining intact intra-articular ligaments, the synovium, and the infrapatellar fat pad (IPFP) and (2) to quantify subchondral bone changes at the contact surfaces of the proximal tibia at 20 and 40 weeks after AM band Tx. STUDY DESIGN: Descriptive laboratory study. METHODS: Mature female Suffolk cross sheep were allocated into 3 groups: nonoperative controls (n = 6), 20 weeks after partial ACL transection (p-ACL Tx; n = 5), and 40 weeks after p-ACL Tx (n = 6). Ligament, synovium, and IPFP sections were stained and graded. Tibial subchondral bone microarchitecture was assessed using high-resolution peripheral quantitative computed tomography. RESULTS: p-ACL Tx of the AM band led to significant change in histological scores of the PL band and the PCL at 20 weeks after p-ACL Tx (P = .031 and P = .033, respectively) and 40 weeks after p-ACL Tx (P = .011 and P = .029) as compared with nonoperative controls. Alterations in inflammatory cells and collagen fiber orientation contributed to the greatest extent of the combined histological score in the PL band and PCL. p-ACL Tx did not lead to chronic activation of the synovium or IPFP. Trabecular bone mineral density was strongly inversely correlated with combined gross morphological damage in the top and middle layers of the subchondral bone in the lateral tibial plateau for animals at 40 weeks after p-ACL Tx. CONCLUSION: p-ACL Tx influences the integrity (biology and structure) of remaining intact intra-articular ligaments and bone microarchitecture in a partial knee injury ovine model. CLINICAL RELEVANCE: p-ACL Tx leads to alterations in structural integrity of the remaining intact ligaments and degenerative changes in the trabecular bone mineral density, which may be detrimental to the injured athlete's knee joint in the long term.

Methylprednisolone acetate mitigates IL1ß induced changes in matrix metalloproteinase gene expression in skeletally immature ovine explant knee tissues.

OBJECTIVE AND DESIGN: This study aimed at evaluating the effect of methylprednisolone (MPA) on messenger ribonucleic acid (mRNA) expression levels in immature ovine knee joint tissue explants following interleukin (IL)1ß induction and to assess responsiveness of the explants. MATERIAL OR SUBJECTS: Explants were harvested from the articular cartilage, synovium, and infrapatellar fat pad (IPFP) from immature female sheep. TREATMENT: Methylprednisolone. METHODS: The samples were allocated into six groups: (1) control, (2) MPA (10-3 M), (3) MPA (10-4 M), (4) IL1ß, (5) IL1ß + 10-3 M MPA, or (6) IL1ß + 10-4 M MPA. mRNA expression levels for molecules relevant to inflammation, cartilage degradation/anabolism, activation of innate immunity, and adipose tissue/hormones were quantified. Fold changes with MPA treatment were compared via the comparative CT method. RESULTS: Methylprednisolone treatment significantly suppressed MMPs consistently across the cartilage (MMP1, MMP3, and MMP13), synovium (MMP1 and MMP3), and IPFP (MMP13) (all p < 0.05). Other genes that were less consistently suppressed include endogenous IL1ß (cartilage) and IL6 (IPFP) (all p < 0.05), and others not affected either by IL-1 exposure or subsequent MPA include TGFß1, TLR4, and adipose-related molecules. CONCLUSIONS: Methylprednisolone significantly mitigated IL1ß induced mRNA expression for MMPs in the immature cartilage, synovium, and IPFP, but the extent of the responsiveness was tissue-, location-, and gene-specific.

Five- and six-strand hamstring grafts consistently produce appropriate graft diameters for anterior cruciate ligament reconstruction.

PURPOSE: Hamstring tendon graft diameter less than 8 mm has been correlated with an increased risk of anterior cruciate ligament reconstruction (ACLR) graft failure. The purpose of this study was to measure and compare the diameter of 3-, 4-, 5-, and 6-strand gracilis and semitendinosus (ST) hamstring tendon (HT) ACLR grafts, and to determine if there is a correlation between anthropometric data, HT length, and diameter of the HT ACLR graft. METHODS: Male patients (n = 78) undergoing primary or revision ACLR with a HT autograft between July 2018 and March 2020 were recruited. Pre-operative anthropometric data was collected. Gracilis and ST tendons were harvested and the length and diameter measured. The following HT graft configurations were prepared in each patient: triple ST; double gracilis + double ST; double gracilis + triple ST; triple gracilis + triple ST. Paired t-tests and Pearson's correlation coefficients were used to assess demographics, anthropometrics, graft diameter, and tendon length. A non-parametric test was used to compare femoral and tibial ACL graft diameters of the 3-, 4-, 5-, and 6-strand HT graft configurations. RESULTS: For the femoral end, 10%, 19%, 69% and 86% of the patients achieved graft diameters of equal to or greater than 8 mm in 3-, 4-, 5- and 6-strand HT graft configurations respectively. For the tibial end, 27%, 10%, 83%, and 92% of the patients achieved graft diameters of equal to or greater than 8 mm in 3-, 4-, 5-, and 6-strand HT graft configurations respectively. The largest increases in HT graft diameters were noted between the femoral end of 6- vs. 3-strand grafts (mean difference 1.7 ± 0.5 mm; p < 0.001) and between the tibial end of 6- vs. 4-strand grafts (mean difference 2.0 ± 0.5 mm; p < 0.001). Height and leg length were moderately positively correlated with ST tendon length (r = 0.54-0.51) and gracilis tendon length (r = 0.52-0.45), and thigh and shank lengths were moderately positively correlated with ST tendon length (r = 0.43 and 0.40, respectively). CONCLUSION: Traditional 4-strand HT ACL autografts in male patients undergoing ACLR in the United Arab Emirates result in graft diameters less than 8 mm in the majority of patients. LEVEL OF EVIDENCE: III.

Communication in surgical decision-making while managing metastatic bone disease: matching patient expectations with surgical goals.

BACKGROUND: There is a paucity of research examining how surgical decision-making for metastatic bone disease (MBD) can be optimized to improve quality of life (QOL) and functional outcomes, while accurately aligning with patient goals and expectations. The objective of this study was to survey and interview patients with MBD and support persons (PS), physicians, and allied health care providers (HCP) with the goal of identifying (1) important surgical issues related to MBD management, (2) discordance in perioperative expectations, and (3) perceived measures of success in the surgical management of MBD. METHODS: Utilizing a custom survey developed by HCP and patients with MBD, participants were asked to (1) identify important issues related to MBD management, (2) rank perceived measures of success, and (3) answer open-ended questions pertaining to the management of MBD. RESULTS: From the survey, increased life expectancy, minimizing disease progression, removal of local tumour, timely surgery after diagnosis, increased length of hospitalization, and physiotherapy access were all identified as significant discordant goals between PS and physicians/HCP. Conversely, there was an agreement between physicians and HCP who considered improved QOL and functional outcomes as most important goals. Structured homogenous-group workshops identified the need for (1) improved discussions of prognosis, surgical options, expectations, timelines, and resources, (2) the use of a care team "quarterback", and (3) an increased use of multi-disciplinary treatment planning. CONCLUSIONS: We feel this data highlights the importance of improved communication and coordination in treating patients with MBD. Further research evaluating how surgical techniques influence survival and disease progression in MBD is highly relevant and important to patients.

Molecular Response of Rabbit Menisci to Surgically Induced Hemarthrosis and a Single Intra-Articular Dexamethasone Treatment.

Anterior cruciate ligament reconstructive surgery can restore biomechanical stability, however, such surgery cannot reliably prevent the onset of post-traumatic osteoarthritis. The aim of this study was to elucidate the molecular response that occurs within the menisci following a surgical injury that allows bleeding into the joint space, and then to investigate the effect of dexamethasone (DEX) on this molecular response. Cell viability studies following acute controlled exposure to blood and blood plus DEX were also conducted. Forty-eight New Zealand white rabbits were randomly allocated into control, sham, surgical, and surgical + DEX groups (each group n = 6). Animals were sacrificed at 48 h and 9 weeks, and menisci were harvested. The messenger RNA (mRNA) expression levels for key inflammatory, and degradative proteins, as well as mRNA levels for autophagy pathway molecules were quantified, and statistically significant changes were described. Meniscal cell viability was calculated by incubating groups of medial and lateral menisci in autologous blood, or autologous blood plus DEX for 48 h (each group n = 4; total of eight medial and eight lateral menisci), and then conducting a histological live/dead assay. Results indicated a significant reduction in only medial meniscal cell viability when the tissue was exposed to blood in combination with DEX. A single administration of DEX following surgery significantly suppresses the elevated molecular expression for key inflammatory and degradative markers within menisci at 48 h and 9 weeks post-surgery. In vitro, autologous blood did not affect cell viability, but addition of DEX uniquely impacted the medial menisci. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2043-2052, 2019.

Three-dimensional in vivo kinematics and finite helical axis variables of the ovine stifle joint following partial anterior cruciate ligament transection.

Partial anterior cruciate ligament (p-ACL) rupture is a common injury, but the impact of a p-ACL injury on in vivo joint kinematics has yet to be determined in an animal model. The in vivo kinematics of the ovine stifle joint were assessed during 'normal' gait, and at 20 and 40 weeks after p-ACL transection (Tx). Gross morphological scoring of the knee was conducted. p-ACL Tx creates significant progressive post-traumatic osteoarthritis (PTOA)-like damage by 40 weeks. Statistically significant increases for flexion angles at hoof-strike (HS) and mid-stance (MST) were seen at 20 weeks post p-ACL Tx and the HS and hoof-off (HO) points at 40 weeks post p-ACL-Tx, therefore increased flexion angles occurred during stance phase. Statistically significant increases in posterior tibial shift at the mid-flexion (MF) and mid-extension (ME) points were seen during the swing phase of the gait cycle at 40 weeks post p-ACL Tx. Correlation analysis showed a strong and significant correlation between kinematic changes (instabilities) and gross morphological score in the inferior-superior direction at 40 weeks post p-ACL Tx at MST, HO, and MF. Further, there was a significant correlation between change in gross morphological combined score (ΔGCS) and the change in location of the helical axis in the anterior direction (ΔsAP) after p-ACL Tx for all points analyzed through the gait cycle. This study quantified in vivo joint kinematics before and after p-ACL Tx knee injury during gait, and demonstrated that a p-ACL knee injury leads to both PTOA-like damage and kinematic changes.

Alterations in Joint Angular Velocity Following Traumatic Knee Injury in Ovine Models.

Little effort has been directed towards the consequence of an injury on joint angular velocity. We hypothesized that the magnitude of knee joint angular velocity would be decreased after injury. Four injury groups were investigated in an ovine model: (1) anterior cruciate ligament (ACL) and medial collateral ligament (MCL) transection (ACL/MCL Tx) (n = 5), (2) lateral meniscectomy (Mx) (n = 5), (3) partial ACL transection (p-ACL Tx) (n = 5), and (4) partial-ACL and MCL transection (p-ACL/MCL Tx) (n = 5). The magnitude of the angular velocities decreased in the subjects of all groups at multiple points of the gait cycle. The maximum angular velocities during stance and the maximum extension angular velocities during swing were decreased in 15/20 and 17/20 subjects, respectively. There were strong correlations between morphological osteoarthritis scores and the reduction in the maximum extension angular velocities during swing 40 weeks post-p-ACL Tx and 20 weeks post-ACL/MCL Tx. There was no correlation between the decrease of the angular velocity and morphological osteoarthritis scores in the Mx group and the p-ACL/MCL Tx group. The reduction in angular velocity may be a helpful addition as a surrogate measure of OA risk after ACL injury, and could have clinical significance after further investigation in humans.

Newsletter 2018: Clinician Investigator Trainee Association of Canada (CITAC).

Message from the President: Optimism for the Future The Clinician-Investigator Trainee Association of Canada (CITAC) was established in 2006 to address issues relevant to Canadian trainees seeking dual training in medicine and research. As clinician-investigator (CI) trainees, we comprise but a fraction (less than 5%) of all medical trainees. Our 'bilingual' careers render our individual paths less straightforward and more challenging. As a community, we have had to confront several disappointments, perhaps most notably the cessation of funding support for MD/PhD programs in 2015, previously offered by the Canadian Institutes of Health Research (CIHR). Despite these individual and collective challenges, I remain optimistic and incredibly excited about our future. In my own work, I am reminded constantly that being trusted with the dual responsibility of patient care and innovation in medicine is a privilege to be cherished, rather than a burden to be feared. That which makes our path doubly challenging also makes it doubly rewarding. The progress that CITAC has made over the years only adds to my optimism, and I wish to take this opportunity to remind you of how far we have come and how much further we hope to go.

The Need for an Executive Leadership Curriculum in Scientist-Clinician Training Programs.

The health of Canadians depends on effective leadership among health care providers to facilitate the translation of new health discoveries into clinical practice. Clinician-scientists play an important role in bridging the gap between research and clinical practice, and require effective leadership skills to advance clinical practice successfully. To accelerate the leadership development in clinician scientist trainees, with the aim of developing strong leaders in administration and health advocacy, the Leaders in Medicine (LIM) training program at the University of Calgary created an Executive Leadership Coaching Program involving three phases: 1) an evidence-based evaluation tool, the Core Values IndexTM (CVI), that was used to identify the key drivers behind how individuals can be most effective in making their contribution; 2) small group workshops to debrief the results of the CVI assessment; and 3) one-on-one executive coaching sessions to facilitate the discovery, development and deployment of individual leadership capabilities. Coaching in leadership strategies enables clinician-scientist trainees to lead, influence, manage and deliver science-based improvements into the practice of medicine. We strongly recommend that other Canadian scientist-clinician training programs consider opportunities like the ones we offer to our LIM trainees. This training has important implications for the delivery of healthcare in Canada.

Scientific overview on CSCI-CITAC Annual General Meeting and 2017 Young Investigators' Forum.

The 2017 Annual General Meeting of the Canadian Society of Clinician Investigators (CSCI) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was a national Annual General Meeting (AGM) held in Toronto, Ontario November 20-22, 2017, in conjunction with the University of Toronto Clinician Investigator Program Research Day. The theme for this year's meeting was "Roll up your sleeves-How to manage your physician scientist career", emphasizing lectures and workshops that were designed to provide tools for being proactive and successful in career planning. The keynote speakers were Dr. Rod McInnes (McGill University and Canadian Institutes of Health Research Acting President), who was the Distinguished Scientist Award recipient, Dr. David Goltzman (McGill University), who was the 2017 Henry Friesen Award recipient, Dr. Gillian Hawker (University of Toronto), Dr. Mike Sapieha (Université de Montréal), who was the 2017 Joe Doupe Award recipient, and Dr. Alex MacKenzie (Children's Hospital of Eastern Ontario Research Institute, University of Ottawa). The workshops, focusing on career development for clinician scientists, were hosted by Dr. Lisa Robinson, Dr. Nicola Jones, Kevin Vuong, Fran Brunelle, Dr. Jason Berman and Dr. Alan Underhill. Further to this, the Young Investigators' Forum encompasses presentations from scientist-clinician trainees from across the country. All scientific abstracts are summarized in this review. There were over 100 abstracts showcased at this year's meeting during the highlighted poster sessions, with six outstanding abstracts selected for oral presentations during the President's Forum.

Posttraumatic Osteoarthritis Development and Progression in an Ovine Model of Partial Anterior Cruciate Ligament Transection and Effect of Repeated Intra-articular Methylprednisolone Acetate Injections on Early Disease.

BACKGROUND: Partial anterior cruciate ligament (p-ACL) ruptures are a common injury of athletes. However, few preclinical models have investigated the natural history and treatment of p-ACL injuries. PURPOSE: To (1) demonstrate whether a controlled p-ACL injury model (anteromedial band transection) develops progressive gross morphological and histological posttraumatic osteoarthritis (PTOA)-like changes at 20 and 40 weeks after the injury and (2) investigate the efficacy of repeated (0, 5, 10, and 15 weeks) intra-articular injections of methylprednisolone acetate (MPA; 80 mg/mL) in the mitigation of potential PTOA-like changes after p-ACL transection. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-one 3- to 5-year-old female Suffolk-cross sheep were allocated to 4 groups: (1) nonoperative controls (n = 5), (2) 20 weeks after p-ACL transection (n = 5), (3) 40 weeks after p-ACL transection (n = 6), and (4) 20 weeks after p-ACL transection + MPA (n = 5). Gross morphological grading and histological analyses were conducted. mRNA expression levels for inflammatory, degradative, and structural molecules were assessed. RESULTS: p-ACL transection led to significantly more combined gross damage ( P = .008) and significant aggregate histological damage ( P = .009) at 40 weeks after p-ACL transection than the nonoperative controls, and damage was progressive over time. Macroscopically, MPA appeared to slightly mitigate gross damage at 20 weeks after p-ACL transection in some animals. However, microscopic analysis revealed that repeated MPA injections after p-ACL transection led to significant loss in proteoglycan content compared with the nonoperative controls and 20 weeks after p-ACL transection ( P = .008 and P = .008, respectively). CONCLUSION: p-ACL transection led to significant gross and histological damage by 40 weeks, which was progressive over time. Multiple repeated MPA injections were not appropriate to mitigate injury-related damage in a p-ACL transection ovine model as significant proteoglycan loss was observed in MPA-treated knees. CLINICAL RELEVANCE: A p-ACL injury leads to slow and progressive PTOA-like joint damage, and multiple repeated injections of glucocorticoids may be detrimental to the knee joint in the long term.

Scientific Overview on CSCI-CITAC Annual General Meeting and 2016 Young Investigators' Forum.

The 2016 Annual General Meeting of the Canadian Society of Clinician Investigators (CSCI) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was a national conference held in Toronto November 21-23, 2016, in conjunction with The University of Toronto Clinician Investigator Program Research Day. The theme for this year's meeting was "Mapping Your Career as a Clinician-Scientist"; emphasizing essential skills for developing a fruitful career as clinician-scientist. The meeting featured an opening presentation by Dr. Alan Underhill, Dr. Nicola Jones and Alexandra Kuzyk. The keynote speakers were Dr. Nada Jabado (McGill University), who discussed the association between cancer and histones, Dr. Norman Rosenblum (University of Toronto), who addressed the career path and the "calling" of the Clinician Scientist, Dr. Martin Schmeing (McGill University), who was the 2016 Joe Doupe Award recipient, and Dr. Linda Rabeneck (Cancer Care Ontario and University of Toronto), who received the Friends of CIHR lectureship. The workshops, focusing on career development for clinician scientists, were hosted by Drs. Alan Underhill, Nicola Jones, Lynn Raymond, Michael Schlossmacher and Norman Rosenblum, as well as University of Toronto communication specialists, Caitlin Johannesson and Suzanne Gold. In addition, the Young Investigators' Forum included presentations from clinician investigator trainees from across the country. The research topics were diverse and comprehensive: from basic sciences to clinical practice; from epidemiology to medical engineering. All scientific abstracts are summarized in this review. Over 70 abstracts were showcased at this year's meeting during two poster sessions, with six outstanding abstracts selected for oral presentations during the President's Forum.

Use of pre-clinical surgically induced models to understand biomechanical and biological consequences of PTOA development.

Post-traumatic osteoarthritis (PTOA) development is often observed following traumatic knee injuries involving key stabilising structures such as the cruciate ligaments or the menisci. Both biomechanical and biological alterations that follow knee injuries have been implicated in PTOA development, although it has not been possible to differentiate clearly between the two causal factors. This review critically examines the outcomes from pre-clinical lapine and ovine injury models arising in the authors' laboratories and differing in severity of PTOA development and progression. Specifically, we focus on how varying severity of knee injuries influence the subsequent alterations in kinematics, kinetics, and biological outcomes. The immediate impact of injury on the lubrication capacity of the joint is examined in the context of its influence on biomechanical alterations, thus linking the biological changes to abnormal kinematics, leading to a focus on the potential areas for interventions to inhibit or prevent development of the disease. We believe that PTOA results from altered cartilage surface interactions where biological and biomechanical factors intersect, and mitigating acute joint inflammation may be critical to prolonging PTOA development. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:454-465, 2017.

Location and gene-specific effects of methylprednisolone acetate on mitigating IL1ß-induced inflammation in mature ovine explant knee tissue.

OBJECTIVE AND DESIGN: To determine the ability of methylprednisolone acetate (MPA) to influence interleukin 1ß (IL1ß)-induced gene expression in ovine knee joint tissues. MATERIAL OR SUBJECTS: Ovine articular cartilage, synovium, and infrapatellar fat pad (IPFP) explants. TREATMENT: Explants were treated with 10-3 M or 10-4 M MPA. METHODS: Explant treatment groups: (1) control (DMEM); (2) inflammation (IL1ß); (3) IL1ß + 10-3 M MPA; or (4) IL1ß + 10-4 M MPA. Cell viability was assessed pre- and post-treatment. Expression of mRNA levels for inflammatory, degradative, anabolic, innate immunity, and adipose-related molecules was quantified via qPCR, and analyzed via the comparative C T method. RESULTS: Except for IL8 in a subset of cartilage locations, matrix metalloproteinases (MMPs) were the only genes consistently affected by MPA. MPA mitigated IL1ß-induced MMP3 expression levels in all regions of the articular cartilage, and in the synovium and IPFP, while MMP1 mRNA expression levels were significantly decreased with MPA after IL1ß in the tibial plateau and synovium, but paradoxical increases in the IPFP. MMP13 mRNA expression levels exhibited significant decreases with MPA after IL1ß in the femoral condyles, tibial plateau, synovium, and IPFP. CONCLUSIONS: MPA treatment suppressed IL1ß-induced mRNA levels for MMPs in articular cartilage, synovium, and IPFP and was found to be tissue-, location-, and gene-specific.

Single intra-articular dexamethasone injection immediately post-surgery in a rabbit model mitigates early inflammatory responses and post-traumatic osteoarthritis-like alterations.

Despite surgical reconstruction of the anterior cruciate ligament, a significant number of patients will still develop post-traumatic osteoarthritis (PTOA). Our objective was to determine if mitigating aspects of the acute phase of inflammation following a defined knee surgery with a single administration of a glucocorticoid could prevent the development of PTOA-like changes within an established rabbit model of surgically induced PTOA. An early and late post-surgical time-point was investigated in this study (48 h and 9 weeks post-surgery) in which the following groups were repeated (each n=6, for a total of 24 rabbits per time-point, and 48 rabbits used in the study): control (age/sex matched), sham (arthrotomy), drill injury (arthrotomy+two drill holes to a non-cartilaginous area of the femoral notch), and drill injury+single intra-articular (IA) injection of dexamethasone (DEX). At 48 h post-surgery, DEX treatment significantly lowered the mRNA levels for a subset of pro-inflammatory mediators, and significantly lowered the histological grade. Nine weeks post surgery, DEX treatment significantly lowered the histological scores (presented as effect size) for synovium (3.8), lateral femoral condyle (3.9), and lateral tibial cartilage (5.1) samples. Thus, DEX likely acts to prevent injury induced inflammation that could contribute to subsequent joint damage.

Characterization of proteoglycan 4 and hyaluronan composition and lubrication function of ovine synovial fluid following knee surgery.

The objective of this study was to determine changes in (1) proteoglycan 4 (PRG4) and hyaluronan (HA) concentration, (2) HA molecular weight (MW) distribution, and (3) cartilage boundary lubricating ability of synovial fluid (SF) from surgical sham (SHAM), anterior cruciate ligament (ACL)/medial collateral ligament (MCL) transection, and lateral meniscectomy (MEN) in a post-knee surgery ovine model. Ovine SF (oSF) was collected at euthanization 20 weeks after surgery, with the contralateral joint serving as the non-operative control. PRG4 and HA concentration in oSF was measured by sandwich enzyme-linked immunosorbent assay, and HA MW distribution by agarose gel electrophoresis. Cartilage boundary lubricating ability of oSF was measured by a cartilage-cartilage friction test. PRG4 and HA concentration in SHAM, ACL/MCL, and MEN oSF were similar in comparison to the contralateral control (CTRL) oSF. The HA MW distribution in the operated oSF for all ranges were similar to the respective CTRL oSF. The kinetic coefficients of friction in operated and CTRL oSF were similar in all groups, and were significantly lower than saline. These results indicate oSF lubricant composition and function at 20 weeks post-knee surgery were similar to contralateral CTRL, and suggest earlier time points post surgery warrant further investigation.