Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models.

Genetic absence of the urokinase-type plasminogen activator (uPA) reduces arthritis progression in the collagen-induced arthritis (CIA) mouse model to an extent just shy of disease abrogation, but this remarkable observation has not been translated into therapeutic intervention. Our aim was to test the potential in mice of an Ab that blocks the proteolytic capacity of uPA in the CIA model and the delayed-type hypersensitivity arthritis model. A second aim was to determine the cellular origins of uPA and the uPA receptor (uPAR) in joint tissue from patients with rheumatoid arthritis. A mAb that neutralizes mouse uPA significantly reduced arthritis progression in the CIA and delayed-type hypersensitivity arthritis models. In the CIA model, the impact of anti-uPA treatment was on par with the effect of blocking TNF-α by etanercept. A pharmacokinetics evaluation of the therapeutic Ab revealed target-mediated drug disposition consistent with a high turnover of endogenous uPA. The cellular expression patterns of uPA and uPAR were characterized by double immunofluorescence in the inflamed synovium from patients with rheumatoid arthritis and compared with synovium from healthy donors. The arthritic synovium showed expression of uPA and uPAR in neutrophils, macrophages, and a fraction of endothelial cells, whereas there was little or no expression in synovium from healthy donors. The data from animal models and human material provide preclinical proof-of-principle that validates uPA as a novel therapeutic target in rheumatic diseases.

Introduction of a New Treatment Algorithm Reduces the Number of Periprosthetic Femoral Fractures After Primary Total Hip Arthroplasty in Elderly Females.

BACKGROUND: Increasing global usage of cementless prostheses in total hip arthroplasty (THA) presents a challenge, especially for elderly patients. To reduce the risk of early periprosthetic femoral fractures (PFFs), a new treatment algorithm for females older than 60 years undergoing primary THA was introduced. The aim of this study was to determine the impact of the new treatment algorithm on the early risk of perioperative and postoperative PFFs and guideline compliance. METHODS: A total of 2405 consecutive THAs that underwent primary unilateral THA at our institution were retrospectively identified in the period January 1, 2013-December 31, 2018. A new treatment algorithm was introduced on April 1, 2017 with female patients aged older than 60 years intended to receive cemented femoral components. Before this, all patients were scheduled to receive cementless femoral components. Demographic data, number of perioperative and postoperative PFFs, and surgical compliance were recorded, analyzed, and intergroup differences compared. RESULTS: The utilization of cemented components in female patients older than 60 years increased from 12.3% (n = 102) to 82.5% (n = 264). In females older than 60 years, a significant reduction in the risk in early postoperative and intraoperative PFF after introduction of the new treatment algorithm was seen (4.57% vs 1.25%; P = .007 and 2.29% vs 0.31%; P = .02, respectively). Overall risk for postoperative and intraoperative fractures combined was also reduced in the entire cohort (4.1% vs 2.0%; P = .01). CONCLUSION: Use of cemented fixation of the femoral component in female patients older than 60 years significantly reduces the number of PFFs. Our findings support use of cemented femoral fixation in elderly female patients.

Cementless One-Stage Revision in Chronic Periprosthetic Hip Joint Infection. Ninety-One Percent Infection Free Survival in 56 Patients at Minimum 2-Year Follow-Up.

BACKGROUND: Cementless 1-stage revision in chronic periprosthetic hip joint infections is limited evaluated. The purpose of this study was to evaluate a specific treatment protocol in this patient group. METHODS: The study was performed as a multicenter, proof-of-concept, observational study with prospective data collection. Patients were treated with a cementless 1-stage revision according to the CORIHA protocol between 2009 and 2014. Fifty-six patients, McPherson type III-A/B-1/2, were enrolled with a mean follow-up time from the CORIHA procedure of 4 years (minimum of 2 years). The primary outcome was re-revision performed due to infection and was evaluated by competing risk analysis, with death and aseptic revision as competing events. All-cause mortality was evaluated by Kaplan-Meier survival analysis. Oxford Hip Score (OHS) was used as disease-specific patient-reported outcome measure. RESULTS: The cumulative incidence of re-revision due to infection was 8.9% (confidence interval [CI] 3.2%-18.1%). The 1-year and 5-year survival incidence was 96% (CI 86%-99%) and 89% (CI 75%-95%). OHS at baseline was 19.9 (CI 17.3-22.6) and at 24-month follow-up 35.1 (CI 31.7-38.5). The mean change in OHS from baseline to 24-month follow-up was 11.8 points (CI 7.3; 16.3). Three patients had aseptic revision performed: two suffered periprosthetic fractures and one had stem subsidence. Failure analysis of the 5 reinfections did not detect a clear pattern as to the cause of failure. CONCLUSION: We found that cementless 1-stage revision in chronic periprosthetic hip joint infections has low reinfection rates in selected patients and may be applicable as a first-line treatment.

Do patients care about higher flexion in total knee arthroplasty? A randomized, controlled, double-blinded trial.

BACKGROUND: Little information exists to support that patients care about flexion beyond what is needed to perform activities of daily living (ADL) after Total knee arthroplasty (TKA). The purpose of this study was to investigate if the achievement of a higher degree of knee flexion after TKA would result in a better patient perceived outcome. METHODS: The study is a randomized, double-blinded, controlled trial in which 36 patients (mean age: 67.2 yrs) undergoing one-stage bilateral TKA randomly received a standard cruciate-retaining (CR) TKA in one knee and a high-flex posterior-stabilized (PS) TKA in the contra lateral knee. At follow-up ROM, satisfaction, pain, "feel" of the knee and the abilities in daily activities were assessed. RESULTS: At 1-year follow-up we found an expected significantly higher degree of knee flexion of 7° in the high-flex knees (p = 0.001). The high-flex TKA's showed a mean active flexion of 121°. In both TKA's the median VAS pain score was 0, the median VAS satisfaction score was 9, and the median VAS score of the patient "feel" of the knee was 9 at 1-year follow-up. Further, there were no significant differences between the knees in the performance of daily activities. CONCLUSIONS: As expected the high-flex TKA showed increased knee flexion, but no significant differences in the patient perceived outcomes were found. This suggests little relevance to the patients of the difference in knee flexion - when flexion is of this magnitude - as pain free ROM and high patient satisfaction were achieved with both TKA's. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00294528.

Fast-track revision knee arthroplasty. A feasibility study.

BACKGROUND AND PURPOSE: Fast-track surgery has reduced the length of hospital stay (LOS), morbidity, and convalescence in primary hip and knee arthroplasty (TKA). We assessed whether patients undergoing revision TKA for non-septic indications might also benefit from fast-track surgery. METHODS: 29 patients were operated with 30 revision arthroplasties. Median age was 67 (34-84) years. All patients followed a standardized fast-track set-up designed for primary TKA. We determined the outcome regarding LOS, morbidity, mortality, and satisfaction. RESULTS: Median LOS was 2 (1-4) days excluding 1 patient, who was transferred to another hospital for logistical reasons (10 days). None of the patients died within 3 months, and 3 patients were re-admitted (2 for suspicion of DVT, which was not found, and 1 for joint mobilization). Patient satisfaction was high. INTERPRETATION: Patients undergoing revision TKA for non-septic reasons may be included in fast-track protocols. Outcome appears to be similar to that of primary TKA regarding LOS, morbidity, and satisfaction. Our findings call for larger confirmatory studies and studies involving other indications (revision THA, 1-stage septic revisions).

High-volume infiltration analgesia in bilateral hip arthroplasty. A randomized, double-blind placebo-controlled trial.

BACKGROUND AND PURPOSE: High-volume infiltration analgesia may be effective in postoperative pain management after hip arthroplasty but methodological problems prevent exact interpretation of previous studies. METHODS: In a randomized, double-blind placebo-controlled trial in 12 patients undergoing bilateral total hip arthroplasty (THA) in a fast-track setting, saline or high-volume (170 mL) ropivacaine (0.2%) with epinephrine (1:100,000) was administered to the wound intraoperatively along with supplementary postoperative injections via an intraarticular epidural catheter. Oral analgesia was instituted preoperatively with a multimodal regimen (gabapentin, celecoxib, and acetaminophen). Pain was assessed repeatedly for 48 hours postoperatively, at rest and with 45° hip flexion. RESULTS: Pain scores were low and similar between ropivacaine and saline administration. Median hospital stay was 4 (range 2-7) days. Interpretation Intraoperative high-volume infiltration with 0.2% ropivacaine with repeated intraarticular injections postoperatively may not give a clinically relevant analgesic effect in THA when combined with a multimodal oral analgesic regimen with gabapentin, celecoxib, and acetaminophen.

A compression bandage improves local infiltration analgesia in total knee arthroplasty.

BACKGROUND: High-volume local infiltration analgesia has been shown to be an effective pain treatment after knee replacement, but the role of bandaging to prolong analgesia has not been evaluated. METHODS: 48 patients undergoing fast-track total knee replacement with high-volume (170 mL) 0.2% ropivacaine infiltration analgesia were randomized to receive a compression or a non-compression bandage, and pain was assessed at rest and with mobilization at regular intervals for 24 h postoperatively. RESULTS: Pain at rest, during flexion, or on straight leg lift was lower for the first 8 h in patients with compression bandage than in those with non-compression bandage and with a similar low use of oxycodone. Mean hospital stay was similar (2.8 days and 3.3 days, respectively). INTERPRETATION: A compression bandage is recommended to improve analgesia after high-volume local infiltration analgesia in total knee arthroplasty.

Local anesthetics after total knee arthroplasty: intraarticular or extraarticular administration? A randomized, double-blind, placebo-controlled study.

BACKGROUND: High-volume local infiltration analgesia with additional intraarticular and wound administration of local anesthetic has been shown to be effective after knee replacement, but the optimum site of administration of the local anesthetic (i.e. intraarticular or extraarticular) has not been evaluated. PATIENTS AND METHODS: 32 patients undergoing total knee replacement with high-volume (170 mL) 0.2% ropivacaine infiltration analgesia were randomized to receive injection of 20 mL ropivacaine (0.2%) intraarticularly plus 30 mL saline in the extraarticular wound space 24 hours postoperatively or to receive 20 mL ropivacaine (0.2%) intraarticularly plus 30 mL ropivacaine (0.2%) in the extraarticular wound space 24 hours postoperatively. Pain intensity at rest and with mobilization was recorded for 4 hours after administration of additional local anesthetics. RESULTS: Intensity of pain at rest, during flexion, or straight leg lift was not statistically significantly different between the two groups, but there was a tendency of improved analgesia with administration of additional local anesthetic in the extraarticular wound space. INTERPRETATION: The optimal site of administration of local anesthetic in total knee arthroplasty cannot be determined from the present study. However, the insignificant analgesic effect from additional administration of extraarticular local anaesthetic may have been due to the relatively low pain scores observed 24 h postoperatively, confirming the efficiency of the high-volume infiltration analgesia technique. Further studies are required to define the optimal site of administration of local anesthetic following knee replacement surgery.

Indications for knee arthroplasty have remained consistent over time.

INTRODUCTION: Between 2004 and 2009, the incidence of primary total knee arthroplasty (TKA) in Denmark has almost doubled. It has been speculated that this increase may be a result of patients being operated on weaker indications. The purpose of this study was to compare preoperative degrees of osteoarthritis and health-related quality of life (QoL) in patients receiving primary TKA in 2004 and 2009. MATERIAL AND METHODS: We identified 154 and 369 primary TKAs inserted at our institution in 2004 and 2009, respectively. Patients had been invited to complete the Short Form (SF)-36 questionnaire preoperatively. Two groups of patients that were representative with regard to age and gender were randomly sampled and compared (n = 44 in 2004 versus n = 106 in 2009). The Kellgren-Lawrence (K-L) grade of osteoarthritis was assessed on preoperative radiographs in all patients. RESULTS: We found no statistically significant differences in gender distribution or mean age at surgery. We reached K-L grades of 3-4 in 52.4% and 49.6% in 2004 and 2009, respectively (p = 0.57). The preoperative mean SF-36 physical component scores were 32.6 and 33.7, respectively (p = 0.44). The preoperative mean SF-36 mental component scores were 43.0 in 2004 and 49.3 (i.e. 6.3 points higher) in 2009 (p = 0.003). CONCLUSION: Preoperative degrees of osteoarthritis and physical health-related QoL did not change from 2004 to 2009. Thus, it seems that these components of operative indications have not weakened. The increased preoperative SF-36 mental component score of these patients may have had a positive effect on postoperative outcomes. FUNDING: not relevant. TRIAL REGISTRATION: not relevant. TRIAL REGISTRATION: not relevant.

Bilateral simultaneous total hip arthroplasty in a fast track setting.

Simultaneous bilateral hip arthroplasty has been reported to have varying results in the literature when performed using conventional postoperative care. Unilateral hip and knee arthroplasty as well as bilateral simultaneous knee arthroplasty may be associated with reduced length of stay and low complication rates when performed in a fast-track setting. We believed it would be useful to assess hip arthroplasty in this context, and we report 50 consecutive fast-track simultaneous bilateral hip arthroplasty procedures. The median length of stay was 4 days. Mortality within 90 days was 4% and 8% required a further operative procedure. The overall complication rate was 22%. 55% of the complications were considered to be caused by failures in surgical technique and 45% by other factors. Bilateral simultaneous hip arthroplasty may have a high complication rate in a fast-track setting and further evaluation may be warranted.

Intraoperative local infiltration analgesia for early analgesia after total hip arthroplasty: a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND OBJECTIVES: High-volume local infiltration analgesia (LIA) is widely applied as part of a multimodal pain management strategy in total hip arthroplasty (THA). However, methodological problems hinder the exact interpretation of previous trials, and the evidence for LIA in THA remains to be clarified. Therefore, we evaluated whether intraoperative high-volume LIA, in addition to a multimodal oral analgesic regimen, would further reduce acute postoperative pain after THA. METHODS: Patients scheduled for unilateral, primary THA under spinal anesthesia were included in this randomized, double-blind, placebo-controlled trial receiving high-volume (150 mL) wound infiltration with ropivacaine 0.2% with epinephrine (10 µg/mL) or saline 0.9%. A multimodal oral analgesic regimen consisting of slow-release acetaminophen 2 g, celecoxib 400 mg, and gabapentin 600 mg was instituted preoperatively. Rescue analgesic consisted of oral oxycodone. Pain was assessed repeatedly the first 8 hrs after surgery using the 100-mm visual analog scale. The primary end point was pain during walking (5 m) 8 hrs after surgery. Secondary end points were pain at rest, pain on 45 degrees of passive flexion of the hip with the leg straight, and cumulative consumption of oxycodone. RESULTS: A total of 120 patients were included. Pain during walking (median [interquartile range] [95% confidence interval]) was low in the ropivacaine versus the placebo group (20 [14-38] [0-93] vs 22 [10-40] [0-83]) and did not differ significantly (P = 0.71). Consumption of rescue oxycodone (5 mg [0-10 mg] [0-24 mg] vs 10 mg [0-15 mg] [0-29 mg]) did not differ (P = 0.45). CONCLUSIONS: Intraoperative high-volume LIA with ropivacaine 0.2% provided no additional reduction in acute pain after THA when combined with a multimodal oral analgesic regimen consisting of acetaminophen, celecoxib, and gabapentin and is therefore not recommended.

Wound spread of radiolabeled saline with multi- versus few-hole catheters.

BACKGROUND AND OBJECTIVES: Continuous wound infusion of local anesthetics is effective in postoperative pain management and may be useful in major joint arthroplasty, but the optimal technique for postoperative administration of local anesthetics in the wound awaits trials evaluating the optimal type of catheter (single-, few-, or multiholed catheters). METHODS: Sixteen patients undergoing total hip arthroplasty were randomized to intraoperative subfascial placement of a triple-orifice epidural catheter or a 15-cm multiholed catheter. Twenty milliliters of technetium Tc 99m diethylenetriaminepentaacetic acid-labeled saline was injected postoperatively and wound spread for 10 mins was recorded with a double-head gamma camera. RESULTS: Mean (SD) wound spread (cm(2)) was the same with administration through a multiholed catheter versus the epidural catheter in both anterior (89 [15] versus 82 [20], P = 0.4) and lateral (68 [19] versus 60 [11], P = 0.3) projections. CONCLUSIONS: Wound spread of a bolus injection through 15-cm multiholed catheters versus triple-orifice epidural catheters is similar with subfascial catheter placement in total hip arthroplasty. Procedure-specific trials are required to evaluate the analgesic efficacy of postoperative administration of local anesthetic in the wound with different types of catheter before general recommendations can be made.