Limberg, Afton K.

Background: Two-stage exchange arthroplasty with a high-dose antibiotic-loaded bone cement (ALBC) spacer and intravenous or oral antibiotics is the most common method of managing a periprosthetic joint infection (PJI) after a total knee arthroplasty (TKA). However, little is known about the contemporary incidence, the risk factors, and the outcomes of acute kidney injuries (AKIs) in this cohort. Methods: We identified 424 patients who had been treated with 455 ALBC spacers after resection of a PJI following a primary TKA from 2000 to 2017. The mean age at resection was 67 years, the mean body mass index (BMI) was 33 kg/m 2 , 47% of the patients were women, and 15% had preexisting chronic kidney disease (CKD). The spacers (87% nonarticulating) contained a mean of 8 g of vancomycin and 9 g of an aminoglycoside per construct (in situ for a mean of 11 weeks). Eighty-six spacers also had amphotericin B (mean, 412 mg). All of the patients were concomitantly treated with systemic antibiotics for a mean of 6 weeks. An AKI was defined as a creatinine level of ≥1.5 times the baseline or an increase of ≥0.3 mg/dL within any 48-hour period. The mean follow-up was 6 years (range, 2 to 17 years). Results: Fifty-four AKIs occurred in 52 (14%) of the 359 patients without preexisting CKD versus 32 AKIs in 29 (45%) of the 65 patients with CKD (odds ratio [OR], 5; p = 0.0001); none required acute dialysis. Overall, when the vancomycin concentration or aminoglycoside concentration was >3.6 g/batch of cement, the risk of AKI increased (OR, 1.9 and 1.8, respectively; p = 0.02 for both). Hypertension (β = 0.17; p = 0.002), perioperative hypovolemia (β = 0.28; p = 0.0001), and acute atrial fibrillation (β = 0.13; p = 0.009) were independent predictors for AKI in patients without preexisting CKD. At the last follow-up, 8 patients who had sustained an AKI had progressed to CKD, 4 of whom received dialysis. Conclusions: In our study, the largest series to date that we are aware of regarding this issue, AKI occurred in 14% of patients with normal renal function at baseline, and 2% developed CKD after undergoing a 2-stage exchange arthroplasty for a PJI after TKA. However, the risk of AKI was fivefold greater in those with preexisting CKD. The causes of acute renal blood flow impairment were independent predictors for AKI. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Debate remains regarding the utility of mechanical axis alignment as a predictor of durability after total knee arthroplasty (TKA). Our study aimed to assess the effects of coronal alignment on implant durability, clinical outcomes, and radiographic results with a single fixed-bearing TKA design. All patients undergoing primary cemented TKA of a single design (Stryker Triathlon) from 2005–2007 with >10 years of follow-up and available pre-operative and post-operative hip–knee–ankle radiographs were included (n = 89). Radiographs were measured to determine coronal alignment and assessed for loosening. Mean preoperative mechanical axis alignment was −6° ± 6.7° (varus, range, −16°–23°), while mean post-operative alignment was −1° ± 2.7° (varus, range, −3°–15°). The aligned group was defined as knees with a post-operative mechanical axis of 0° ± 3° (n = 73) and the outlier group as those outside this range (n = 16). No patients underwent revision. Ten-year survivorship free from any reoperation was 99% and 100% in the aligned and outlier groups, respectively (p = 0.64). Knee Society scores improved significantly in both groups (p < 0.001) and did not differ at final follow-up (p = 0.15). No knees demonstrated radiographic evidence of loosening. Post-operative mechanical axis alignment within 3° of neutral was not associated with improved implant durability, clinical outcomes, or radiographic results at 10 years following primary TKA.

(1) Background: Arthrofibrosis is a common cause of patient debility and dissatisfaction after total knee arthroplasty (TKA). The diversity of molecular pathways involved in arthrofibrosis disease progression suggest that effective treatments for arthrofibrosis may require a multimodal approach to counter the complex cellular mechanisms that direct disease pathogenesis. In this study, we leveraged RNA-seq data to define genes that are suppressed in arthrofibrosis patients and identified adiponectin (ADIPOQ) as a potential candidate. We hypothesized that signaling pathways activated by ADIPOQ and the cognate receptors ADIPOR1 and ADIPOR2 may prevent fibrosis-related events that contribute to arthrofibrosis. (2) Methods: Therefore, ADIPOR1 and ADIPOR2 were analyzed in a TGFβ1 inducible cell model for human myofibroblastogenesis by both loss- and gain-of-function experiments. (3) Results: Treatment with AdipoRon, which is a small molecule agonist of ADIPOR1 and ADIPOR2, decreased expression of collagens (COL1A1, COL3A1, and COL6A1) and the myofibroblast marker smooth muscle α-actin (ACTA2) at both mRNA and protein levels in basal and TGFβ1-induced cells. (4) Conclusions: Thus, ADIPOR1 and ADIPOR2 represent potential drug targets that may attenuate the pathogenesis of arthrofibrosis by suppressing TGFβ-dependent induction of myofibroblasts. These findings also suggest that AdipoRon therapy may reduce the development of arthrofibrosis by mediating anti-fibrotic effects in joint capsular tissues.

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.

AimsVarus-valgus constrained (VVC) implants are often used during revision total knee arthroplasty (TKA) to gain coronal plane stability. However, the increased mechanical torque applied to the bone-cement interface theoretically increases the risk of aseptic loosening. We assessed mid-term survivorship, complications, and clinical outcomes of a fixed-bearing VVC device in revision TKAs.MethodsA total of 416 consecutive revision TKAs (398 patients) were performed at our institution using a single fixed-bearing VVC TKA from 2007 to 2015. Mean age was 64 years (33 to 88) with 50% male (199). Index revision TKA diagnoses were: instability (n = 122, 29%), aseptic loosening (n = 105, 25%), and prosthetic joint infection (PJI) (n = 97, 23%). All devices were cemented on the epiphyseal surfaces. Femoral stems were used in 97% (n = 402) of cases, tibial stems in 95% (n = 394) of cases; all were cemented. In total, 93% (n = 389) of cases required a stemmed femoral and tibial component. Femoral cones were used in 29%, and tibial cones in 40%. Survivorship was assessed via competing risk analysis; clinical outcomes were determined using Knee Society Scores (KSSs) and range of movement (ROM). Mean follow-up was four years (2 to 10).ResultsThe five-year cumulative incidence of subsequent revision for aseptic loosening and instability were 2% (95% confidence interval (CI) 0.2 to 3, number at risk = 154) and 4% (95% CI 2 to 6, number at risk = 153), respectively. The five-year cumulative incidence of any subsequent revision was 14% (95% CI 10 to 18, number at risk = 150). Reasons for subsequent revision included PJI (n = 23, of whom 12 had previous PJI), instability (n = 13), and aseptic loosening (n = 11). The use of this implant without stems was found to be a significant risk factor for subsequent revision (hazard ratio (HR) 7.58 (95% CI 3.98 to 16.03); p = 0.007). KSS improved from 46 preoperatively to 81 at latest follow-up (p < 0.001). ROM improved from 96° prerevision to 108° at latest follow-up (p = 0.016).ConclusionThe cumulative incidence of subsequent revision for aseptic loosening and instability was very low at five years with this fixed-bearing VVC implant in revision TKAs. Routine use of cemented and stemmed components with targeted use of metaphyseal cones likely contributed to this low rate of aseptic loosening. Cite this article: Bone Joint J 2020;102-B(4):458–462.

AbstractThe dense formation of abnormal scar tissue after total knee arthroplasty results in arthrofibrosis, an unfortunate sequela of inflammation. The purpose of this study was to use a validated rabbit model to assess the effects on surgically‐induced knee joint contractures of two combined pharmacological interventions: celecoxib (CXB) loaded on an implanted collagen membrane, and subcutaneously (SQ) injected ketotifen. Thirty rabbits were randomly divided into five groups. The first group received no intervention after the index surgery. The remaining four groups underwent intra‐articular implantation of collagen membranes loaded with or without CXB at the time of the index surgery; two of which were also treated with SQ ketotifen. Biomechanical joint contracture data were collected at 8, 10, 16, and 24 weeks. At the time of necropsy (24 weeks), posterior capsule tissue was collected for messenger RNA and histopathologic analyses. At 24 weeks, there was a statistically significant increase in passive extension among rabbits in all groups treated with CXB and/or ketotifen compared to those in the contracture control group. There was a statistically significant decrease in COL3A1, COL6A1, and ACTA2 gene expression in the treatment groups compared to the contracture control group (P < .001). Histopathologic data also demonstrated a trend towards decreased fibrous tissue density in the CXB membrane group compared to the vehicle membrane group. The present data suggest that intra‐articular placement of a treated collagen membrane blunts the severity of contracture development in a rabbit model of arthrofibrosis, and that ketotifen and CXB may independently contribute to the prevention of arthrofibrosis. Statement of clinical significance: Current literature has demonstrated that arthrofibrosis may affect up to 5% of primary total knee arthroplasty patients. For that reason, novel pharmacologic prophylaxis and treatment modalities are critical to mitigating reoperations and revisions while improving the quality of life for patients with this debilitating condition.

ABSTRACTArthrofibrosis is a common complication following total knee arthroplasty caused by pathologic fibroblast activation and excessive collagen deposition around a synovial joint leading to debilitating loss of motion. Treatment options are limited because the pathologic mechanisms remain to be characterized. Dysregulation of the inflammatory cascade may lead to communication between myofibroblasts and immune cells triggering tissue metaplasia, and excessive collagen deposition described clinically as arthrofibrosis. We explored the novel use of celecoxib (selective cyclooxygenase‐2 [COX‐2] inhibitor) to disrupt the downstream effects of the post‐traumatic inflammatory cascade and inhibit scar tissue formation in a validated rabbit model of arthrofibrosis combined with new parameters for quantifying the stiffness of the posterior capsule. Biomechanical and molecular analyses, of contracted rabbit knee posterior capsule tissue after COX‐2 inhibition revealed increased maximal passive extension and down‐regulation of collagen messenger RNA compared with controls. Histopathologic examination suggested a trend of decreased quantities of dense fibrous connective tissue with COX‐2 inhibition. These data may suggest that inhibiting the inflammatory cascade could potentially reduce pathologic myofibroblast activation, thereby reducing scar tissue formation and increasing the range of motion in arthrofibrotic joints. Implementing a multi‐modal pharmacologic approach may simultaneously target numerous cellular components contributing to the complex process of arthrofibrogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2609–2620, 2019

Background: Stiffness is a common reason for suboptimal clinical outcomes after primary total knee arthroplasty (pTKA). There is a lack of consensus regarding its definition, which is often conflated with its histopathologic subcategory—i.e., arthrofibrosis. There is value in refining the definition of acquired idiopathic stiffness in an effort to select for patients with arthrofibrosis. We conducted a systematic review and meta-analysis to establish a consensus definition of acquired idiopathic stiffness, determine its prevalence after pTKA, and identify potential risk factors for its development. Methods: MEDLINE, Embase, Cochrane Controlled Register of Trials (CENTRAL), and Scopus databases were searched from 2002 to 2017. Studies that included patients with stiffness after pTKA were screened with strict inclusion and exclusion criteria to isolate the subset of patients with acquired idiopathic stiffness unrelated to known extrinsic or surgical causes. Three authors independently assessed study eligibility and risk of bias and collected data. Outcomes of interest were then analyzed according to age, sex, and body mass index (BMI). Results: In the 35 included studies (48,873 pTKAs), the mean patient age was 66 years. In 63% of the studies, stiffness was defined as a range of motion of <90° or a flexion contracture of >5° at 6 to 12 weeks postoperatively. The prevalence of acquired idiopathic stiffness after pTKA was 4%, and this did not differ according to age (4%, I 2 = 95%, among patients <65 years old and 5%, I 2 = 96%, among those ≥65 years old; p = 0.238). The prevalence of acquired idiopathic stiffness was significantly lower in males (1%, I 2 = 85%) than females (3%, I 2 = 95%) (p < 0.0001) as well as in patients with a BMI of <30 kg/m 2 (2%, I 2 = 94%) compared with those with a BMI of ≥30 kg/m 2 (5%, I 2 = 97%) (p = 0.027). Conclusions: Contemporary literature supports the following definition for acquired idiopathic stiffness: a range of motion of <90° persisting for >12 weeks after pTKA in patients in the absence of complicating factors including preexisting stiffness. The mean prevalence of acquired idiopathic stiffness after pTKA was 4%; females and obese patients were at increased risk. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background: Some prior reports of total knee arthroplasty after high tibial osteotomy have shown high rates of aseptic loosening. As such, the goal of this study was to analyze the outcomes of contemporary total knee arthroplasty after high tibial osteotomy, with particular emphasis on survivorship free from aseptic loosening, any revision, and any reoperation; complications; radiographic results; and clinical outcomes. Methods: We retrospectively reviewed 207 patients who underwent 231 total knee arthroplasties using cemented prostheses after high tibial osteotomy from 2000 to 2012 through our total joint registry: 87% were after a closing-wedge osteotomy and 13% were after an opening-wedge osteotomy. The mean follow-up from total knee arthroplasty was 8 years. At the time of the total knee arthroplasty, the mean age was 64 years and the mean body mass index was 31 kg/m 2 . The majority of total knee arthroplasties had a posterior-stabilized design (93%), and 4% had a varus-valgus constraint design. Tibial stems were utilized in 8% of cases. Bivariate and multivariate Cox regression analyses were utilized to analyze risk factors for poorer survival. Results: At 10 years, survivorship free from aseptic loosening was 97%, survivorship free from any revision was 90%, and survivorship free from any reoperation was 85%. Fifteen patients (15 total knee arthroplasties [6%]) underwent aseptic revision, most commonly for instability (3%), aseptic loosening (2%), and periprosthetic fracture (1%). On bivariate analysis, patient age of <60 years was a significant risk factor for poorer revision-free survival (hazard ratio, 2.9; p = 0.02); on multivariate analysis, younger age was the only significant risk factor for revision (p = 0.04). There were 14 complications (6%), the most common being a manipulation under anesthesia in 9 cases (4%). No unrevised total knee arthroplasties had definitive radiographic evidence of loosening. Knee Society scores improved from a mean preoperative score of 59 points to a mean postoperative score of 93 points (p < 0.001). Conclusions: Contemporary total knee arthroplasty with a cemented prosthesis after high tibial osteotomy demonstrated excellent long-term durability, with 10-year survivorship free from aseptic loosening of 97%. There was reliable improvement in clinical outcomes, but perfect knee balance was sometimes challenging, as reflected by a 4% prevalence of manipulation under anesthesia and a 3% prevalence of revision for instability. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

AimsThere is little literature about total knee arthroplasty (TKA) after distal femoral osteotomy (DFO). Consequently, the purpose of this study was to analyze the outcomes of TKA after DFO, with particular emphasis on: survivorship free from aseptic loosening, revision, or any re-operation; complications; radiological results; and clinical outcome.Patients and MethodsWe retrospectively reviewed 29 patients (17 women, 12 men) from our total joint registry who had undergone 31 cemented TKAs after a DFO between 2000 and 2012. Their mean age at TKA was 51 years (22 to 76) and their mean body mass index 32 kg/m2(20 to 45). The mean time between DFO and TKA was ten years (2 to 20). The mean follow-up from TKA was ten years (2 to 16). The prostheses were posterior-stabilized in 77%, varus-valgus constraint (VVC) in 13%, and cruciate-retaining in 10%. While no patient had metaphyseal fixation (e.g. cones or sleeves), 16% needed a femoral stem.ResultsThe ten-year survivorship was 95% with aseptic loosening as the endpoint, 88% with revision for any reason as the endpoint, and 81% with re-operation for any reason as the endpoint. Three TKAs were revised for instability (n = 2) and aseptic tibial loosening (n = 1). No femoral component was revised for aseptic loosening. Patients under the age of 50 years were at greater risk of revision for any reason (hazard ratio 7; p = 0.03). There were two additional re-operations (6%) and four complications (13%), including three manipulations under anaesthetic (MUA; 10%). The Knee Society scores improved from a mean of 50 preoperatively (32 to 68) to a mean of 93 postoperatively (76 to 100; p < 0.001).ConclusionA cemented posterior-stabilized TKA has an 88% ten-year survivorship with revision for any reason as the endpoint. No femoral component was revised for aseptic loosening. Patients under the age of 50 years have a greater risk of revision. The clinical outcome was significantly improved but balancing the knee was challenging in 13% of TKAs requiring VVC. Overall, 10% of TKAs needed an MUA, and 6% of TKAs were revised for instability. Cite this article: Bone Joint J 2019;101-B:660–666.