To develop a model of early osteoarthritis, by examining whether radiographically normal knees with contralateral joint space narrowing (JSN), but without contralateral trauma history, display ...greater longitudinal cartilage composition change (transverse relaxation time; T2) than subjects with bilaterally normal knees.
120 radiographically normal knees (Kellgren Lawrence grade KLG 0) from the Osteoarthritis Initiative were studied. 60 case knees displayed definite contralateral radiographic knee osteoarthritis (KLG ≥ 2) whereas 60 reference subjects were bilaterally KLG0, and were matched 1:1 to cases based on age, sex, and BMI. All had multi-echo spin-echo MRI acquired at year (Y) 1 and 4 follow-up, with cartilage T2 being determined in superficial and deep cartilage layers across 16 femorotibial subregions. T2 across all regions was considered the primary analytic focus.
Of 60 KLG0 case knees (30 female, age: 65.0 ± 8.8 y, BMI: 27.6 ± 4.4 kg/m2), 21/22/13/4 displayed contralateral JSN 0/1/2/3, respectively. The longitudinal increase in the deep layer cartilage T2 between Y1 and Y4 was significantly greater (P = 0.03; Cohen's D 0.50) in the 39 KLG0 case knees with contralateral JSN (1.2 ms; 95% confidence interval CI 0.4, 2.0) than in matched KLG0 reference knees (0.1 ms; 95% CI −0.5, 0.7). No significant differences were identified in superficial T2 change. T2 at Y1 was significantly greater in case than in reference knees, particularly in the superficial layer of the medial compartment.
Radiographically normal knees with contralateral, non-traumatic JSN represent an applicable model of early osteoarthritis, with deep layer cartilage composition (T2) changing more rapidly than in bilaterally normal knees.
NCT00080171.
To investigate the test–retest precision and to report the longitudinal change in cartilage thickness, the percentage of knees with progression and the predictive value of the ...machine-learning-estimated structural progression score (s-score) for cartilage thickness loss in the IMI-APPROACH cohort – an exploratory, 5-center, 2-year prospective follow-up cohort.
Quantitative cartilage morphology at baseline and at least one follow-up visit was available for 270 of the 297 IMI-APPROACH participants (78% females, age: 66.4 ± 7.1 years, body mass index (BMI): 28.1 ± 5.3 kg/m2, 55% with radiographic knee osteoarthritis (OA)) from 1.5T or 3T MRI. Test–retest precision (root mean square coefficient of variation) was assessed from 34 participants. To define progressor knees, smallest detectable change (SDC) thresholds were computed from 11 participants with longitudinal test–retest scans. Binary logistic regression was used to evaluate the odds of progression in femorotibial cartilage thickness (threshold: −211 μm) for the quartile with the highest vs the quartile with the lowest s-scores.
The test–retest precision was 69 μm for the entire femorotibial joint. Over 24 months, mean cartilage thickness loss in the entire femorotibial joint reached −174 μm (95% CI: −207, −141 μm, 32.7% with progression). The s-score was not associated with 24-month progression rates by MRI (OR: 1.30, 95% CI: 0.52, 3.28).
IMI-APPROACH successfully enrolled participants with substantial cartilage thickness loss, although the machine-learning-estimated s-score was not observed to be predictive of cartilage thickness loss. IMI-APPROACH data will be used in subsequent analyses to evaluate the impact of clinical, imaging, biomechanical and biochemical biomarkers on cartilage thickness loss and to refine the machine-learning-based s-score.
NCT03883568.
Evaluate associations between 2-year change in radiographic or quantitative magnetic resonance imaging (qMRI) structural measures, and knee replacement (KR), within a subsequent 7-year follow-up ...period.
Participants from the Osteoarthritis Initiative were selected based on potential eligibility criteria for a disease-modifying osteoarthritis (OA) drug trial: Kellgren–Lawrence grade 2 or 3; medial minimum joint space width (mJSW) ≥2.5 mm; knee pain at worst 4–9 in the past 30 days on an 11-point scale, or 0–3 if medication was taken for joint pain; and availability of structural measures over 2 years. Mean 2-year change in structural measures was estimated and compared with two-sample independent t-tests for KR and no KR. Area under the receiver operating characteristic curve (AUC) was estimated using 2-year change in structural measures for prediction of future KR outcomes.
Among 627 participants, 107 knees underwent KR during a median follow-up of 6.7 years after the 2-year imaging period. Knees that received KR during follow-up had a greater mean loss of cartilage thickness in the total femorotibial joint and medial femorotibial compartment on qMRI, as well as decline in medial fixed joint space width on radiographs, compared with knees that did not receive KR. These imaging measures had similar, although modest discrimination for future KR (AUC 0.62, 0.60, and 0.61, respectively).
2-year changes in qMRI femorotibial cartilage thickness and radiographic JSW measures had similar ability to discriminate future KR in participants with knee OA, suggesting that these measures are comparable biomarkers/surrogate endpoints of structural progression.
Summary Objective Fast low angle shot (FLASH) and double echo steady state (DESS) magnetic resonance imaging (MRI) acquisitions were recently cross-calibrated for quantification of cartilage ...morphology at 3 T. In this pilot study for the osteoarthritis (OA) initiative we compare their test–retest-precision and sensitivity to longitudinal change. Method Nine participants with mild to moderate clinical OA were imaged twice each at baseline, year 1 (Y1) and year 2 (Y2). Coronal 1.5 mm FLASH and sagittal 0.7 mm DESS sequences were acquired; 1.5 mm coronal multiplanar reformats (MPR) were obtained from the DESS. Patellar, femoral and tibial cartilage plates were quantified in a paired fashion, with blinding to time point. Results In the weight-bearing femorotibial joint, average precision errors across plates were 1.8% for FLASH, 2.6% for DESS, and 3.0% for MPR-DESS. Volume loss at Y1 was not significant; at Y2 the average change across the femorotibial cartilage plates was −1.7% for FLASH, −2.8% for DESS, and −0.3% for MPR-DESS. Volume change in the lateral tibia (−5.5%; P < 0.03), and in the medial (−2.9%; P < 0.04) and lateral femorotibial compartments (−3.8%; P < 0.03) were significant for DESS. Conclusions FLASH, DESS and MPR-DESS all displayed adequate test–retest precision. Although the comparison between protocols is limited by the small number of participants and by the relatively small longitudinal change in cartilage morphology in this pilot study, the data suggest that significant change can be detected with MRI in a small sample of OA subjects over 2 years.
Objectives
The aim of the current study was to evaluate potential differences in the accuracy of mandibular reconstruction and long-term stability, with respect to different reconstructive ...procedures.
Methods
In total, 42 patients who had undergone primary segmental mandibular resection with immediate alloplastic reconstruction, with either manually pre-bent or patient-specific mandibular reconstruction plates (PSMRP), were included in this study. Mandibular dimensions, in terms of six clinically relevant distances (capitulum most lateral points, capitulum most medial points, incisura most caudal points, mandibular foramina, coronoid process most cranial points, dorsal tip of the mandible closest to the gonion point) determined from tomographic images, were compared prior to, and after surgery.
Results
Dimensional alterations were significantly more often found when conventionally bent titanium reconstruction plates were used. These occurred in the area of the coronoid process (
p
= 0.014). Plate fractures were significantly (
p
= 0.022) more often found within the manually pre-bent group than within the PSMRP group (17%/0%).
Conclusion
The results suggest that the use of PSMRP may prevent rotation of the proximal mandibular segment, thus avoiding functional impairment. In addition, the use of PSMRP may potentially enhance the long-term stability of alloplastic reconstructions.
In patients undergoing bariatric surgery or medical management for obesity, we assessed whether those experiencing substantial weight loss had changes in innervated knee structures or in cartilage.
...Severely obese patients (body mass index (BMI) ≥35) with knee pain on most days were seen before bariatric surgery or medical weight management and at 1-year follow-up. Examinations included 3T MRI acquired at both time points for semi-quantitative scoring of bone marrow lesions (BML), synovitis, cartilage damage, and for quantitative measurement of cartilage thickness. Association of ≥20% vs <20% weight loss with change in semi-quantitative scores was evaluated using linear mixed-effects models, and that with cartilage thickness change used non-parametric and parametric methods. Sensitivity analyses tested different thresholds for weight loss, weight loss as a continuous measure, examined those with and without bariatric surgery, and with worse osteoarthritis (OA).
75 subjects (median age 49 years, 92% women) were included. At baseline, 61 subjects (81%) had Kellgren and Lawrence (KL) grade >0, and 16 (21%) had KL grade ≥3; 69 (92%) had cartilage damage. For BML, synovitis, and cartilage damage, the majority of knees had change in semi-quantitative scores of 0, and there was no difference between those with and without ≥20% weight loss. Similarly, in terms of cartilage thickness loss, in 14 of 16 sub-regions thickness loss was not associated with weight loss. Sensitivity analyses showed similar findings.
In middle-aged persons with mostly mild radiographic OA, structural features changed little over a year and weight loss was not associated with effects on structural changes.
There is significant variability in the trajectory of structural progression across people with knee osteoarthritis (OA). We aimed to identify distinct trajectories of femorotibial cartilage ...thickness over 2 years and develop a prediction model to identify individuals experiencing progressive cartilage loss.
We analysed data from the Osteoarthritis Initiative (OAI) (n = 1,014). Latent class growth analysis (LCGA) was used to identify trajectories of medial femorotibial cartilage thickness assessed on magnetic resonance imaging (MRI) at baseline, 1 and 2 years. Baseline characteristics were compared between trajectory-based subgroups and a prediction model was developed including those with frequent knee symptoms at baseline (n = 686). To examine clinical relevance of the trajectories, we assessed their association with concurrent changes in knee pain and incidence of total knee replacement (TKR) over 4 years.
The optimal model identified three distinct trajectories: (1) stable (87.7% of the population, mean change −0.08 mm, SD 0.19); (2) moderate cartilage loss (10.0%, −0.75 mm, SD 0.16) and (3) substantial cartilage loss (2.2%, −1.38 mm, SD 0.23). Higher Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) pain scores, family history of TKR, obesity, radiographic medial joint space narrowing (JSN) ≥1 and pain duration ≤1 year were predictive of belonging to either the moderate or substantial cartilage loss trajectory area under the curve (AUC) 0.79, 95% confidence interval (CI) 0.74, 0.84. The two progression trajectories combined were associated with pain progression (OR 1.99, 95% CI 1.34, 2.97) and incidence of TKR (OR 4.34, 1.62, 11.62).
A minority of individuals follow a progressive cartilage loss trajectory which was strongly associated with poorer clinical outcomes. If externally validated, the prediction model may help to select individuals who may benefit from cartilage-targeted therapies.
Objective Sutureless valves are designed to facilitate surgical implantation, including less-invasive techniques in aortic valve replacement, by maintaining surgical precision of implantation ...compared with transcatheter techniques. Long-term clinical experience with sutureless valves is lacking. We report the 5-year follow-up results of an international, prospective, multicenter study evaluating the clinical performance and safety of the 3f Enable valve (Medtronic Inc, Minneapolis, Minn). Methods Between March 2007 and December 2009, 141 patients (54 male; mean age, 76.1 ± 5.7 years) undergoing aortic valve replacement with the 3f Enable valve were enrolled in 10 European sites. The mean follow-up was 2.76 years (range, 2 days to 5.1 years; total, 388.7 patient-years). Echocardiographic valvular hemodynamic and morphologic analyses were performed by an independent core laboratory. Results The mean systolic gradient was 10.4 ± 4.4 mm Hg at discharge and 7.7 ± 4.1 mm Hg at 5 years. The mean effective orifice area was 1.7 ± 0.5 cm2 at discharge and 1.6 ± 0.2 cm2 at 5 years. Freedom from all-cause and valve-related mortality was 87.6% ± 2.9% and 96.8% ± 1.6% at 1 year (113 patients at risk) and 77.0% ± 7.5% and 93.8% ± 4.8% at 5 years (24 patients at risk), respectively. Six patients underwent reoperation (4 because of major paravalvular leakage and 2 because of endocarditis). Freedom from reoperation was 95.4% ± 1.9% at 1 year and 95.4% ± 6.1% at 5 years. No structural valve deterioration occurred during the follow-up period. Conclusions The sutureless 3f Enable valve represents a safe and effective treatment for aortic valve stenosis, providing an excellent hemodynamic profile. This study represents the longest follow-up study for a sutureless bioprosthesis. Sutureless valves may become an option for all patients with indicated biological aortic valve replacement.
Quantitative information about bone tissue‐level loading is essential for understanding bone mechanical behavior. We made microfinite element models of a healthy and osteoporotic human femur and ...found that tissue‐level strains in the osteoporotic femoral head were 70% higher on average and less uniformly distributed than those in the healthy one.
Introduction: Bone tissue stresses and strains in healthy load‐adapted trabecular architectures should be distributed rather evenly, because no bone tissue is expected to be overloaded or unused. In this study, we evaluate this paradigm with the use of microfinite element (μFE) analyses to calculate tissue‐level stresses and strains for the human femur. Our objectives were to quantify the strain distribution in the healthy femur, to investigate to what extent this distribution is affected by osteoporosis, to determine if osteoporotic bone is simply bone adapted to lower load levels, and to determine the “safety factor” for trabecular bone.
Materials and Methods: μFE models of a healthy and osteoporotic proximal femur were made from microcomputed tomography images. The models consisted of over 96 and 71 million elements for the healthy and osteoporotic femur, respectively, and represented their internal and external morphology in detail. Stresses and strains were calculated for each element and their distributions were calculated for a volume of interest (VOI) of trabecular bone in the femoral head.
Results: The average tissue‐level principal strain magnitude in the healthy VOI was 304 ± 185 microstrains and that in the osteoporotic VOI was 520 ± 355 microstrains. Calculated safety factors were 8.6 for the healthy and 4.9 for the osteoporotic femurs. After reducing the force applied to the osteoporotic model to 59%, the average strain compared with that of the healthy femur, but the SD was larger (208 microstrains).
Conclusions: Strain magnitudes in the osteoporotic bone were much higher and less uniformly distributed than those in the healthy one. After simulated joint‐load reduction, strain magnitudes in the osteoporotic femur were very similar to those in the healthy one, but their distribution is still wider and thus less favorable.
Magnetic resonance imaging (MRI)-based spin-spin relaxation time (T2) mapping has been shown to be associated with cartilage matrix composition (hydration, collagen content &orientation). To ...determine the impact of early radiographic knee osteoarthritis (ROA) and ROA risk factors on femorotibial cartilage composition, we studied baseline values and one-year change in superficial and deep cartilage T2 layers in 60 subjects (age 60.6 ± 9.6 y; BMI 27.8 ± 4.8) with definite osteophytes in one knee (earlyROA, n = 32) and with ROA risk factors in the contralateral knee (riskROA, n = 28), and 89 healthy subjects (age 55.0 ± 7.5 y; BMI 24.4 ± 3.1) without signs or risk factors of ROA. Baseline T2 did not differ significantly between earlyROA and riskROA knees in the superficial (48.0 ± 3.5 ms vs. 48.1 ± 3.1 ms) or the deep layer (37.3 ± 2.5 ms vs. 37.3 ± 1.8 ms). However, healthy knees showed significantly lower superficial layer T2 (45.4 ± 2.3 ms) than earlyROA or riskROA knees (p ≤ 0.001) and significantly lower deep layer T2 (35.8 ± 1.8 ms) than riskROA knees (p = 0.006). Significant longitudinal change in T2 (superficial: 0.5 ± 1.4 ms; deep: 0.8 ± 1.3 ms) was only detected in healthy knees. These results do not suggest an association of early ROA (osteophytes) with cartilage composition, as assessed by T2 mapping, whereas cartilage composition was observed to differ between knees with and without ROA risk factors.
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