Browsing by Subject "arthritis"
Results Per Page
Sort Options
Item Open Access An Objective Computational Method to Quantify Ankle Osteoarthritis From Low-Dose Weightbearing Computed Tomography.(Foot & ankle orthopaedics, 2022-07) Tazegul, Tutku E; Anderson, Donald D; Barbachan Mansur, Nacime S; Kajimura Chinelati, Rogerio Marcio; Iehl, Caleb; VandeLune, Christian; Ahrenholz, Samuel; Lalevee, Matthieu; de Cesar Netto, CesarBackground
The treatment of ankle osteoarthritis (OA) varies depending on the severity and distribution of the associated joint degeneration. Disease staging is typically based on subjective grading of appearance on conventional plain radiographs, with reported subpar reproducibility and reliability. The purpose of this study was to develop and describe computational methods to objectively quantify radiographic changes associated with ankle OA apparent on low-dose weightbearing CT (WBCT).Methods
Two patients with ankle OA and 1 healthy control who had all undergone WBCT of the foot and ankle were analyzed. The severity of OA in the ankle of each patient was scored using the Kellgren-Lawrence (KL) classification using plain radiographs. For each ankle, a volume of interest (VOI) was centered on the tibiotalar joint. Initial computation analysis used WBCT image intensity (Hounsfield units [HU]) profiles along lines perpendicular to the subchondral bone/cartilage interface of the distal tibia extending across the entire VOI. Graphical plots of the HU distributions were generated and recorded for each line. These plots were then used to calculate the joint space width (JSW) and HU contrast.Results
The average JSW was 3.89 mm for the control ankle, 3.06 mm for mild arthritis (KL 2), and 1.57 mm for severe arthritis (KL 4). The average HU contrast was 72.31 for control, 62.69 for mild arthritis, and 33.98 for severe arthritis. The use of 4 projections at different locations throughout the joint allowed us to visualize specifically which quadrants have reduced joint space width and contrast.Conclusion
In this technique report, we describe a novel methodology for objective quantitative assessment of OA using JSW and HU contrast.Clinical relevance
Objective, software-based measurements are generally more reliable than subjective qualitative evaluations. This method may offer a starting point for the development of a more robust OA classification system or deeper understanding of the pathogenesis and response to ankle OA treatment.Item Open Access CXCL10 is Upregulated in Synovium and Cartilage following Articular Fracture.(J Orthop Res, 2017-09-14) Furman, Bridgette D; Kent, Collin L; Huebner, Janet L; Kraus, Virginia B; McNulty, Amy L; Guilak, Farshid; Olson, Steven AThe objective of this study was to investigate the expression of the chemokine CXCL10 and its role in joint tissues following articular fracture. We hypothesized that CXCL10 is upregulated following articular fracture and contributes to cartilage degradation associated with post-traumatic arthritis (PTA). To evaluate CXCL10 expression following articular fracture, gene expression was quantified in synovial tissue from knee joints of C57BL/6 mice that develop PTA following articular fracture, and MRL/MpJ mice that are protected from PTA. CXCL10 protein expression was assessed in human cartilage in normal, osteoarthritic (OA), and post-traumatic tissue using immunohistochemistry. The effects of exogenous CXCL10, alone and in combination with IL-1, on porcine cartilage explants were assessed by quantifying the release of catabolic mediators. Synovial tissue gene expression of CXCL10 was upregulated by joint trauma, peaking one day in C57BL/6 mice (25-fold) vs. three days post-fracture in MRL/MpJ mice (15-fold). CXCL10 protein in articular cartilage was most highly expressed following trauma compared with normal and OA tissue. In a dose dependent manner, exogenous CXCL10 significantly reduced total matrix metalloproteinase (MMP) and aggrecanase activity of culture media from cartilage explants. CXCL10 also trended toward a reduction in IL-1α-stimulated total MMP activity (p=0.09) and S-GAG (p=0.09), but not NO release. In conclusion, CXCL10 was upregulated in synovium and chondrocytes following trauma. However, exogenous CXCL10 did not induce a catabolic response in cartilage. CXCL10 may play a role in modulating the chondrocyte response to inflammatory stimuli associated with joint injury and the progression of PTA. This article is protected by copyright. All rights reserved.Item Open Access Initial displacement of the intra-articular surface after articular fracture correlates with PTA in C57BL/6 mice but not "superhealer" MRL/MpJ mice.(Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2021-09) Vovos, Tyler J; Furman, Bridgette D; Huebner, Janet L; Kimmerling, Kelly A; Utturkar, Gangadhar M; Green, Cynthia L; Kraus, Virginia B; Guilak, Farshid; Olson, Steven APosttraumatic arthritis (PTA) occurs commonly after articular fracture and may arise, in part, from joint surface incongruity after injury. MRL/MpJ (MRL) "super-healer" mice are protected from PTA compared to C57BL/6 (B6) mice following articular fracture. However, the relationship between the initial displacement of the articular surface, biologic response, and susceptibility to PTA after fracture remains unclear. The objective of this study was to assess whether joint incongruity after articular fracture, as measured by in vivo micro-computed tomography (microCT), could predict pathomechanisms of PTA in mice. B6 and MRL mice (n = 12/strain) received a closed articular fracture (fx) of the left tibial plateau. Articular incongruity was quantified as bone surface deviations (BSD) for each in vivo microCT scan obtained from pre-fx to 8 weeks post-fx, followed by histologic assessment of arthritis. Serum concentrations of bone formation (PINP) and bone resorption (CTX-I) biomarkers were quantified longitudinally. Both strains showed increases in surface incongruity over time, as measured by increases in BSD. In B6 mice, acute surface incongruity was significantly correlated to the severity of PTA (R 2 = 0.988; p = .0006), but not in MRL mice (R 2 = 0.224; p = .220). PINP concentrations significantly decreased immediately post-fx in B6 mice (p = .023) but not in MRL mice, indicating higher bone synthesis in MRL mice. MRL/MpJ mice demonstrate a unique biologic response to articular fracture such that the observed articular bone surface displacement does not correlate with the severity of subsequent PTA. Clinical Relevance: Identifying therapies to enhance acute biologic repair following articular fracture may mitigate the risk of articular surface displacement for PTA.Item Open Access Mechanisms of immune-related adverse events during the treatment of cancer with immune checkpoint inhibitors.(Rheumatology (Oxford, England), 2019-12) Weinmann, Sophia C; Pisetsky, David SImmune checkpoint inhibitors are novel biologic agents to treat cancer by inhibiting the regulatory interactions that limit T cell cytotoxicity to tumours. Current agents target either CTLA-4 or the PD-1/PD-L1 axis. Because checkpoints may also regulate autoreactivity, immune checkpoint inhibitor therapy is complicated by side effects known as immune-related adverse events (irAEs). The aim of this article is to review the mechanisms of these events. irAEs can involve different tissues and include arthritis and other rheumatic manifestations. The frequency of irAEs is related to the checkpoint inhibited, with the combination of agents more toxic. Because of their severity, irAEs can limit therapy and require immunosuppressive treatment. The mechanisms leading to irAEs are likely similar to those promoting anti-tumour responses and involve expansion of the T cell repertoire; furthermore, immune checkpoint inhibitors can affect B cell responses and induce autoantibody production. Better understanding of the mechanisms of irAEs will be important to improve patient outcome as well as quality of life during treatment.Item Open Access Outcomes After Total Ankle Replacement in Association With Ipsilateral Hindfoot Arthrodesis.(Foot Ankle Int, 2014-06) Lewis, John S; Adams, Samuel B; Queen, Robin M; DeOrio, James K; Nunley, James A; Easley, Mark EBACKGROUND: Ipsilateral hindfoot arthrodesis in combination with total ankle replacement (TAR) may diminish functional outcome and prosthesis survivorship compared to isolated TAR. We compared the outcome of isolated TAR to outcomes of TAR with ipsilateral hindfoot arthrodesis. METHODS: In a consecutive series of 404 primary TARs in 396 patients, 70 patients (17.3%) had a hindfoot fusion before, after, or at the time of TAR; the majority had either an isolated subtalar arthrodesis (n = 43, 62%) or triple arthrodesis (n = 15, 21%). The remaining 334 isolated TARs served as the control group. Mean patient follow-up was 3.2 years (range, 24-72 months). RESULTS: The SF-36 total, AOFAS Hindfoot-Ankle pain subscale, Foot and Ankle Disability Index, and Short Musculoskeletal Function Assessment scores were significantly improved from preoperative measures, with no significant differences between the hindfoot arthrodesis and control groups. The AOFAS Hindfoot-Ankle total, function, and alignment scores were significantly improved for both groups, albeit the control group demonstrated significantly higher scores in all 3 scales. Furthermore, the control group demonstrated a significantly greater improvement in VAS pain score compared to the hindfoot arthrodesis group. Walking speed, sit-to-stand time, and 4-square step test time were significantly improved for both groups at each postoperative time point; however, the hindfoot arthrodesis group completed these tests significantly slower than the control group. There was no significant difference in terms of talar component subsidence between the fusion (2.6 mm) and control groups (2.0 mm). The failure rate in the hindfoot fusion group (10.0%) was significantly higher than that in the control group (2.4%; p < 0.05). CONCLUSION: To our knowledge, this study represents the first series evaluating the clinical outcome of TARs performed with and without hindfoot fusion using implants available in the United States. At follow-up of 3.2 years, TAR performed with ipsilateral hindfoot arthrodesis resulted in significant improvements in pain and functional outcome; in contrast to prior studies, however, overall outcome was inferior to that of isolated TAR. LEVEL OF EVIDENCE: Level II, prospective comparative series.Item Open Access The Role of Collagen VI in the Structure and Properties of the Knee Joint(2009) Henz, SusanKnee pain is a common complaint among older Americans, nearly half of whom have developed or will develop painful osteoarthritis. Osteoarthritis is primarily a disease of articular cartilage, the low-friction, shock-absorbing connective tissue that lines long bones at their articulating surfaces. Within these joint tissues and within arthritis, the minor protein collagen VI plays an uncertain role, although it has been implicated in several muscle and ligament disorders. Determination of the collagen VI role in bone and cartilage of the knee is the focus of this dissertation.
Within articular cartilage, collagen VI exclusively localizes to and delimits the pericellular matrix (PCM), which differs from the extracellular matrix (ECM) in composition and structure. To interact with the cell, a molecule must first pass through the PCM. Fluorescent dextran diffusivities were quantified in the cartilage PCM using a newly developed model of scanning microphotolysis (SCAMP), a line photobleaching technique. Diffusion was slower in the PCM than in the ECM, although not in early-stage arthritic tissue. These results support the hypothesis that diffusivity is lower in the PCM than in the ECM of healthy articular cartilage, presumably due to differences in proteoglycan content.
Arthritic degradation is partly mediated by interleukin-1 (IL-1), a catabolic cytokine that affects the mechanical properties of articular cartilage and preferentially binds to cell-surface receptors in the surface zone. Since cells are the cartilage metabolic units, matrix degradation is hypothesized to influence molecular transport in the PCM before the ECM. Cartilage was cultured with or without IL-1, soaked in FITC-ovalbumin, and photobleached using SCAMP to measure diffusivity. Over 7 days of culture, IL-1 doubled the diffusivity in both zones (surface, middle) and matrices (PCM, ECM) of the cartilage. Diffusivity within the PCM was slightly lower than within the ECM. No increase in PCM diffusivity relative to ECM diffusivity was detected within either zone, suggesting that PCM-localized degradation either cannot be distinguished at these time points or cannot be detected by measures of ovalbumin diffusion.
To determine the effects of collagen VI absence on the morphometry and physical properties of the joint, knees of 2-, 9-, and 15-month-old Col6a1+/+ and Col6a1-/- mice were studied. Bone morphometry was evaluated using micro-computed tomography (microCT). Subchondral bone thickness, joint-capsule thickness, and cartilage degradation were assessed by histology. Cartilage elastic modulus, roughness, and coefficient of friction were measured by atomic force microscopy (AFM). Diffusion through the cartilage ECM was determined by SCAMP. Overall, collagen VI absence had profound effects on the morphometry of the proximal tibia and the overall histological structures of the mouse knee, yet minimal effects on the friction, roughness, elastic modulus, and diffusional properties of the articular cartilage. Musculoskeletal abnormalities at the knee do result from collagen VI absence.