Tibbo, Meagan E.

(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.

AbstractBackgroundNonuterine leiomyosarcomas (LMS) are common extremity soft‐tissue sarcomas. Deep LMS are at an increased risk for recurrence; however, few studies have focused on superficial LMS.MethodsWe reviewed the clinicopathological features of 82 patients with a primary superficial LMS. The mean age and follow‐up were 57 ± 15 and 7 ± 5 years. Depth was classified as dermal (based in the skin; n = 35, 43%) and subcutaneous (based below the dermis, above the fascia; n = 47, 57%) on the final resection specimen. Dermal cases were treated with negative margin resection, while subcutaneous tumors were evaluated by a multidisciplinary team for consideration of possible adjuvant therapy.ResultsThe 10‐year disease‐specific survival (DSS) for superficial LMS was 90% with no difference (p = .18) in the 10‐year DSS between patients with dermal (100%) and subcutaneous (86%) LMS. All disease recurrences occurred in subcutaneous LMS (17% vs. 0%, p = .02) and subcutaneous tumors had a worse10‐year metastatic free survival (81% vs. 100%, p = .03).ConclusionsThe results of this study suggest that dermal LMS can be managed with a negative margin resection alone. Although the prognosis for patients with subcutaneous LMS is quite favorable, there is some risk for local and distant recurrence, and such patients will benefit from multidisciplinary care.

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.

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.

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.

Background: Suprascapular nerve (SSN) block using bone reference points (BARO) is a technique that in principle is accessible to practitioners without experience in locoregional anesthesia or ultrasound guidance. The primary objective was to validate the feasibility of SSN BARO by an orthopedic surgeon. The secondary objective was to provide a description of the path of the sensory branches from the SSN to the shoulder. Methods: A BARO was performed on 15 cadaveric shoulders by an intern in orthopedic surgery. Ten ml of methylene blue and 0.75% ropivocaine were injected around the SSN. 2.5ml of a red latex solution were also injected to identify the injection site. The distribution of the sensory branches of the NSS was also described. Results: The average distance between the SSN and the injection site was 1.5cm (0-4.5cm). The most frequent injection site was the proximal third of the scapular neck. Fifteen SSNs were marked upstream of the origin of the sensory branches. The 15 SSN produced 3 sensory branches that innervate the posterior glenohumeral capsule, the subacromial bursa, and the coracoclavicular and acromioclavicular ligaments. Conclusion: SSN BARO by an orthopedic surgeon is a simple, reliable, and accurate technique. Injection near the suprascapular notch is recommended to mark the SSN upstream of its three sensory branches.

Abstract Based on the currently available literature, total denervation of the elbow joint is considered impossible. However, consensus with respect to the anatomic location of sensory branches is lacking. The aim of this literature review was to establish consensus with respect to the anatomic features of the articular branches innervating the elbow joint, as well as the distribution of sensory receptors about its capsule. Four electronic databases were queried, between January 1945 and June 2019. Twenty‐one original articles providing a detailed description of the distribution of sensory receptors about the elbow joint capsule (5) and its articular branches (16) were reviewed. The posterior capsule was found to be primarily innervated by the ulnar and radial nerves via combined articular branches and sensory branches of the medial antebrachial cutaneous nerve. The anterior capsule was found to be primarily innervated by a plexus of articular ramifications from muscular branches of mixed nerves (ulnar, musculocutaneous, radial, and median nerves). A higher density of nociceptors and mechano‐receptors was identified within the posterior and anterior capsules, respectively. Thorough denervation, via the technique proposed herein, is likely to be sufficient in eliminating pain from degenerative conditions of the elbow joint.

Background: Distal femoral replacement (DFR) is a salvage option for complex primary and revision total knee arthroplasty (TKA). Although excellent immediate fixation and weight-bearing are achieved, there is a paucity of data on long-term outcomes of TKA with DFR. The purpose of the present study was to determine implant survivorship, clinical outcomes, and radiographic results of TKAs with contemporary DFR components in a large series. Methods: We identified 144 consecutive TKAs performed with DFR for non-oncologic indications from 2000 to 2015 at a single academic institution. Indications for the index DFR included 66 (46%) for native (n = 11) or periprosthetic (n = 55) femoral fracture, 40 (28%) for staged treatment of periprosthetic joint infection, 28 (19%) for aseptic TKA loosening, and 10 (7%) for other indications. Porous metal cones were used to augment femoral fixation in 28 patients (19%) and tibial fixation in 38 patients (26%). Outcomes included cumulative incidence of revision and reoperation (utilizing a competing risk model), Knee Society scores, and radiographic results. The mean age at the time of index DFR was 72 years, and 65% of patients were female. The mean follow-up was 5 years (range, 2 to 13 years) for the 111 patients who did not undergo revision, had not died, and were not lost to follow-up. Results: The 10-year cumulative incidences of revision for aseptic loosening, all-cause revision, and any reoperation were 17.0%, 27.5%, and 46.3%, respectively. There was an increased risk of reoperation in patients who underwent index DFR for aseptic TKA loosening (hazard ratio [HR], 2.30; p = 0.026) or periprosthetic joint infection (HR, 2.18; p = 0.022) compared with periprosthetic or native femoral fractures. However, there was no difference in risk of revision for aseptic loosening or all-cause revision based on the original operative indication. The mean Knee Society score increased from 45 preoperatively to 71 at the time of the latest follow-up (p < 0.001). Radiographic loosening was observed in 8 unrevised DFRs (7%). There were 7 above-the-knee amputations performed at the time of the final follow-up, all for intractable periprosthetic joint infection. Conclusions: TKAs with contemporary DFR had high 10-year cumulative incidences of both revision and reoperation, underscoring the salvage nature of this procedure as a final reconstructive option. Most patients experienced substantial clinical improvements with this end-stage revision procedure. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Update This article was updated on December 6, 2019, because of a previous error. On page 1936, in Table VII, “Performance of the Bearing Surface Algorithm,” the row that had read “Bearing surface predicted by algorithm” now reads “Bearing surface predicted by algorithm*.” An erratum has been published: J Bone Joint Surg Am. 2020 Jan 2;102(1):e4. Update This article was updated on March 31, 2020, because of a previous error. On page 1934, in Table IV (“THA Bearing Surface-Related Keywords in Operative Notes”), the row that had read “Femoral stem; stem; HFx-stem; femoral component; femoral component/stem; permanent prosthesis; stem fem cemented” now reads “Femoral head; ball; delta head; delta ceramic head; ion treated; BIOLOX delta; ceramic head; ceramic femoral head; ceramic offset head; ceramic (size) head; alumina ceramic head; alumina prosthetic head; alumna ceramic head; BIOLOX ceramic head; BIOLOX delta head; BIOLOX femoral head; BIOLOX delta ceramic head.” An erratum has been published: J Bone Joint Surg Am. 2020 May 6;102(9):e43. Background: Manual chart review is labor-intensive and requires specialized knowledge possessed by highly trained medical professionals. Natural language processing (NLP) tools are distinctive in their ability to extract critical information from raw text in electronic health records (EHRs). As a proof of concept for the potential application of this technology, we examined the ability of NLP to correctly identify common elements described by surgeons in operative notes for total hip arthroplasty (THA). Methods: We evaluated primary THAs that had been performed at a single academic institution from 2000 to 2015. A training sample of operative reports was randomly selected to develop prototype NLP algorithms, and additional operative reports were randomly selected as the test sample. Three separate algorithms were created with rules aimed at capturing (1) the operative approach, (2) the fixation method, and (3) the bearing surface category. The algorithms were applied to operative notes to evaluate the language used by 29 different surgeons at our center and were applied to EHR data from outside facilities to determine external validity. Accuracy statistics were calculated with use of manual chart review as the gold standard. Results: The operative approach algorithm demonstrated an accuracy of 99.2% (95% confidence interval [CI], 97.1% to 99.9%). The fixation technique algorithm demonstrated an accuracy of 90.7% (95% CI, 86.8% to 93.8%). The bearing surface algorithm demonstrated an accuracy of 95.8% (95% CI, 92.7% to 97.8%). Additionally, the NLP algorithms applied to operative reports from other institutions yielded comparable performance, demonstrating external validity. Conclusions: NLP-enabled algorithms are a promising alternative to the current gold standard of manual chart review for identifying common data elements from orthopaedic operative notes. The present study provides a proof of concept for use of NLP techniques in clinical research studies and registry-development endeavors to reliably extract data of interest in an expeditious and cost-effective manner.