Exercise-induced pain changes associate with changes in muscle perfusion in knee osteoarthritis: exploratory outcome analyses of a randomised controlled trial.

BACKGROUND: Exercise therapy is recommended for knee osteoarthritis (OA), but the underlying mechanisms of pain relief are not fully understood. The purpose of this study was to explore the effects of exercise on muscle perfusion assessed by dynamic contrast enhanced MRI (DCE-MRI) and its association with changes in pain in patients with knee OA. METHODS: Exploratory outcome analyses of a randomised controlled study with per-protocol analyses ( ClinicalTrials.gov : NCT01545258) performed at an outpatient clinic at a public hospital in Denmark. We compared 12 weeks of supervised exercise therapy 3 times per week (ET) with a no attention control group (CG). Analyses of covariance (ANCOVA) were used to assess group mean differences in changes from baseline to week 12 in knee muscle perfusion quantified by DCE-MRI, patient-reported pain and function using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, knee extensor and flexor muscle strength tests, and the six-minute walking test (6MWT). Spearman's correlation coefficients were used to determine the correlation between changes in DCE-MRI variables, KOOS, muscle strength, and 6MWT. The potential effect mediation of the DCE-MRI perfusion variables was investigated in a post-hoc mediation analysis. RESULTS: Of 60 participants randomised with knee osteoarthritis, 33 (ET, n = 16, CG, n = 17) adhered to the protocol and had complete DCE-MRI data. At follow-up, there were significant group differences in muscle perfusion changes and clinically relevant group differences in KOOS pain changes (10.7, 95% CI 3.3 to 18.1, P = 0.006) in favor of ET. There were no significant between-group differences on muscle strength and function. The changes in pain and muscle perfusion were significantly correlated (highest Spearman's rho = 0.42, P = 0.014). The mediation analyses were generally not statistically significant. CONCLUSION: The pain-reducing effects of a 12-week exercise program are associated with changes in knee muscle perfusion quantified by DCE-MRI in individuals with knee OA, but whether the effects are mediated by muscle perfusion changes remains unclear. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01545258 , first posted March 6, 2012.

Randomized Trial of Surgical Left Atrial Appendage Closure: Protection Against Cerebrovascular Events.

Following open-heart surgery, atrial fibrillation and stroke occur frequently. Left atrial appendage closure added to elective open-heart surgery could reduce the risk of ischemic stroke. We aim to examine if routine closure of the left atrial appendage in patients undergoing open-heart surgery provides long-term protection against cerebrovascular events independently of atrial fibrillation history, stroke risk, and oral anticoagulation use. Long-term follow-up of patients enrolled in the prospective, randomized, open-label, blinded evaluation trial entitled left atrial appendage closure by surgery (NCT02378116). Patients were stratified by oral anticoagulation status and randomized (1:1) to left atrial appendage closure in addition to elective open-heart surgery vs standard care. The primary composite endpoint was ischemic stroke events, transient ischemic attacks, and imaging findings of silent cerebral ischemic lesions. Two neurologists blinded for treatment assignment adjudicated cerebrovascular events. In total, 186 patients (82% males) were reviewed. At baseline, mean (standard deviation (SD)) age was68 (9) years and 13.4% (n = 25/186) had been diagnosed with atrial fibrillation. Median [interquartile range (IQR)] CHA2DS2-VASc was 3 [2,4] and 25.9% (n = 48/186) were receiving oral anticoagulants. Mean follow-up was 6.2 (2.5) years. The left atrial appendage closure group experienced fewer cerebrovascular events; intention-to-treat 11 vs 19 (P = 0.033, n = 186) and per-protocol 9 vs 17 (P = 0.186, n = 141). Left atrial appendage closure as an add-on open-heart surgery, regardless of pre-surgery atrial fibrillation and oral anticoagulation status, seems safe and may reduce cerebrovascular events in long-term follow-up. More extensive randomized clinical trials investigating left atrial appendage closure in patients without atrial fibrillation and high stroke risk are warranted.

Impact of MRI on decision-making in ICU patients with disorders of consciousness.

BACKGROUND: Recovery of consciousness is the most important survival factor in patients with acute brain injury and disorders of consciousness (DoC). Since most deaths in the intensive care unit (ICU) occur after withdrawal of life-support, medical decision-making is crucial for acute DoC patients. Neuroimaging informs decision-making, yet the precise effects of MRI on decision-making in the ICU are poorly understood. We investigated the impact of brain MRI on prognostication, therapeutic decisions and physician confidence in ICU patients with DoC. METHODS: In this simulated decision-making study utilizing a prospective ICU cohort, a panel of neurocritical experts first reviewed clinical information (without MRI) from 75 acute DoC patients and made decisions about diagnosis, prognosis and treatment. Following review of the MRI, the panel then decided if the initial decisions needed revision. In parallel, a blinded neuroradiologist reassessed all neuroimaging. RESULTS: MRI led to changes in clinical management of 57 (76%) of patients (Number-Needed-to-Test for any change: 1.32), including revised diagnoses (20%), levels of care (21%), diagnostic confidence (43%) and prognostications (33%). Decisions were revised more often with stroke than with other brain injuries (p = 0.02). However, although MRI revealed additional pathology in 81%, this did not predict revised clinical decision-making (p-values ≥0.08). CONCLUSION: MRI results changed decision-making in 3 of 4 ICU patients, but radiological findings were not predictive of clinical decision-making. This highlights the need to better understand the effects of neuroimaging on management decisions. How MRI influences decision-making in the ICU is an important avenue for research to improve acute DoC management.

Less Severe Preoperative Synovitis is Associated With Higher Self-reported Pain Intensity 12 Months After Total Knee Arthroplasty-An Exploratory Prospective Observational Study.

OBJECTIVES: Synovitis is one of the possible pain generators in osteoarthritis (OA) and is associated with upregulation of proinflammatory cytokines, which can lead to worsening of the postoperative pain. This exploratory study aimed to investigate the association between perioperative synovitis and self-reported pain 12 months after total knee arthroplasty (TKA) in patients with OA. MATERIALS AND METHODS: Twenty-six knee OA patients were included in this analysis. The perioperative volume of synovitis in predefined locations was assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Perioperative synovitis was assessed histologically from biopsies of the synovium. Highest pain intensity within the last 24 hours (Visual Analog Scale, VAS, 0 to 100) was assessed before and 12 months after TKA. Patients were divided into a low-pain intensity (VAS≤30) and a high-pain intensity (VAS>30) group on the basis of 12 months postoperative VAS. RESULTS: The high-pain intensity group had significantly lower perioperative contrast-enhanced-synovitis (P=0.025), DCE-synovitis (P<0.04), and a trend toward lower histologically assessed synovitis (P=0.077) compared with the low-pain intensity group. Perioperative synovitis scores were inversely correlated with pain intensity 12 months after TKA (P<0.05), indicating that more severe perioperative synovitis is associated with less severe pain intensity at 12 months. DISCUSSION: Higher degrees of perioperative synovitis scores are found to be associated with less postoperative pain 12 months after TKA. Further, correlation analysis revealed that less severe perioperative CE-MRI and DCE-MRI synovitis was associated with higher pain intensity 12 months after TKA, suggesting that CE-MRI and DCE-MRI synovitis grades could be used as imaging markers for prediction of chronic postoperative pain after TKA.

Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study.

BACKGROUND: Open heart surgery is associated with high occurrence of atrial fibrillation (AF), subsequently increasing the risk of post-operative ischemic stroke. Concomitant with open heart surgery, a cardiac ablation procedure is commonly performed in patients with known AF, often followed by left atrial appendage closure with surgery (LAACS). However, the protective effect of LAACS on the risk of cerebral ischemia following cardiac surgery remains controversial. We have studied whether LAACS in addition to open heart surgery protects against post-operative ischemic brain injury regardless of a previous AF diagnosis. METHODS: One hundred eighty-seven patients scheduled for open heart surgery were enrolled in a prospective, open-label clinical trial and randomized to concomitant LAACS vs. standard care. Randomization was stratified by usage of oral anticoagulation (OAC) planned to last at least 3 months after surgery. The primary endpoint was a composite of post-operative symptomatic ischemic stroke, transient ischemic attack or imaging findings of silent cerebral ischemic (SCI) lesions. RESULTS: During a mean follow-up of 3.7 years, 14 (16%) primary events occurred among patients receiving standard surgery vs. 5 (5%) in the group randomized to additional LAACS (hazard ratio 0.3; 95% CI: 0.1-0.8, p = 0.02). In per protocol analysis (n = 141), 14 (18%) primary events occurred in the control group vs. 4 (6%) in the LAACS group (hazard ratio 0.3; 95% CI: 0.1-1.0, p = 0.05). CONCLUSIONS: In a real-world setting, LAACS in addition to elective open-heart surgery was associated with lower risk of post-operative ischemic brain injury. The protective effect was not conditional on AF/OAC status at baseline. TRIAL REGISTRATION: LAACS study, clinicaltrials.gov NCT02378116 , March 4th 2015, retrospectively registered.

Conventional Supine MRI With a Lumbar Pillow-An Alternative to Weight-bearing MRI for Diagnosing Spinal Stenosis?: A Cross-sectional Study.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To investigate if adding a lumbar pillow in supine position during magnetic resonance imaging (MRI) is superior to standing positional MRI for diagnosing lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: The upright standing position and especially extension of the lumbar spine seem to worsening symptoms of LSS. However, it is unclear whether a forced lumbar extension by a pillow in the lower back during conventional supine MRI may improve the diagnostics of LSS compared with standing MRI. METHODS: Patients suspected for LSS and referred to conventional MRI were included to an additional positional MRI scan (0.25T G-Scan) performed in: (1) conventional supine, (2) standing, (3) supine with a lumbar pillow in the lower back. LSS was evaluated for each position in consensus on a 0 to 3 semi-quantitative grading scale. Independently, L2-S1 lordosis angle, spinal cross-sectional diameter (SCSD), dural cross-sectional diameter (DCSD), and dural cross-sectional diameter (DCSA) were measured. The smallest dural diameter was defined as stenosis level and the largest control level for comparison. RESULTS: Twenty-seven patients (60.6 years; ±9.4) were included. The lordosis angle increased significantly from supine to standing (3.2° CI: 1.2-5.2) and with the lumbar pillow (12.8° CI: 10.3-15.3). One-way analysis of variance (ANOVA) showed significant differences between positions (P < 0.001). When compared with the supine position, pairwise comparisons showed decreased SCSD, DCSD, DCSA, and increasing semi-quantitative grading, during both standing and supine with the lumbar pillow. A difference in the semi-quantitative grades was only found between standing and supine with a lumbar pillow, and the scan with a lumbar pillow was significantly more painful. CONCLUSION: Standing MRI and supine MRI with a lumbar pillow resulted in equal changes in the lumbar spine, although standing MRI may be more sensitive in the assessment of patients suspected for LSS. LEVEL OF EVIDENCE: 2.

Synovitis assessed on static and dynamic contrast-enhanced magnetic resonance imaging and its association with pain in knee osteoarthritis: A cross-sectional study.

OBJECTIVES: To investigate the association between pain and peripatellar-synovitis on static and dynamic contrast-enhanced MRI in knee osteoarthritis. METHODS: In a cross-sectional setting, knee synovitis was assessed using 3-Tesla MRI and correlated with pain using the knee injury and osteoarthritis outcome score (KOOS). Synovitis was assessed in the peripatellar recesses with: (i) dynamic contrast-enhanced (DCE)-MRI, using both pharmacokinetic and heuristic models, (ii) contrast-enhanced (CE)-MRI, and (iii) non-CE-MRI. The DCE-MRI variable IRExNvoxel was chosen as the primary variable in the analyses. RESULTS: Valid data were available in 94 persons with a mean age of 65 years, a BMI of 32.3kg/m(2) and a mean Kellgren-Lawrence grade of 2.5. IRExNvoxel showed a statically significant correlation with KOOS-Pain (r=-0.34; p=0.001), as was the case with all DCE-variables but one. Correlations between static MRI-variables and KOOS-Pain ranged between -0.21

Effect of Lumbar Disc Degeneration and Low-Back Pain on the Lumbar Lordosis in Supine and Standing: A Cross-Sectional MRI Study.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To examine the influence of low-back pain (LBP) and lumbar disc degeneration (LDD) on the lumbar lordosis in weight-bearing positional magnetic resonance imaging (pMRI). SUMMARY OF BACKGROUND DATA: The lumbar lordosis increases with a change of position from supine to standing and is known as an essential contributor to dynamic changes. However, the lordosis may be affected by disc degeneration and pain. METHODS: Patients with LBP >40 on a 0 to 100 mm Visual Analog Scale (VAS) both during activity and rest and a sex and age-decade matching control group without LBP were scanned in the supine and standing position in a 0.25-T open MRI unit. LDD was graded using Pfirrmann's grading-scale. Subsequently, the L2-to-S1 lumbar lordosis angle (LA) was measured. RESULTS: Thirty-eight patients with an average VAS of 58 (±13.8) mm during rest and 75 (±5.0) mm during activities, and 38 healthy controls were included. MRI findings were common in both groups, whereas, the summation of the Pfirrmann's grades (LDD-score) was significantly higher in the patients [(MD 1.44; 95% confidence intervals (CI) 0.80 to 2.10; P < 0.001]. The patients were less lordotic than the controls in both the supine (MD -6.4°; 95% CI -11.4 to -1.3), and standing position (MD -5.6°; 95% CI -10.7 to -0.7); however, the changes between the positions (ΔLA) were the same (MD 0.8°; 95% CI -1.8 to 3.3). Using generalized linear model the LDD-score was associated with age (P < 0.001) for both groups. The LDD-score and ΔLA were negatively associated in the control group (P < 0.001), also after adjustments for gender and age (ß-coefficient: -2.66; 95% CI -4.3 to -1.0; P = 0.002). CONCLUSION: Patients may be less lordotic in both the supine and standing position, whereas, change in the lordosis between the positions may be independent of pain. Decreasing lordosis change seems to be associated with age-related increasing disc degeneration in healthy individuals. LEVEL OF EVIDENCE: 2.