Salib, Christopher G.

Background: Total knee arthroplasties (TKAs) with cementless fixation have been studied in multiple series with varying success. The aim of this study was to prepare a systematic review of the literature to evaluate clinical outcomes and revtpdelision rates of patients undergoing contemporary cementless TKA. Methods: A search of PubMed and MEDLINE was conducted for English-language articles published between 2005 and 2018 to identify studies examining survivorship and clinical outcomes of cementless TKAs. Studies that reported clinical and/or radiographic outcomes were included. Data collected included the number of TKAs, implant utilized, primary diagnosis, mean age and follow-up, implant survivorship, complications, revisions, and clinical outcome scores. All hybrid constructs and revision TKAs were excluded. Poisson regression analysis was used to determine the revision incidence rates per 1,000 person-years. Results: Forty-three studies with 10,447 TKAs met inclusion criteria, of which 8,187 were primary cementless TKAs. The mean follow-up was 7 years. The revision incidence per 1,000 person-years was 4.8 for all cementless designs. The complication rate for all cementless TKAs was 6%, with deep venous thrombosis being the most common complication. The mean postoperative Knee Society Score and Functional Score were 92 and 83, respectively. Conclusions: While newer-generation cementless designs have shown improved survivorship and clinical outcomes compared with earlier-generation cementless designs, the literature for cementless designs remains limited when compared with cemented designs. Further studies are needed to determine if cementless TKA can achieve the same benefits that have been realized with cementless total hip arthroplasty. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

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.

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.

Aims Concurrent hip and spine pathologies can alter the biomechanics of spinopelvic mobility in primary total hip arthroplasty (THA). This study examines how differences in pelvic orientation of patients with spine fusions can increase the risk of dislocation risk after THA. Patients and Methods We identified 84 patients (97 THAs) between 1998 and 2015 who had undergone spinal fusion prior to primary THA. Patients were stratified into three groups depending on the length of lumbar fusion and whether or not the sacrum was involved. Mean age was 71 years (40 to 87) and 54 patients (56%) were female. The mean body mass index (BMI) was 30 kg/m2 (19 to 45). Mean follow-up was six years (2 to 17). Patients were 1:2 matched to patients with primary THAs without spine fusion. Hazard ratios (HR) were calculated. Results Dislocation in the fusion group was 5.2% at one year versus 1.7% in controls but this did not reach statistical significance (HR 1.9; p = 0.33). Compared with controls, there was no significant difference in rate of dislocation in patients without a sacral fusion. When the sacrum was involved, the rate of dislocation was significantly higher than in controls (HR 4.5; p = 0.03), with a trend to more dislocations in longer lumbosacral fusions. Patient demographics and surgical characteristics of THA (i.e. surgical approach and femoral head diameter) did not significantly impact risk of dislocation (p > 0.05). Significant radiological differences were measured in mean anterior pelvic tilt between the one-level lumbar fusion group (22°), the multiple-level fusion group (27°), and the sacral fusion group (32°; p < 0.01). Ten-year survival was 93% in the fusion group and 95% in controls (HR 1.2; p = 0.8). Conclusion Lumbosacral spinal fusions prior to THA increase the risk of dislocation within the first six months. Fusions involving the sacrum with multiple levels of lumbar involvement notably increased the risk of postoperative dislocation compared with a control group and other lumbar fusions. Surgeons should take care with component positioning and may consider higher stability implants in this high-risk cohort.

Background: Periprosthetic joint infection (PJI) of the knee with concurrent disruption of the extensor mechanism is a devastating complication. Historically, knees with such complications have been salvaged with use of an arthrodesis or amputation. The purpose of this study was to assess the survival and functional outcomes of a 2-stage exchange arthroplasty combined with knitted monofilament polypropylene (Marlex; C.R. Bard) mesh reconstruction of the extensor mechanism. Methods: From 2000 to 2015, 16 patients underwent a 2-stage exchange arthroplasty and Marlex-mesh reconstruction for PJI with an extensor mechanism disruption. The study included 9 male patients and 7 female patients with a mean age at the time of reimplantation and mesh reconstruction of 64 years. The mean follow-up was 4 years. PJI was diagnosed on the basis of the Musculoskeletal Infection Society criteria. Clinical outcomes, including survivorship, Knee Society Score (KSS) results, and complications, were assessed. Results: Of 16 reconstructions, 13 were in place at the time of the latest follow-up. At 2 years, survivorship free of mesh failure was 86%, survivorship free of PJI was 87%, and survivorship free of PJI or mesh failure was 75%. The mean KSS improved from 48 prior to resection to 74 after mesh reconstruction and reimplantation. The mean extensor lag improved from 31° prior to resection to 3° after mesh reconstruction. Two patients required mesh revision, 1 patient required an above-the-knee amputation for complex wound complications related to reinfection, 1 patient developed a reinfection requiring irrigation and debridement, and 1 patient developed a superficial infection that required debridement. Conclusions: Two-stage exchange arthroplasty combined with Marlex-mesh reconstruction of the extensor mechanism is a viable alternative to knee arthrodesis or amputation. At 2 years, 75% of mesh reconstructions were in place and without evidence of PJI. Moreover, the functional outcomes were improved, with a negligible extensor lag. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background: Disruption of the extensor mechanism after total knee arthroplasty (TKA) is debilitating, and the reported results of numerous reconstructive options have varied. We previously reported the early results of 13 patients who underwent reconstruction of the extensor mechanism with use of Marlex mesh. The purpose of the current study was to assess results in a larger cohort of patients, with an emphasis on the survivorship of the mesh, clinical results, and complications. Methods: During the period of 2000 to 2015 at a single tertiary care academic institution, 77 patients (77 TKAs) underwent reconstruction with use of Marlex mesh for an extensor mechanism disruption (27 quadriceps tendon disruptions, 40 patellar tendon disruptions, and 10 patellar fractures). The mean patient age at the time of reconstruction was 65 years; 70% of the patients were female. The mean body mass index was 35 kg/m 2 . The mean follow-up was 4 years. Eighteen (23%) of the patients underwent mesh reconstruction with the primary TKA in place, and 59 (77%) had mesh reconstruction at the time of revision TKA. The mean time between disruption and reconstruction was 7 months. Twenty (26%) of the patients had previously undergone attempted extensor mechanism reconstruction at outside institutions. Results: Sixty-five of the 77 mesh reconstructions were in place at the time of the latest follow-up. Twelve patients experienced a failure that required mesh revision: 5 for patellar tendon rupture, 5 for quadriceps tendon rupture, and 2 for symptomatic lengthening. Four additional patients with mesh failure were treated nonoperatively with bracing. The 2-year survivorship free of mesh revision was 86% for patients with no prior reconstruction and 95% for patients with previous reconstructions of the extensor mechanism that did not involve Marlex mesh. Knee Society Score (KSS) results significantly improved following reconstruction (p < 0.001). Extensor lag improved by a mean of 26°, with mean postoperative extensor lag measuring 9° (p < 0.001). Conclusions: Reconstruction of the extensor mechanism with use of Marlex mesh is a viable option in patients with catastrophic disruption after TKA. At the time of the latest follow-up, 84% of the mesh reconstructions were in place and the functional outcomes were excellent, with mean improvement in extensor lag of 26°. Extended follow-up is required, but the results of this large series with a mean follow-up of 4 years are encouraging. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

ABSTRACTTrauma, surgery, and other inflammatory conditions can lead to debilitating joint contractures. Adjunct pharmacologic modalities may permit clinical prevention and treatment of recalcitrant joint contractures. We investigated the therapeutic potential of rosiglitazone by intra‐articular delivery via oligo[poly(ethylene glycol)fumarate] (OPF) hydrogels in an established rabbit model of arthrofibrosis. OPF hydrogels loaded with rosiglitazone were characterized for drug elution properties upon soaking in minimum essential media (MEM) with 10% fetal bovine serum and measurements of drug concentrations via High Performance Liquid Chromatography (HPLC). Drug‐loaded scaffolds were surgically implanted into 24 skeletally mature female New Zealand White rabbits that were divided into equal groups receiving OPF hydrogels loaded with rosiglitazone (1.67 mg), or vehicle control (10 µl DMSO). After 8 weeks of joint immobilization, rabbits were allowed unrestricted cage activity for 16 weeks. Contracture angles of rabbit limbs treated with rosiglitazone showed statistically significant improvements in flexion compared to control animals (mean angles, respectively, 64.4° vs. 53.3°, p < 0.03). At time of sacrifice (week 24), animals in the rosiglitazone group continued to exhibit less joint contracture than controls (119.0° vs. 99.5°, p = 0.014). The intra‐articular delivery of rosiglitazone using implanted OPF hydrogels decreases flexion contractures in a rabbit model of arthrofibrosis without causing adverse effects (e.g., gross inflammation or arthritis). Statement of Clinical Significance: Post‐traumatic joint contractures are common and debilitating, with limited available treatment options. Pharmacologic interventions can potentially prevent and treat such contractures. This study is translational in that a commercially approved medication has been repurposed through a novel delivery device. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2949–2955, 2018.