Proteomic analysis of synovial fluid identifies periostin as a biomarker for anterior cruciate ligament injury.

OBJECTIVE: Emerging evidence suggests that injury to the anterior cruciate ligament (ACL) typically initiates biological changes that contribute to the development of osteoarthritis (OA). The molecular biomarkers or mediators of these biological events remain unknown. The goal of this exploratory study was to identify novel synovial fluid biomarkers associated with early biological changes following ACL injury distinct from findings in end-stage OA. METHODS: Synovial fluid was aspirated from patients with acute (≤30 days) and subacute (31-90 days) ACL tears and from patients with advanced OA and probed via tandem mass spectrometry for biomarkers to distinguish OA from ACL injury. Periostin (POSTN) was identified as a potential candidate. Further analyses of POSTN were performed in synovial fluid, OA cartilage, torn ACL remnants, and cultured cells and media by Western blot, PCR, immunostaining and ELISA. RESULTS: Synovial fluid analysis revealed that POSTN exhibited higher expression in subacute ACL injury than OA. POSTN expression was relatively low in cartilage/chondrocytes suggesting it is also produced by other intra-articular tissues. Conversely, high and time-dependent expression of POSTN in ACL tear remnants and isolated cells was consistent with the synovial fluid results. CONCLUSIONS: Elevated POSTN may provide a synovial fluid biomarker of subacute ACL injury setting separate from OA. Increased expression of POSTN in ACL suggests that the injured ACL may play a pivotal role in POSTN production, which is sensitive to time from injury. Previous studies have shown potential catabolic effects of POSTN, raising the possibility that POSTN contributes to the initiation of joint degeneration and may offer a window of opportunity to intervene in the early stages of post-traumatic OA.

The cost of implanting a cemented versus cementless total knee arthroplasty.

AIMS: The aim of this study was to compare the actual cost of a cemented and cementless total knee arthroplasty (TKA) procedure. MATERIALS AND METHODS: The cost of operative time, implants, cement, and cementing accessories were included in the overall cost of the TKA procedure. Operative time was determined from a previously published study comparing cemented and cementless implants of the same design. The cost of operative time, implants, cement, and cementing accessories was determined from market and institutional data. RESULTS: Mean operative time for cemented TKA was 11.6 minutes longer for cemented TKA than cementless TKA (93.7 minutes (sd 16.7) vs 82.1 minutes (sd 16.6); p = 0.001). Using a conservative published standard of $36 per minute for operating theatre time cost, the total time cost was $418 higher for cementing TKA. The cost of cement and accessories ranged from $170 to $625. Overall, the calculated cost of cemented TKA is $588 to $1043, depending on technique. The general increased charge for cementless TKA implants over cemented TKA implants was $366. CONCLUSION: The overall procedural cost of implanting a cementless TKA is less than implanting a cemented TKA. Cost alone should not be a barrier to using cementless TKA. Cite this article: Bone Joint J 2019;101-B(7 Supple C):61-63.

Does patient-reported perception of pain differ based on surgical approach in total hip arthroplasty?

AIMS: Whether patient-reported pain differs among surgical approaches in total hip arthroplasty (THA) remains unclear. This study's purposes were to determine differences in pain based on surgical approach (direct anterior (DA) vs posterolateral (PL)) and PL approach incision length. PATIENTS AND METHODS: This was a retrospective investigation from two centres and seven surgeons (three DA, three PL, one both) of primary THAs. PL patients were categorized for incision length (6 cm to 8 cm, 8 cm to 12 cm, 12 cm to 15 cm). All patients had cementless femoral and acetabular fixation, at least one year's follow-up, and well-fixed components. Patients completed a pain-drawing questionnaire identifying the location and intensity of pain on an anatomical diagram. Power analysis indicated 800 patients in each cohort for adequate power to detect a 4% difference in pain (alpha = 0.05, beta = 0.80). RESULTS: A total of 1848 patients (982 DA, 866 PL) were included. PL patients were younger (59.4 years, sd 12.9 vs 62.7 years, sd 9.7; p < 0.001) and had shorter follow-up (3.3 years, sd 1.3 vs 3.7 years, sd 1.3; p < 0.001). DA patients reported decreased moderate to severe trochanteric (14% vs 21%; p < 0.001) and groin pain (19% vs 24%; p = 0.004) than PL patients. There were no differences in anterior, lateral, or posterior thigh, back, or buttock pain between cohorts (p = 0.05 to 0.7). PL approach incision length did not impact the incidence or severity of pain (p = 0.3 to 0.7). CONCLUSION: A significant proportion of patients perceive persistent pain following THA regardless of approach. DA patients reported less trochanteric and groin pain versus PL patients. PL incision length did not influence the incidence or severity of patient-reported pain. Cite this article: Bone Joint J 2019;101-B(6 Supple B):31-36.

Is a modular dual mobility acetabulum a viable option for the young, active total hip arthroplasty patient?

AIMS: Modular dual mobility (DM) prostheses in which a cobalt-chromium liner is inserted into a titanium acetabular shell ( vs a monoblock acetabular component) have the advantage of allowing supplementary screw fixation, but the potential for corrosion between the liner and acetabulum has raised concerns. While DM prostheses have shown improved stability in patients deemed 'high-risk' for dislocation undergoing total hip arthroplasty (THA), their performance in young, active patients has not been reported. This study's purpose was to assess clinical outcomes, metal ion levels, and periprosthetic femoral bone mineral density (BMD) in young, active patients receiving a modular DM acetabulum and recently introduced titanium, proximally coated, tapered femoral stem design. PATIENTS AND METHODS: This was a prospective study of patients between 18 and 65 years of age, with a body mass index (BMI) < 35 kg/m2 and University of California at Los Angeles (UCLA) activity score > 6, who received a modular cobalt-chromium acetabular liner, highly crosslinked polyethylene mobile bearing, and cementless titanium femoral stem for their primary THA. Patients with a history of renal disease and metal hardware elsewhere in the body were excluded. A total of 43 patients (30 male, 13 female; mean age 52.6 years (sd 6.5)) were enrolled. All patients had a minimum of two years' clinical follow-up. Patient-reported outcome measures, whole blood metal ion levels (ug/l), and periprosthetic femoral BMD were measured at baseline, as well as at one and two years postoperatively. Power analysis indicated 40 patients necessary to demonstrate a five-fold increase in cobalt levels from baseline (alpha = 0.05, beta = 0.80). A mixed model with repeated measures was used for statistical analysis. RESULTS: Mean Harris Hip Scores improved from 54.1 (sd 20.5) to 91.2 (sd 10.8) at two years postoperatively (p < 0.001). All patients had radiologically well-fixed components, no patients experienced any instability, and no patients required any further intervention. Mean cobalt levels increased from 0.065 ug/l (sd 0.03) preoperatively to 0.30 ug/l (sd 0.51) at one year postoperatively (p = 0.01) but decreased at two years postoperatively to 0.16 ug/l (sd 0.23; p = 0.2). Four patients (9.3%) had a cobalt level outside the reference range (0.03 ug/l to 0.29 ug/l) at two years postoperatively, with values from 0.32 ug/l to 0.94 ug/l. The mean femoral BMD ratio was maintained in Gruen zones 2 to 7 at both one and two years postoperatively using this stem design. At two years postoperatively, mean BMD in the medial calcar was 101.5% of the baseline value. CONCLUSION: Use of a modular DM prosthesis and cementless, tapered femoral stem has shown encouraging results in young, active patients undergoing primary THA. Elevation in mean cobalt levels and the presence of four patients outside the reference range at two years postoperatively demonstrates the necessity of continued surveillance in this cohort. Cite this article: Bone Joint J 2019;101-B:365-371.

Molecular influence of anterior cruciate ligament tear remnants on chondrocytes: a biologic connection between injury and osteoarthritis.

OBJECTIVE: Anterior cruciate ligament (ACL) injury initiates a cascade of events often leading to osteoarthritis (OA). ACL reconstruction does not alter the course of OA, suggesting that heightened OA risk is likely due to factors in addition to the joint instability. We showed that torn ACL remnants express periostin (POSTN) in the acute phase of injury. Considering that ACL injury predisposes to OA and that POSTN is associated with cartilage metabolism, we hypothesize that ACL injury affects chondrocytes via POSTN. DESIGN: Cartilage was obtained from osteoarthritic patients and ACL remnants were collected from patients undergoing ACL reconstruction. Crosstalk between ACL remnants and chondrocytes was studied in a transwell co-culture system. Expression of POSTN and other anabolic and catabolic genes was assessed via real-time polymerase chain reaction (PCR). Immunostaining for periostin was performed in human and mouse cartilage. The impact of exogenous periostin and siRNA-mediated ablation of periostin on matrix metabolism and cell migration was examined. Furthermore, the effect of anabolic (transforming growth factor beta 1 [TGF-ß1]) and catabolic (interleukin 1 beta [IL-1ß]) factors on POSTN expression was investigated. RESULTS: ACL remnants induced expression of POSTN, MMP13 and ADAMTS4. Periostin levels were significantly higher in osteoarthritic compared to normal cartilage. Exogenous periostin induced MMP13 expression and cell migration, and repressed COL1A1 expression while POSTN knockdown inhibited expression of both anabolic and catabolic genes and impeded cell migration. TGF-ß1 and IL-1ß treatment did not alter POSTN expression but influenced chondrocyte metabolism as determined by quantification of anabolic and catabolic genes via real-time PCR. CONCLUSIONS: ACL remnants can exert paracrine effects on cartilage, altering cellular homeostasis. Over time, this metabolic imbalance could contribute to OA development.

Tranexamic acid: optimal blood loss management in surface replacement arthroplasty.

AIMS: This study investigated whether the use of tranexamic acid (TXA) decreased blood loss and transfusion related cost following surface replacement arthroplasty (SRA). METHODS: A retrospective review of patients treated with TXA during a SRA, who did not receive autologous blood (TXA group) was performed. Two comparison groups were established; the first group comprised of patients who donated their own blood pre-operatively (auto group) and the second of patients who did not donate blood pre-operatively (control). Outcomes included transfusions, post-operative haemoglobin (Hgb), complications, and length of post-operative stay. RESULTS: Between 2009 and 2013, 150 patients undergoing SRA were identified for inclusion: 51 in the auto, 49 in the control, and 50 in the TXA group. There were no differences in the pre-operative Hgb concentrations between groups. The mean post-operative Hgb was 11.3 g/dL (9.1 to 13.6) in the auto and TXA groups, and 10.6 g/dL (8.1 to 12.1)in the control group (p = 0.001). Accounting for cost of transfusions, administration of TXA, and length of stay, the cost per patient was $1731, $339, and $185 for the auto, control and TXA groups, respectively. DISCUSSION: TXA use demonstrated higher post-operative Hgb concentrations when compared with controls and decreased peri-operative costs. TAKE HOME MESSAGE: Tranexamic acid safely limits allogeneic transfusion, maintains post-operative haemoglobin, and decreases direct and indirect transfusion related costs in surface replacement arthroplasty.

Increased risk of failure following revision total knee replacement in patients aged 55 years and younger.

The aims of this retrospective study were to compare the mid-term outcomes following revision total knee replacement (TKR) in 76 patients (81 knees) < 55 years of age with those of a matched group of primary TKRs based on age, BMI, gender and comorbid conditions. We report the activity levels, functional scores, rates of revision and complications. Compared with patients undergoing primary TKR, those undergoing revision TKR had less improvement in the mean Knee Society function scores (8.14 (-55 to +60) vs 23.3 points (-40 to +80), p < 0.001), a similar improvement in UCLA activity level (p = 0.52), and similar minor complication rates (16% vs 13%, p = 0.83) at a mean follow-up of 4.6 years (2 to 13.4). Further revision surgery was more common among revised TKRs (17% vs 5%, p = 0.02), with deep infection and instability being the most common reasons for failure. As many as one-third of patients aged < 55 years in the revision group had a complication or failure requiring further surgery. Young patients undergoing revision TKR should be counselled that they can expect somewhat less improvement and a higher risk of complications than occur after primary TKR.

Patient dissatisfaction following total knee replacement: a growing concern?

A national, multi-centre study was designed in which a questionnaire quantifying the degree of patient satisfaction and residual symptoms in patients following total knee replacement (TKR) was administered by an independent, blinded third party survey centre. A total of 90% of patients reported satisfaction with the overall functioning of their knee, but 66% felt their knee to be 'normal', with the reported incidence of residual symptoms and functional problems ranging from 33% to 54%. Female patients and patients from low-income households had increased odds of reporting dissatisfaction. Neither the use of contemporary implant designs (gender-specific, high-flex, rotating platform) or custom cutting guides (CCG) with a neutral mechanical axis target improved patient-perceived outcomes. However, use of a CCG to perform a so-called kinematically aligned TKR showed a trend towards more patients reporting their knee to feel 'normal' when compared with a so called mechanically aligned TKR This data shows a degree of dissatisfaction and residual symptoms following TKR, and that several recent modifications in implant design and surgical technique have not improved the current situation.

Clinical outcomes following re-admission for non-infectious wound complications after primary total knee replacement.

Haematomas, drainage, and other non-infectious wound complications following total knee replacement (TKR) have been associated with long-term sequelae, in particular, deep infection. However, the impact of these wound complications on clinical outcome is unknown. This study compares results in 15 patients re-admitted for wound complications within 90 days of TKR to 30 matched patients who underwent uncomplicated total knee replacements. Patients with wound complications had a mean age of 66 years (49 to 83) and mean body mass index (BMI) of 37 (21 to 54), both similar to that of patients without complications (mean age 65 years and mean BMI 35). Those with complications had lower mean Knee Society function scores (46 (0 to 100 vs. 66 (20 to 100), p = 0.047) and a higher incidence of mild or greater pain (73% vs. 33%, p = 0.01) after two years compared with the non re-admitted group. Expectations in patients with wound complications following TKR should be tempered, even in those who do not develop an infection.

Differentiation of human bone marrow mesenchymal stem cells on decellularized extracellular matrix materials.

Mesenchymal bone marrow stromal cells may be a source of cells to preseed decellularized biologic mesh materials for improved cellularization and promote a more physiologic tissue after remodeling. Spontaneous differentiation of mesenchymal stromal cells on the decellularized material would be undesirable. Conversely, induced differentiation of mesenchymal stem cells (MSC) on the material would suggest that these materials may have promise as scaffold materials for bone, cartilage, or adipocyte formation. Two sources of mesenchymal cells were evaluated for induced differentiation in control wells. These MSCs were also evaluated for spontaneous or induced differentiation on decellularized porcine dermis and mesothelium materials. Primarily harvested bone marrow MSCs and commercially obtained MSCs were induced into osteoblasts and adipocytes on decellularized dermis and mesothelium materials. The MSCs were able to be induced into chondrocytes in pellet form but not when grown as a monolayer on the materials. The MSCs did not undergo spontaneous differentiation when grown on the materials for up to four weeks. MSC grown on decellularized porcine dermis or mesothelium do not spontaneously differentiate and may serve as a source of autologous cells for preseeding these extracellular matrix materials prior to implantation.

Patient specific cutting blocks are currently of no proven value.

Patient specific cutting guides generated by preoperative Magnetic Resonance Imaging (MRI) of the patient's extremity have been proposed as a method of improving the consistency of Total Knee Arthroplasty (TKA) alignment and adding efficiency to the operative procedure. The cost of this option was evaluated by quantifying the savings from decreased operative time and instrument processing costs compared to the additional cost of the MRI and the guide. Coronal plane alignment was measured in an unselected consecutive series of 200 TKAs, 100 with standard instrumentation and 100 with custom cutting guides. While the cutting guides had significantly lower total operative time and instrument processing time, the estimated $322 savings was overwhelmed by the $1,500 additional cost of the MRI and the cutting guide. All measures of coronal plane alignment were equivalent between the two groups. The data does not currently support the proposition that patient specific guides add value to TKA.

Genetics informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT): rationale and study design.

The risk of venous thromboembolism (VTE) is higher after the total hip or knee replacement surgery than after almost any other surgical procedure; warfarin sodium is commonly prescribed to reduce this peri-operative risk. Warfarin has a narrow therapeutic window with high inter-individual dose variability and can cause hemorrhage. The genetics-informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT) is a 2 × 2 factorial-design, randomized controlled trial designed to compare the safety and effectiveness of warfarin-dosing strategies. GIFT will answer two questions: (1) does pharmacogenetic (PGx) dosing reduce the rate of adverse events in orthopedic patients; and (2) is a lower target international normalized ratio (INR) non-inferior to a higher target INR in orthopedic participants? The composite primary endpoint of the trial is symptomatic and asymptomatic VTE (identified on screening ultrasonography), major hemorrhage, INR ≥ 4, and death.