Mikayel Grigoryan

Quadriceps strength and the risk of cartilage loss and symptom progression in knee osteoarthritis

OBJECTIVE To determine the effect of quadriceps strength in individuals with knee osteoarthritis (OA) on loss of cartilage at the tibiofemoral and patellofemoral joints (assessed by magnetic resonance imaging [MRI]) and on knee pain and function. METHODS We studied 265 subjects (154 men and 111 women, mean+/-SD age 67+/-9 years) who met the American College of Rheumatology criteria for symptomatic knee OA and who were participating in a prospective, 30-month natural history study of knee OA. Quadriceps strength was measured at baseline, isokinetically, during concentric knee extension. MRI of the knee at baseline and at 15 and 30 months was used to assess cartilage loss at the tibiofemoral and patellofemoral joints, with medial and lateral compartments assessed separately. At baseline and at followup visits, knee pain was assessed using a visual analog scale, and physical function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index. RESULTS There was no association between quadriceps strength and cartilage loss at the tibiofemoral joint. Results were similar in malaligned knees. However, greater quadriceps strength was protective against cartilage loss at the lateral compartment of the patellofemoral joint (for highest versus lowest tertile of strength, odds ratio 0.4 [95% confidence interval 0.2, 0.9]). Those with greater quadriceps strength had less knee pain and better physical function over followup (P<0.001). CONCLUSION Greater quadriceps strength had no influence on cartilage loss at the tibiofemoral joint, including in malaligned knees. We report for the first time that greater quadriceps strength protected against cartilage loss at the lateral compartment of the patellofemoral joint, a finding that requires confirmation. Subjects with greater quadriceps strength also had less knee pain and better physical function over followup.

Complete Anterior Cruciate Ligament Tear and the Risk for Cartilage Loss and Progression of Symptoms in Men and Women with Knee Osteoarthritis

OBJECTIVE To determine whether a complete anterior cruciate ligament (ACL) tear, a frequent incidental finding on magnetic resonance imagings (MRIs) of individuals with established knee osteoarthritis (OA), increases the risk for further knee OA progression. METHODS We examined 265 participants (43% women) with symptomatic knee OA in a 30-month, prospective, natural history study of knee OA. The more symptomatic knee was imaged using MRI at baseline, 15 and 30 months. Cartilage was scored at the medial and lateral tibiofemoral joint and at the patellofemoral joint using the Whole-Organ MRI Score (WORMS) semi-quantitative method. Complete ACL tear was determined on baseline MRI. At each visit, knee pain was assessed using a knee-specific visual analog scale and physical function was assessed using the Western Ontario and McMaster Universities (WOMAC) physical function subscale. RESULTS There were 49 participants (19%) with complete ACL tear at baseline. Adjusting for age, body mass index, gender and baseline cartilage scores, complete ACL tear increased the risk for cartilage loss at the medial tibiofemoral compartment [odds ratio (OR): 1.8, 95% confidence interval (CI): 1.1, 3.2]. However, following adjustment for the presence of medial meniscal tears, no increased risk for cartilage loss was further seen (OR: 1.1, 95% CI: 0.6, 1.8). Knee pain and physical function were similar over follow-up between those with and without a complete ACL tear. CONCLUSIONS Individuals with knee OA and incidental complete ACL tear have an increased risk for cartilage loss that appears to be mediated by concurrent meniscal pathology. The presence of a complete ACL tear did not influence the level of knee pain or physical function over short-term follow-up.

Quantitative and qualitative assessment of closed fracture healing using computed tomography and conventional radiography1

Abstract Rationale and Objectives. Development of new agents to induce fracture healing requires more sensitive methods to detect early changes in fracture repair. The aims of this study were to determine quantitative and qualitative features of fracture healing using volumetric computed tomography (CT) and to compare them with conventional radiography during the weeks following uncomplicated fractures of the appendicular skeleton. Materials and Methods. 39 otherwise healthy men and women with acute, closed fractures of the distal radius, tibial and/or fibular malleoli, or tibial shaft, were enrolled and underwent CT and X-ray imaging at 1, 2, 4, 8, 12, and 16 (tibial shaft only) weeks post fracture. Qualitative assessment included fracture line/margins, fracture gap, external callus appearance, callus-to-cortex ratio, bridging, and radiologic union. Quantitative assessment of CT density changes (Hounsfield units [HU]) in the fracture gap was performed in a subset of 8 fracture patients using MEDx multimodality image analysis software (Sterling,VA). The analysis was performed by drawing freeform regions of interest (ROI) covering the fracture gap on baseline (week 1) images and by automated registration of the follow-up images to the baseline co-ordinate system. Results. The mean time to achieve radiologic union on CT was slightly shorter than on X-rays for radial and tibial shaft fractures (7.3 vs. 8.0 weeks, P = .1). Blurring of the fracture margins and reactive sclerosis were the earliest signs of healing in both modalities. External callus formation was evident in 11 cases and was detected earlier with CT technique. Overall, CT images allowed for more complete and detailed visualization of healing compared with conventional X-rays, which were limited by cast and fixation hardware superimposition, especially in subjects with malleolar and distal radial fractures. Quantitative evaluation showed good intraobserver and interobserver reproducibility and a statistically significant correlation to qualitative changes. Conclusion. Our methods of fracture healing assessment are reliable tools that are able to detect early changes in normal bone healing and may serve as useful additions to subjective image analysis in monitoring fracture healing in clinical trials. CT shows some advantages over conventional X-rays in evaluation of early fracture healing.

Measurement of changes in trabecular bone at fracture sites using X-ray CT and automated image registration and processing

Currently, there are no in vivo techniques for quantifying healing within fractures involving mainly trabecular bone. Methods for quantitatively assessing healing would aid the investigation of new treatment regimes, and might also be useful for predicting whether a patient may be undergoing delayed union. Using CT and automated image registration, we have developed an image processing technique for measuring changes in CT image intensity at fracture sites. The technique focuses on quantifying the formation of new mineralised tissue within fracture gaps, while ignoring loss of bone mineral due to disuse osteoporosis. Seven patients with fractures of the distal radius were examined for 12 weeks following fracture. To assess reproducibility of measurements of change in CT intensity at the fracture line, measurements were performed on two separate occasions, by each of two independent readers. Reproducibility was compared to rates of change over time, to determine detectable differences in individual progression. Scans were scored qualitatively for features of healing and scores compared to the quantitative measurements. The mean (SD) change in CT intensity was + 128 (65) Hounsfield Units (HU) over the 12 week follow‐up. Inter‐ and intra‐observer reproducibilities were both similar (±17 HU), 1/7 of the change seen during the study. In this small patient cohort, a significant increase in CT intensity was seen 2 weeks post‐fracture. Large early increases in CT intensity were associated with early visual appearance of sclerosis and blurring of the fracture line. In this preliminary, prospective study, we have developed a reproducible quantitative technique for measuring changes in CT intensity of trabecular bone at the fracture line in the distal radius. Further work is required to determine whether it can be used to identify, or monitor patients who are undergoing delayed fracture repair. The technique appears sensitive for measuring changes immediately post‐fracture, and could have a role in examining potential effects of new therapies in patient cohorts.

Cerebral Arteriolar Thromboembolism in Idiopathic Hypereosinophilic Syndrome

OBJECTIVE To describe imaging findings as well as postmortem brain and cardiac pathology in a patient with fulminant idiopathic hypereosinophilic syndrome. DESIGN Case report. SETTING University hospital. PATIENT A 48-year-old right-handed man with hypereosinophilia, rapidly progressive encephalopathy, and focal neurological deficits who died 22 days after presentation. MAIN OUTCOME MEASURES Physical examination, radiologic, and neuropathologic examination results. RESULTS Imaging of the brain revealed bihemispheric ischemic changes in and beyond the watershed distributions. Pathology review demonstrated mural cardiac thrombus that likely caused cardioembolism as well as diffuse microangiopathy despite resolution of the hypereosinophilia. CONCLUSIONS Timely recognition of idiopathic hypereosinophilic syndrome may enable aggressive treatment prior to widespread cardioembolism and degranulation that result in devastating cerebrovascular complications.

Unusually diffuse idiopathic calcinosis cutis

Calcifications in idiopathic calcinosis cutis are most commonly localized to one area. We herein report a 66-year-old woman with idiopathic calcinosis cutis who unusually exhibited widespread calcific deposits. In this report, we will also briefly discuss the pathogenesis, differential diagnosis, and current treatment of this disease.