The aim of this study was to determine the incidence, annual trend, perioperative outcomes, and identify risk factors of early-onset (≤ 90 days) deep surgical site infection (SSI) following primary total knee arthroplasty (TKA) for osteoarthritis. Risk factors for early-onset deep SSI were assessed. We performed a retrospective population-based cohort study using prospectively collected patient-level data from several provincial administrative data repositories between January 2013, and March 2020. The diagnosis of early-onset deep SSI was based on published Centre for Disease Control/National Healthcare Safety Network (CDC/NHSN) definitions. The Mann-Kendall Trend Test was used to detect monotonic trends in early-onset deep SSI rates over time. The effects of various patient and surgical risk factors for early-onset deep SSI were analyzed using multiple logistic regression. Secondary outcomes were 90-day mortality and 90-day readmission. A total of 20,580 patients underwent primary TKA for osteoarthritis. Forty patients had a confirmed deep SSI within 90-days of surgery representing a cumulative incidence of 0.19%. The annual infection rate did not change over the 7-year study period (p = 0.879). Risk factors associated with early-onset deep SSI included blood transfusions (OR, 3.93 [95% CI 1.34-9.20]; p=0.004), drug or alcohol abuse (OR, 4.91 [95% CI 1.85-10.93]; p<0.001), and surgeon volume less than 30 TKA per year (OR, 4.45 [1.07-12.43]; p=0.013). Early-onset deep SSI was not associated with 90-days mortality (OR, 11.68 [0.09-90-58]; p=0.217), but was associated with an increased chance of 90-day readmission (OR, 50.78 [26.47-102.02]; p<0.001). This study establishes a reliable baseline infection rate for early-onset deep SSI after TKA for osteoarthritis through the use of a robust methodological process. Several risk factors for early-onset deep SSI are potentially modifiable or can be optimized prior to surgery and be effective in reducing the incidence of early-onset SSI. This could guide the formulation of provincial screening programs and identify patients at high risk for SSI.
There has been growing interest in the literature regarding evaluation of functional outcomes in patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA) while suffering from depression and using selective serotonin reuptake inhibitors (SSRI). Previous literature has shown that these patients have lower post-operative functional scores compared to those without SSRI use and with multiple musculoskeletal co-morbidities. This might be the result of potentially suboptimal motivation and participation in the post-operative rehabilitation programs. One recent study from a single center has suggested a reduction in adverse events in patients undergoing arthroplasty while on SSRI. The purpose of this study is to evaluate the post operative functional scores of patients on SSRI and compare them with the patients not prescribed SSRIs. A retrospective data analysis was performed on patients who had primary TKA and primary THA between 1st June 2014 and 31st May 2017. The patients into two groups. In the first, patients received SSRI for at least one year before the surgery while in group two, patients did not receive SSRI. Outcome measures included Western Ontario and McMaster university osteoarthritis index (WOMAC) and EQ5D5L scores at pre surgery, three months and 12 months post surgery. Chi-square and t test was used to compare categorical variables and continuous variables respectively. Multivariate linear regression was conducted to compare the change of scores between the two groups and was adjusted for age, gender, and comorbidities. These outcome scores were analyzed separately for TKA and THA. In the TKA group, there were 1,452 patients using SSRI and 15,981 not using SSR. In the THA group there were 851 patients using SSRIs and 10,102 patients without SSRIs. The baseline WOMAC for TKA patients was 45.6 for the controls and 41.8 for those patients on SSRIs (p < 0 .001). The baseline EQ5DL was 0.53 and 0.46 in the same groups (p < 0 .001). The baseline WOMAC for THA patients was 39.1 for the controls and 36.2 for patients using SSRIs (p < 0 .001). The baseline EQ5DL scores were 0.43 and 0.37respectively, again indicating patients on SSRI therapy had lower baseline scores (p < 0 .001). There was improvement in WOMAC and EQ5DL scores in all patient groups at 3 months and 12 months. After adjusting for gender, age, comorbidities and baseline score, THA patients not using SSRI showed a greater improvement in their WOMAC and EQ5DL scores than those prescribed SSRIs, WOMAC (p=0.008), EQ5DL (p=0.001). TKA patients showed a similar outcome but only the EQ5DL was statistically significant, WOMAC (p=0.12), EQ5DL (p=0.036). Our results show that patients on SSRI have lower preoperative WOMAC and EQ5DL scores at baseline when compared to patients not undergoing treatment for depression or anxiety with SSRIs. After arthroplasty, patients using SSRIs show significant improvement at 12 months but the improvement is smaller than the group not using SSRIs.
Osteoarthritis (OA) is the fastest growing global health problem, with a total joint replacement being the only effective treatment for patients with end stage OA. Many groups are examining the use of bone marrow or adipose derived mesenchymal stem cells (MSCs) to repair cartilage, or modulate inflammation to promote healing, however, little efficacy in promoting cartilage repair, or reducing patient symptoms over temporary treatments such as micro-fracture has been observed. There is a growing body of literature demonstrating that MSCs derived from the synovial lining of the joint are superior in terms of chondrogenic differentiation and while improvements in clinical outcome measures have been observed with synovial MSCs, results from clinical studies are still highly variable. Based on our results, we believe this variability in clinical studies with MSCs results in part from the isolation, expansion and re-injection of distinct MSCs subtypes in normal vs. OA tissues, each with differing regenerating potential. However, it remains unknown if this heterogeneity is natural (e.g. multiple MSC subtypes present) or if MSCs are influenced by factors in vivo (disease state/stage). Therefore, in this study, we undertook an ‘omics’ screening approach on MSCs from normal and OA knee synovial tissue. Specifically, we characterized their global proteome and genomic expression patterns to determine if multiple MSC from normal and OA joints are distinct at the protein/gene expression level and/if so, what proteins/genes are differentially expressed between MSCs derived from normal and OA synovial tissue. Synovium tissue was collected from OA patients undergoing joint replacement and normal cadaveric knees. The in vitro adipogenic, chondrogenic and osteogenic differentiation potential of the MSCs was analyzed via qPCR and histology. Fully characterized MSC populations where then analyzed through an unbiased shotgun proteomics, and microarray analysis. Synovial MSCs isolated from both OA and normal knees demonstrated similar multipotent differentiation capacity. Likewise, both OA and normal MSCs display the typical MSCs cell surface marker profile in vitro (CD90+, CD44+, CD73+, CD105+). Using shotgun proteomics, 7720 unique peptides corresponding to 2183 proteins were identified and quantified between normal and OA MSCs. Of these 2183 proteins, 994 were equally expressed in normal and OA, MSCs, 324 were upregulated in OA MSCs (with 50 proteins exclusively expressed in OA MSCs), 630 proteins were upregulated in normal MSCs (with 16 proteins exclusively expressed in normal MSCs). Microarray analysis of normal and OA MSCs demonstrated a similar result in where, 967 genes were differentially expressed between normal and OA MSCs, with 423 genes upregulated in OA, and 544 genes upregulated in normal MSCs. In this project, we have demonstrated that although normal and OA synovial derived MSCs demonstrate similar multipotent differentiation potential and cell surface markers expression, these cells demonstrated significant differences at the molecular level (protein and gene expression). Further research is required to determine if these differences influence functional differences in vitro and/or in vivo and what drives this dramatic change in the regulatory pathways within normal vs. OA synovial MSCs.
Despite recent advances in the management of slipped capital femoral epiphysis (SCFE), controversy remains about the treatment of choice for unstable slips. Surgical dislocation and open reduction has the advantage of identifying and preserving the blood supply of femoral head thereby potentially reducing the risk of avascular necrosis, (AVN). There is large variation in the literature from several small series about reported AVN rates ranging from two to 66% for unstable SCFE treated with surgical dislocation. The aim of our study was to analyze our experience with acute open reduction and internal fixation of unstable acute and unstable acute on chronic slips using the technique of surgical dislocation described by Professor Reinhold Ganz. A retrospective review of 11 patients (12 hips) treated by surgical dislocation, reduction and pinning as the primary procedure for unstable acute and unstable acute on chronic SCFE in a tertiary referral children's hospital was undertaken. This represents the entire series treated in this manner from September 2007 to January 2018. These procedures were performed by a team of Orthopaedic surgeons with significant experience performing surgical dislocation of the hip including patients with chronic SCFE, Perthes' disease, impingement and acetabular fractures. Demographic data, intraoperative records, postoperative notes and radiographs including details of subsequent surgery were reviewed. There were seven boys and four girls with mean age of 13.4 years, range 11 to 15 years at the time of surgical dislocation. Out of 12 hips, two had acute unstable slip while the remaining 10 had acute on chronic unstable slip. Six patients had good or excellent results. The remaining six patients developed AVN of which three patients had total hip replacement at six months, 17 months and 18 months following primary procedure. Seven patients required more than one operation. Three patients lost their correction and required re fixation despite surgical dislocation, reduction and fixation being their primary procedure. This series demonstrates a high percentage of AVN (50%) in severe unstable SCFE treated with surgical dislocation despite careful attention to retinacular flap development and intra operative doppler studies. This is in direct contrast to our experience with subcapital reorientation with surgical dislocation in stable slips where excellent results were achieved with a low rate of AVN. Pre-operative imaging with MRI and perfusion studies may identify where ischemia has occurred and might influence operative treatment. Based on our results, we do not recommend routine use of surgical dislocation in unstable SCFE. This technique requires further scrutiny to define the operative indications in unstable SCFE.
There is currently no cure for osteoarthritis (OA), although there are ways to manage it, but most require quite invasive surgeries. There is a resident mesenchymal progenitor cell (MPC) population within the synovial membrane of the joint that have the ability to differentiate into bone, fat, and cartilage. We hypothesise that Method optimisation protocol: Synovial biopsies (2 or 5mm) were obtained from patients undergoing surgery. The biopsies were digested in either collagenase type I, IA, IV or II at a concentration of 0.5 or 1.0 mg/mL. Digestion was conducted at 37°C for 30, 60, 90 or 120min. To assay for the number of MPCs obtained, the cell suspension was stained with CD90 (a synovial MPC marker) and magnetically purified. The purified cells were then assayed by flow cytometry (Co-stained with a live/dead cell marker, BV510) or bright-field microscopy. Study protocol: Synovial tissues were digested in type IV collagenase for two hours to obtain a single cell suspension. The cells were subsequently stained with mesenchymal stem cell markers, including CD 90, CD 271, CD 44, CD73, and CD105, a macrophage marker, CD68. The macrophages were excluded and the remaining cells were index sorted into 96-well plates. The cells were expanded, and underwent 21-day chondrogenic, adipogenic, and osteogenic differentiation. Differentiation was assayed using RT-qPCR and histological methods. Additionally, the cells were re-analysed for marker expression after culturing. Optimisation: Synovial biopsies of 5mm produced a greater number of live CD90+ cells than 2mm biopsies. It was observed that type IV collagenase at 1mg/ML treatment for 120 min (hip) and 90 min (knee) obtained the greatest number of CD90+ MPCs from the synovium. Results: A single cell was isolated from an OA hip biopsy and was positive for the markers CD90, CD44, CD73, and negative for the markers CD68, CD271, CD105. Following differentiation, PCR analysis suggested that the cell line was able to differentiate into chondrocytes and adipocytes, but not osteoblasts. Histology data agreed with the PCR data with the adipocytes and chondrocytes having positive staining, whereas the osteoblasts were negative. FACS analysis following proliferation showed that the expression MPCs express cell surface markers that provide information as to populations have the best cartilage regeneration abilities. By determining the properties of the MPCs in OA hips that allow for better chondrogenic differentiation abilities
To identify the differences in inflammatory profiles between hip OA, knee OA and non-OA control cohorts and investigate the association between cytokine expression and clinical outcome measurements, specifically pain. A total of 250 individuals were recruited in three cohorts (100 knee OA, 50 hip OA, 100 control). Serum was collected and inflammatory profiles analysed using the Multiplex Human Cytokine Panel (Millipore) on the Luminex 100 platform (Luminex Corp., Austin, TX). The pain, physical function and activity limitations of hip OA cohort were scored using the WOMAC, SF-36, HHS and UCLA scores. All cytokine levels were compared between cohorts individually using Mann–Whitney–Wilcoxon (MWW) test with Bonferroni multiple comparison correction. Within hip OA cohorts, the effect of hip alignment (impingement and dysplasia) and radiographic grade (Kellgren and Lawrence grade, K/L grade) on cytokine levels were accessed by MWW test. Spearman's rank correlation test used to assess the association between cytokines and pain levels. The three cohorts showed distinct inflammatory profiles. Specifically, EGF, FGF-2, MCP-3, MIP-1a, IL-8 were significant different between knee and hip OA; FGF-2, GRO, IL-8, MCP-1, VEGF were significant different between hip OA and control; Eotaxin, GRO, MCP-1, MIP-1b, VEGF were significant different between knee OA and control (p-value < 0.0012). For hip OA cohorts, cytokines do not differ between K/L grade three and K/L grade four or between patients that displayed either impingement or dysplasia. Three cytokines were significant associated with pain: IL-6 (p-value = 0.045), MDC (p-value = 0.032) and IP-10 (p-value = 0.038). We have demonstrated that differences in serum inflammatory profiles exist between hip and knee OA patients. These differences suggest that OA may include different inflammatory subtypes according to affected joints. We also identified that the cytokine IL-6, MDC and IP-10 are associated with pain level in hip OA patients. These cytokines might help explain the inconsistent of presentation of pain with radiographical severity of OA joints. Future studies are needed to validate our findings and then to understand the following questions: (1) how differently affected joints are reflected in systematic biomarkers; (2) how these cytokines are biologically involved in the OA pain pathway.
Patients undergoing Joint Arthroplasty received a significant proportion of blood transfusions. In this study, we compared the risk of Deep Infection, and Superficial Infection post operation following Primary Total Hip or Knee replacement in blood-transfused and non-blood-transfused patients. Cohort of patients who underwent primary total Hip or Knee Arthroplasty from April 2012 to March 2015 in Alberta. Patient characteristics, comorbidity, received blood transfusion were collected from electronic medical records, operating room information systems, discharge abstract database, provincial clinical risk grouper data. Deep Infection and Superficial Infection were captured from Provincial Surgical Site Infection Surveillance data. Deep Infection include deep incisional and organ/space infections. Logistic regression analysis were used to compare Deep Infection and Superficial Infection in blood-transfused and non-blood-transfused cohorts, and risk-adjusted for age, gender, procedure type, and co-morbidities. Our study cohort contains 27891 patients, with mean of age at admission was 66.3±10.4, 57.5% female, 49.3% had 1 or more comorbidities. 58.8% underwent Knee Replacement. 11.1% received blood transfusion during hospital stay (Total Hip Replacement (THR) =13.1% and Total Knee Replacement (TKR) =9.7%,). 1.1% had Deep Infection (THR=1.4% and TKR=0.9%) and 0.5% had Superficial Infection (THR=0.5% and TKR=0.5%). Blood-transfused patients got 1.7% Deep Infection and 1.0% Superficial infection. Non-blood-transfused patients got 1.0% Deep Infection and 0.5% Superficial infection. Controlling for age, gender, procedure type, and co-morbidities, the odds of Deep Infection were 1.6 times higher for blood-transfused patients than for non-blood-transfused patients (adjusted odds ratio [OR]=1.6, 95% confidence interval [CI] [1.2–2.2], p=0.004). The odds of Superficial Infection were 2.0 times higher for transfused patients (adjusted OR=2.0, 95% CI [1.3–3.0], p=0.002). Blood transfusion increases Deep Infection and Superficial Infection post-surgery following Primary Total Knee or Hip Replacement. This finding suggests to reduce the unnecessary blood transfusion for patients considering Joint Arthroplasty. Reducing the blood transfusion will save the inpatient cost and decrease the infective complications post-surgery in Hip or Knee Arthroplasty patients.
In a cross sectional cohort study three different metal on metal total hip systems were assessed. Two monoblock acetabular designs; the Durom socket (Zimmer, Warsaw, In) and the Birmingham socket (Smith and Nephew, Memphis, TN), and one modular metal on metal total hip system (Pinnacle, Depuy Orthopaedics, Warsaw, In) in patients who have received these implants in the our region. 56 patients were recruited in total. All patients were assessed clinically, radiologically and biochemically. Whole blood Cobalt, Chromium and titanium levels were tested. The median head size used in the Birmingham group was 52mm (Range 44mm to 56mm), and in the Durom group, 48mm (Range 42 to 54mm). The median head size used in the modular Pinnacle group was 40mm (Range 36–44mm). The blood metal ions levels in the larger non modular acetabular sockets were significantly raised compared to the Pinnacle group. For Co 1.95 µg/l and 2.70 µg/l in the Durom and Birmingham groups respectively compared to only 0.52 µg/l in the Pinnacle group (P< 0.001). Mean Cr levels were the same for the two monoblock systems, 1.9 µg/l compared to the Pinnacle sockets 1.2 µg/l (P< 0.001). Our study clearly demonstrates that there is a significant difference in metal ion levels in patients following a monobloc large head arthroplasty system compared to a smaller modular metal on metal hip arthroplasty. The smaller head size appears to produce less metal ions whilst at the same time a 36mm–44mm head size is large enough to increase hip stability and range of movement as well as decreasing the risk of impingement. In our practice we are no longer using this design and the safest strategy, when considering metal on metal bearings, is to use a modular, smaller head system such as the Pinnacle.
To determine whether there is a difference in the metal ion levels among three different metal-on-metal total hip systems: two monoblock large heads and one modular metal-on-metal total hip replacement system in patients who received these implants in our region. A group of 56 patients were recruited that had either undergone total hip replacement (THR) with a Birmingham resurfacing socket, the Durom resurfacing socket, or a Pinnacle metal-on-metal bearing surface. All patients recruited were at least one year following their surgery in order that their ion levels had reached a steady state. We reviewed every patient clinically, radiographically as well as biochemically. Blood was obtained for cobalt (Co) and chromium (Cr) levels. Current radiographs were arranged to assess the stability and mechanics of the total hip systems. All patients signed an informed consent and completed three questionnaires, The Western Ontario and McMaster Universities (WOMAC) index, the Short Form 36 (SF36) and UCLA activity score. A Harris Hip score was completed in order to assess individual hip function. Statistical analysis was performed on the collected data to assess whether there were any other potential influence on the mean levels of Co and Cr.Purpose
Method
Elevated blood metal ions are associated with the early failure of the Hip Resurfacing Arthroplasty. The aim of this study was to analyse our prospective database of Hip Resurfacing Arthroplasty patients, to independently review the outliers with elevated blood metal ions and to determine whether a screening program would be of value at our institution. In 2004 a ten year prospective longitudinal study was set up to evaluate the clinical effectiveness and safety of Metal on Metal Hip Resurfacings in young, active adults with degenerative hip disease. Six hundred and four patients have enrolled in this multi-surgeon prospective study with strict inclusion criteria for Hip Resurfacing Arthroplasty. All have received the same implant design. All have completed validated functional outcome questionnaires at baseline, three and six months, then annually. A sub-cohort of 196 patients underwent whole blood chromium and cobalt analysis at the same time periods. Metal on metal bearings have a running in period of a minimum of six months before a steady state wear pattern is attained. We chose five parts per billion for Cobalt or Chromium as our threshold value. This value corresponds to the workplace exposure limit in the United Kingdom to Cobalt in whole blood. Therefore patients with ion levels greater than five parts per billion after six months were recalled for independent review, including further metal ion analysis.Purpose
Method