Citations 229

Anti-fibrotic effects of the antihistamine ketotifen in a rabbit model of arthrofibrosis

Bone & Joint Research | June 17, 2020 | Volume: 9 | Issue: 6 | Pages: 302-310

10.1302/2046-3758.96.bjr-2019-0272.r2 | PMID 32728431

Aims Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310.
Comparative analysis of 23 synovial fluid biomarkers for hip and knee periprosthetic joint infection detection

Journal of Orthopaedic Research | June 2, 2020 | Volume: 38 | Issue: 12 | Pages: 2664-2674

10.1002/jor.24766 | PMID 32485031

AbstractThere is interest in novel synovial fluid biomarkers for the detection of periprosthetic joint infection (PJI). Here, we assessed the diagnostic accuracy of 23 simple or sophisticated synovial fluid biomarkers for periprosthetic hip or knee infection detection. One hundred seven subjects were studied, 57 of whom had aseptic failure (AF) and 50 PJI. The following synovial fluid biomarkers were tested using spectrophotometric assays, immunoassays, lateral flow tests, or test strips: leukocyte count, monocyte percentage, lymphocyte percentage, neutrophil percentage, C‐reactive protein (CRP), glucose, lactate, granulocyte‐macrophage colony‐stimulating factor, interferon‐γ, interleukin‐1β (IL‐1β), IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐13, IL‐17A, IL‐23, tumor necrosis factor‐α, α‐defensin, and leukocyte esterase. The best‐performing synovial fluid biomarkers to differentiate PJI from AF—that is, those with highest area under the curve compared to all other biomarkers—were leukocyte count, percent neutrophils and percent monocytes, CRP, and α‐defensin (P < .0001).
Antimicrobial properties of antibiotic-loaded implants

The Bone & Joint Journal | May 31, 2020 | Volume: 102-B | Issue: 6_Supple_A | Pages: 158-162

10.1302/0301-620x.102b6.bjj-2019-1636.r1 | PMID 32475268

Aims The aim of this study was to compare the ability of tantalum, 3D porous titanium, antibiotic-loaded bone cement, and smooth titanium alloy to inhibit staphylococci in an in vitro environment, based on the evaluation of the zone of inhibition (ZOI). The hypothesis was that there would be no significant difference in the inhibition of methicillin-sensitive or methicillin-resistant Staphylococcus aureus (MSSA/MRSA) between the two groups. Methods A total of 30 beads made of three different materials (tantalum/3D porous titanium and smooth titanium alloy) were bathed for one hour in a solution of 1 g vancomycin in 20 ml of sterile water for injection (bath concentration: 50 mg/mL). Ten 1 cm3 cylinders of antibiotic-loaded cement were also created by mixing standard surgical cement with 1 g of vancomycin in standardized sterile moulds. The cylinders were then placed on agar plates inoculated with MSSA and MRSA. The ZOIs were measured each day and the cylinders were transferred onto a new inoculated plate. Results For MSSA and MRSA, no inhibitory effect was found in the control group, and antibiotic-loaded smooth titanium alloy beads showed a short inhibitory effect until day 2. For MSSA, both tantalum and 3D porous titanium beads showed significantly larger mean ZOIs than cement beads (all p < 0.01) each day until day 7 for tantalum and until day 3 for 3D porous titanium. After six days, antibiotic-loaded cement had significantly larger mean ZOIs than the 3D porous titanium (p = 0.027), but no significant difference was found with tantalum (p = 0.082). For MRSA, both tantalum and 3D porous titanium beads had significantly larger mean ZOIs than antibiotic-loaded cement each day until day 6 for tantalum (all p < 0.01) and until day 3 for 3D porous titanium (all p < 0.04). Antibiotic-loaded cement had significantly larger mean ZOIs than tantalum and 3D porous titanium from day 7 to 9 (all p < 0.042). Conclusion These results show that porous metal implants can deliver local antibiotics over slightly varying time frames based on in vitro analysis. Cite this article: Bone Joint J 2020;102-B(6 Supple A):158–162.
Two-stage arthrodesis for complex, failed, infected total knee arthroplasty

The Bone & Joint Journal | May 31, 2020 | Volume: 102-B | Issue: 6_Supple_A | Pages: 170-175

10.1302/0301-620x.102b6.bjj-2019-1554.r1 | PMID 32475264

Aims Arthrodesis is rarely used as a salvage procedure for patients with a chronically infected total knee arthroplasty (TKA), and little information is available about the outcome. The aim of this study was to assess the reliability, durability, and safety of this procedure as the definitive treatment for complex, chronically infected TKA, in a current series of patients. Methods We retrospectively identified 41 patients (41 TKAs) with a complex infected TKA, who were treated between 2002 and 2016 using a deliberate, two-stage knee arthrodesis. Their mean age was 64 years (34 to 88) and their mean body mass index (BMI) was 39 kg/m2 (25 to 79). The mean follow-up was four years (2 to 9). The extensor mechanism (EM) was deficient in 27 patients (66%) and flap cover was required in 14 (34%). Most patients were host grade B (56%) or C (29%), and limb grade 3 (71%), according to the classification of McPherson et al. A total of 12 patients (29%) had polymicrobial infections and 20 (49%) had multi-drug resistant organisms; fixation involved an intramedullary nail in 25 (61%), an external fixator in ten (24%), and dual plates in six (15%). Results Survivorship free from amputation, persistent infection, and reoperation, other than removal of an external fixator, at five years was 95% (95% confidence interval (CI) 89% to 100%), 85% (95% CI 75% to 95%), and 64% (95% CI 46% to 82%), respectively. Reoperation, other than removal of an external fixator, occurred in 13 patients (32%). After the initial treatment, radiological nonunion developed in ten knees (24%). Nonunion was significantly correlated with persistent infection (p = 0.006) and external fixation (p = 0.005). Of those patients who achieved limb salvage, 34 (87%) remained mobile and 31 (79%) had ‘absent’ or ‘minimal’ pain ratings. Conclusion Knee arthrodesis using a two-stage protocol achieved a survivorship free from amputation for persistent infection of 95% at five years with 87% of patients were mobile at final follow-up. However, early reoperation was common (32%). This is not surprising as this series included worst-case infected TKAs in which two-thirds of the patients had a disrupted EM, one-third required flap cover, and most had polymicrobial or multi-drug resistant organisms. Cite this article: Bone Joint J 2020;102-B(6 Supple A):170–175.
Excellent two-year survivorship of 3D-printed metaphyseal cones in revision total knee arthroplasty

The Bone & Joint Journal | May 31, 2020 | Volume: 102-B | Issue: 6_Supple_A | Pages: 107-115

10.1302/0301-620x.102b6.bjj-2019-1544.r1 | PMID 32475272

AimsMetaphyseal fixation during revision total knee arthroplasty (TKA) is important, but potentially difficult when using historical designs of cone. Material and manufacturing innovations have improved the size and shape of the cones which are available, and simplified the required bone preparation. In a large series, we assessed the implant survivorship, radiological results, and clinical outcomes of new porous 3D-printed titanium metaphyseal cones featuring a reamer-based system.MethodsWe reviewed 142 revision TKAs in 139 patients using 202 cones (134 tibial, 68 femoral) which were undertaken between 2015 and 2016. A total of 60 involved tibial and femoral cones. Most cones (149 of 202; 74%) were used for Type 2B or 3 bone loss. The mean age of the patients was 66 years (44 to 88), and 76 (55 %) were female. The mean body mass index (BMI) was 34 kg/m2(18 to 60). The patients had a mean of 2.4 (1 to 8) previous operations on the knee, and 68 (48%) had a history of prosthetic infection. The mean follow-up was 2.4 years (2 to 3.6).ResultsSurvivorship free of cone revision for aseptic loosening was 100% and survivorship free of any cone revision was 98%. Survivorships free of any revision and any reoperation were 90% and 83%, respectively. Five cones were revised: three for infection, one for periprosthetic fracture, and one for aseptic tibial loosening. Radiologically, three unrevised femoral cones appeared loose in the presence of hinged implants, while the remaining cones appeared stable. All cases of cone loosening occurred in patients with Type 2B or 3 defects. The mean Knee Society score (KSS) improved significantly from 50 (0 to 94) preoperatively to 87 (72 to 94) (p < 0.001). Three intraoperative fractures with cone impaction (two femoral, one tibial) healed uneventfully.ConclusionNovel 3D-printed titanium cones, with a reamer-based system, yielded excellent early survivorship and few complications in patients with severe bone loss undergoing difficult revision TKA. The diversity of cone options, relative ease of preparation, and outcomes rivalling those of previous designs of cone support their continued use. Cite this article: Bone Joint J 2020;102-B(6 Supple A):107–115.
Outcomes of a technique combining diaphyseal impaction grafting and metaphyseal cones for severe bone loss in revision total knee arthroplasty

The Bone & Joint Journal | May 31, 2020 | Volume: 102-B | Issue: 6_Supple_A | Pages: 116-122

10.1302/0301-620x.102b6.bjj-2019-1511.r1 | PMID 32475283

Aims Metaphyseal cones with cemented stems are frequently used in revision total knee arthroplasty (TKA). However, if the diaphysis has been previously violated, the resultant sclerotic canal can impair cemented stem fixation, which is vital for bone ingrowth into the cone, and long-term fixation. We report the outcomes of our solution to this problem, in which impaction grafting and a cemented stem in the diaphysis is combined with an uncemented metaphyseal cone, for revision TKA in patients with severely compromised bone. Methods A metaphyseal cone was combined with diaphyseal impaction grafting and cemented stems for 35 revision TKAs. There were two patients with follow-up of less than two years who were excluded, leaving 33 procedures in 32 patients in the study. The mean age of the patients at the time of revision TKA was 67 years (32 to 87); 20 (60%) were male. Patients had undergone a mean of four (1 to 13) previous knee arthroplasty procedures. The indications for revision were aseptic loosening (80%) and two-stage reimplantation for prosthetic joint infection (PJI; 20%). The mean follow-up was four years (2 to 11). Results Survival free from revision of the cone/impaction grafting construct due to aseptic loosening was 100% at five years. Survival free from any revision of the construct and free from any reoperation were 92% and 73% at five years, respectively. A total of six patients (six TKAs, 17%) required a further revision, four for infection or wound issues, and two for periprosthetic fracture. Radiologically, one unrevised TKA had evidence of loosening which was asymptomatic. In all unrevised TKAs the impacted diaphyseal bone graft appeared to be incorporated radiologically. Conclusion When presented with a sclerotic diaphysis and substantial metaphyseal bone loss, this technique combining diaphyseal impaction grafting with a metaphyseal cone provided near universal success in relation to implant fixation. Moreover, radiographs revealed incorporation of the bone graft and biological fixation of the cone. While long-term follow-up will be important, this technique provides an excellent option for the management of complex revision TKAs. Cite this article: Bone Joint J 2020;102-B(6 Supple A):116–122.
Constrained Liners Implanted Simultaneously at the Time of Acetabular Shell Revision with a Highly Porous Implant

Journal of Bone and Joint Surgery | May 26, 2020 | Volume: 102 | Issue: 17 | Pages: 1521-1529

10.2106/jbjs.19.01332 | PMID 32453110

Background: Many surgeons are reluctant to use a constrained liner at the time of acetabular component revision because of concerns that doing so might result in early acetabular component loosening related to high bone-implant interface stresses transmitted from the constrained liner. We hypothesized that, with appropriate initial implant stabilization using highly porous acetabular components with robust supplemental screw fixation, constrained liners could be safely used at the time of acetabular revision. Methods: We retrospectively identified 148 revision total hip arthroplasties (THAs) in which a constrained liner of 1 design was cemented into a newly placed highly porous acetabular component fixed with supplemental screws (mean, 5 screws). The mean age at the time of revision THA was 69 years, and 68% of the patients were female. The most common indications for revision were 2-stage reimplantation (33%), recurrent dislocation (30%), and aseptic loosening of the acetabular component (22%) or both the acetabular and femoral components (9%). The mean duration of follow-up was 7 years. Results: There were no failures at the bone-implant interface. No cases of acetabular metal shell loosening were identified on radiographic analysis. The 10-year survival rates with acetabular revision and any reoperation as the end points were 75% and 67%, respectively. Overall, 33 hips (22%) required revision or reoperation because of infection or wound complications (n = 12), dislocation or mechanical failure of the constrained liner (n = 11), periprosthetic femoral fracture (n = 4), femoral loosening (n = 3), or other reasons (n = 3). The 10-year survival rate with re-revision for instability as the end point was 88% overall, which was similar to the 85% 10-year survival rate with re-revision for instability as the end point among hips that were specifically revised because of instability during index revision THA (p = 0.9). Conclusions: Implanting a constrained liner at the time of acetabular revision in high-risk patients resulted in no cases of aseptic metal acetabular component loosening in this large series. This finding is likely related to the fact that a highly porous acetabular component was utilized with robust supplemental screw fixation in each case. Such information is valuable as these data favor a paradigm shift when compared with some traditionally held tenets. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.
Comparison of Porous Tantalum Acetabular Implants and Harrington Reconstruction for Metastatic Disease of the Acetabulum

Journal of Bone and Joint Surgery | May 26, 2020 | Volume: 102 | Issue: 14 | Pages: 1239-1247

10.2106/jbjs.19.01189 | PMID 32675673

Background: The periacetabular region is a common location for metastatic disease. Although large lytic acetabular defects are commonly treated with a hip arthroplasty with a cemented component according to a Harrington-style reconstruction, the use of highly porous uncemented tantalum acetabular components has been described. Currently, there are no direct comparisons of these reconstructive techniques. The purpose of this study was to compare the outcomes of the Harrington technique and tantalum acetabular component reconstruction for periacetabular metastases. Methods: From 2 tertiary sarcoma centers, we retrospectively reviewed 115 patients (70 female and 45 male) with an acetabular metastatic defect who had been treated between 2002 and 2015 with a total hip arthroplasty using either the cemented Harrington technique (78 patients) or a tantalum acetabular reconstruction (37 patients). The mean patient age was 61 years, and the most common Eastern Cooperative Oncology Group status was 3 (39 patients). The mean follow-up for surviving patients was 4 years. Results: An additional surgical procedure was performed in 24 patients (21%). Harrington-style reconstructions were more likely to require a reoperation compared with tantalum reconstructions (hazard ratio [HR], 4.59; p = 0.003). The acetabular component was revised in 13 patients (11%); 5 patients (4%) underwent revisions that were due to loosening of the acetabular component. The 10-year cumulative incidence of revision of the acetabular component for loosening was 9.6% in the Harrington group and 0% in the tantalum group (p = 0.09). The mean Harris hip score significantly improved following reconstruction (31 to 67 points; p < 0.001), with no significant difference (p = 0.29) between groups. Conclusions: In patients with periacetabular metastatic disease treated with total hip arthroplasty, an acetabular reconstruction strategy utilizing highly porous tantalum acetabular components and augments successfully provided patients with a more durable construct with fewer complications compared with the cemented Harrington-style technique. Levels of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.
Primary and revision total hip arthroplasty with uncemented acetabular components in patients with Paget’s disease

HIP International | April 28, 2020 | Volume: 32 | Issue: 1 | Pages: 67-72

10.1177/1120700020920178 | PMID 32340487

Introduction: Paget’s disease affects 3–4% of the population; however, literature describing outcomes of total hip arthroplasty (THA) in this population are limited. Given the known concerns with bleeding, heterotopic ossification (HO), and component loosening, we describe our results with primary and revision THAs in Paget’s disease with emphasis on implant survivorship, radiographic results, and clinical outcomes. Methods: We identified 25 THAs performed with contemporary uncemented acetabular components in patients with Paget’s disease from 1999 to 2014. Mean age and follow-up were 78 and 7 years. Results: In primary THAs, survivorship free from aseptic acetabular and femoral loosening was 100% and 94% at 8 years. 7 patients (41%) received blood transfusions. HO was seen in 9 (53%). Mean Harris Hip Score (HHS) improved from 49 to 76. In revision THAs, survivorship free from acetabular and/or femoral aseptic loosening was 100% at 5 years. 3 patients (38%) received a transfusion. HO was seen in 5 (63%). Mean HHS improved from 52 to 77. There were no radiographic signs of aseptic loosening among unrevised cases in either group. Discussion: Our investigation demonstrates that concerns with acetabular fixation in Paget’s disease have been mitigated with contemporary uncemented acetabular components. Complications previously noted, namely intraoperative bleeding and HO, continue to be of concern.
Neuraxial anesthesia is associated with improved survival after total joint arthroplasty depending on frailty: a cohort study

Regional Anesthesia & Pain Medicine | April 8, 2020 | Volume: 45 | Issue: 6 | Pages: 405-411

10.1136/rapm-2019-101250 | PMID 32269138

Background Frailty increases risk for complications after total joint arthroplasty (TJA). Whether this association is influenced by anesthetic administered is unknown. We hypothesized that use of neuraxial (spinal or epidural) anesthesia is associated with better outcomes compared with general anesthesia, and that the effect of anesthesia type on outcomes differs by frailty status. Methods This single-institution cohort study included all patients (≥50 years) from January 2005 through December 2016 undergoing unilateral, primary and revision TJA. Using multivariable Cox regression, we assessed relationships between anesthesia type, a preoperative frailty deficit index (FI) categorized as non-frail (FI <0.11), vulnerable (FI 0.11 to 0.20), and frail (FI >0.20), and complications (mortality, infection, wound complications/hematoma, reoperation, dislocation, and periprosthetic fracture) within 1 year after surgery. Interactions between anesthesia type and frailty were tested, and stratified models were presented when an interaction (p<0.1) was observed. Results Among 18 458 patients undergoing TJA, more patients were classified as frail (21.5%) and vulnerable (36.2%) than non-frail (42.3%). Anesthesia type was not associated with complications after adjusting for age, joint, and revision type. However, in analyzes stratified by frailty, vulnerable patients under neuraxial block had less mortality (HR=0.49; 95% CI 0.27 to 0.89) and wound complications/hematoma (HR=0.71; 95% CI 0.55 to 0.90), whereas no difference in risk by anesthesia type was observed among patients found non-frail or frail. Conclusions Neuraxial anesthesia use among vulnerable patients was associated with improved survival and less wound complications. Calculating preoperative frailty prior to TJA informs perioperative risk and enhances shared-decision making for selection of anesthesia type.