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The purpose of this study was to: (1) test the hypothesis that HTO improves articular cartilage composition in the medial compartment without adversely affecting the lateral compartment and patella, and; (2) explore associations between knee alignment and cartilage composition after surgery. 3T MRI and standing radiographs were obtained from 34 patients before and 1-year after HTO. Articular cartilage was segmented from T2 maps. Mechanical axis angle (MAA), posterior tibial slope, and patellar height were measured from radiographs. Changes in T2 and radiographic measures were assessed using paired t tests, and associations were assessed using Pearson correlation coefficients. The mean (SD) MAA before and after HTO was − 6.5° (2.4) and 0.6° (3.0), respectively. There was statistically significant shortening [mean (95%CI)] of T2 in the medial femur [− 2.8 ms (− 4.2; − 1.3), p

ObjectivesWe systemically reviewed published studies that evaluated aerobic exercise interventions in patients with knee osteoarthritis (OA) to: (1) report the frequency, intensity, type and time (FITT) of exercise prescriptions and (2) quantify the changes in markers of cardiovascular health and systemic inflammation.Data sourcesPubMed, CINAHL, Scopus; inception to January 2019.Eligibility criteriaRandomised clinical trials (RCT), cohort studies, case series.DesignWe summarised exercise prescriptions for all studies and calculated effect sizes with 95% CIs for between-group (RCTs that compared exercise and control groups) and within-group (pre-post exercise) differences in aerobic capacity (VO2), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and inflammatory markers (interleukin-6 (IL-6), tumour necrosis factor-alpha). We pooled results where possible using random effects models.ResultsInterventions from 49 studies were summarised; 8% (4/49) met all FITT guidelines; 16% (8/49) met all or most FITT guidelines. Fourteen studies (10 RCTs) reported at least one marker of cardiovascular health or systemic inflammation. Mean differences (95% CI) indicated a small to moderate increase in VO2 (0.84 mL/min/kg; 95% CI 0.37 to 1.31), decrease in HR (−3.56 beats per minute; 95% CI −5.60 to −1.52) and DBP (−4.10 mm Hg; 95% CI −4.82 to −3.38) and no change in SBP (−0.36 mm Hg; 95% CI −3.88 to 3.16) and IL-6 (0.37 pg/mL; 95% CI −0.11 to 0.85). Within-group differences were also small to moderate.ConclusionsIn studies of aerobic exercise in patients with knee OA, very few interventions met guideline-recommended dose; there were small to moderate changes in markers of cardiovascular health and no decrease in markers of systemic inflammation. These findings question whether aerobic exercise is being used to its full potential in patients with knee OA.PROSPERO registration numberCRD42018087859.

Objectives: The purpose of this study is to evaluate whether augmentation of anterior cruciate ligament reconstruction (ACLR) with a lateral extra-articular tenodesis (LET) affects articular cartilage morphology on magnetic resonance imaging (MRI) two years post-operatively in a young, active population. Methods: Ninety-seven patients at the Fowler Kennedy Sports Medicine Clinic participating in the Stability study, a multi-center randomized controlled trial of 618 patients comparing ACLR ± LET, underwent bilateral 3T MRI at two-years post-surgery. Quantitative MRI (qMRI) pulse sequences consist of a Sagittal Multi-Echo Spin Echo T2 Mapping sequence, and a 16-shot Gradient Echo T1rho Mapping sequence. The primary imaging outcome was T1rho and T2 relaxation time. Articular cartilage was manually segmented on three consecutive load-bearing slices by three independent raters, and values were averaged for three regions on the tibia and five regions on the femur in both the medial and lateral compartments. Raters were blind to scan order and an ICC (2,1) was used to assess inter-rater reliability. Independent t-tests were used to compare relaxation times between groups in each compartment. Results: Ninety-seven participants (47 ACL, 50 ACL+LET), including 59.7% (58/97) females with a mean age of 18.9 years underwent MRI 2-years post-op (range = 20 to 36 months). Currently, 41 scans (23 ACL, 18 ACL+LET) have been analyzed. There were no significant differences between groups for regions in the medial compartment. T2 relaxation times were significantly higher for the ACL+LET group in the central and posterolateral (PL) tibia and the PL femur (Table 1). T1rho relaxation times were significantly lower for the ACL+LET group in the proximal posterior femur. Raters showed good inter-rater reliability with an ICC of 0.85.. Conclusions: T2 relaxation times are elevated in the lateral compartment following ACLR augmented by LET compared to ACLR alone however, the clinical significance is not currently clear as the differences were small (

Summary Objective Although mechanically-induced inflammation is an appealing explanation linking different etiologic factors in osteoarthritis (OA), clinical research investigating changes in both biomechanics and joint inflammation is limited. The purpose of this study was to evaluate the association between change in surrogate measures of knee load and knee effusion-synovitis in patients with medial compartment knee OA undergoing high tibial osteotomy (HTO). Methods Thirty-six patients with medial compartment knee OA and varus alignment underwent 3D gait analysis and 3T magnetic resonance imaging (MRI) preoperatively and 1 year after medial opening wedge HTO. Primary outcome measures were the change in the external knee adduction moment impulse during walking and change in knee suprapatellar effusion-synovitis volume manually segmented on MRI by one blinded assessor. Results Mean (SD) knee adduction moment impulse [24.0 (6.5) Nm•s] and knee effusion-synovitis volume [8976.7 (8016.9) mm3] suggested substantial preoperative medial knee load and inflammation. 1-year postoperative changes in knee adduction moment impulse [−10.1 Nm•s (95%CI: −12.7, −7.4)], and knee effusion-synovitis volume [−1856 mm3 (95%CI: −3830, 117)] were positively correlated [r = 0.60 (95% CI 0.34, 0.78)]. Simple linear regression suggested a 448 mm3 (95%CI: 241, 656) reduction in knee effusion-synovitis volume per 1 Nm•s reduction in knee adduction moment impulse. Change in knee adduction moment impulse explained 36% (R2 = 0.36) of the variance of change in knee effusion-synovitis volume. Conclusions Reduction in medial knee load is positively associated with reduction in knee inflammation after HTO, suggesting the phenomenon of mechano-inflammation in patients with knee OA.

© 2018 The Authors Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society New Findings: What is the central question of this study? Nitric oxide causes dilatation in peripheral vessels; however, whether nitric oxide affects basal cerebral artery dilatation has not been explored. What is the main finding and its importance? This study demonstrated that vasodilatation occurs in the right middle cerebral artery in response to exogenous nitric oxide. However, blood velocity decreased and, therefore, overall cerebral blood flow remained unchanged. This study provides new insight into the role of nitric oxide in cerebral blood flow control. Abstract: Recent evidence indicates that basal cerebral conduit vessels dilate with hypercapnia, with a nitric oxide (NO) mechanism explaining one way in which parenchymal cerebral arterioles dilate. However, whether NO affects basal cerebral artery dilatation remains unknown. This study quantified the effect of an exogenous NO donor [sodium nitroglycerin (NTG); 0.4 mg sublingual spray] on the right middle cerebral artery (rMCA) cross-sectional area (CSA), blood velocity and overall blood flow. Measures of vessel CSA (7 T magnetic resonance imaging) and MCA blood velocity (transcranial Doppler ultrasound) were made at baseline (BL) and after exogenous NTG or placebo (PLO) administration in young, healthy individuals (n = 10, two males, age range 20–23 years). The CSA increased in the rMCA [BL, 5.2 ± 1.2 mm2; PLO, 5.4 ± 1.5 mm2; NTG, 6.6 ± 1.5 mm2, P < 0.05; mean ± SD]. Concurrently, rMCA blood velocity decreased from BL during NTG compared with PLO (BL, 67 ± 10 cm s−1; PLO, 62 ± 10 cm s−1; NTG, 59 ± 9.3 cm s−1, P < 0.05; mean ± SD]. However, total MCA blood flow did not change with NTG or PLO [BL, 221 ± 37.4 ml min−1; PLO, 218 ± 35.0 ml min−1; NTG, 213 ± 46.4 ml min−1). Therefore, exogenous NO mediates a dilatory response in the rMCA, but not in its downstream vascular bed.

Background:The Knee Inflammation MRI Scoring System (KIMRISS) is a semi-quantitative grading tool (range 0-500) used to measure features of inflammation in knee osteoarthritis (OA), including compartment-specific BML scores.Objectives:To investigate; 1) Inter-rater reliability of KIMRISS BML change scores including expert readers and a trainee reader, 2) Validity of KIMRISS BML scores by comparing medial and lateral femoral compartments in surgical and contralateral limbs before and 1 year after medial opening wedge high tibial osteotomy (HTO).Methods:We included 27 patients with varus alignment and medial compartment knee OA [preoperative Kellgren-Lawrence grades ≤3, age = 53.1 ± 5.9, 22 males (81%), body mass index = 29.9 ± 4.3] undergoing unilateral HTO. Sagittal 2D turbo spin-echo sequences were acquired at 3-Tesla in both knees pre and 1-year post HTO after surgical removal of hardware. Femoral BML scores in the medial and lateral compartments were assessed on images blinded to limb and time by masking surgical evidence. Three reviewers independently graded the same 108 images (27 patients, 2 limbs, 2 time points). We evaluated reliability pre-to-post HTO BML change scores in the medial and lateral femur by calculating intraclass correlation coefficients (ICC) and Bland-Altman plots with 80% Limits of Agreement (LoA) for each rater pair.Results:Means and standard deviations are shown in Figure 1. Cumulative percent distribution plots of changes after surgery show both increases and decreases in the medial and lateral femur (Figure 2). When combining all raters, the ICC (95% confidence interval (CI)) for the change in BML score for the surgical knee was 0.81(0.64, 0.91) in the medial femur and 0.73 (0.49, 0.87) in the lateral femur. 80% LOA for change in BML score in the surgical knee was -3.56 to 5.44. ICCs and LoAs for rater pairs are in Table 1. The surgical limb medial femur BML score was significantly greater than all other scores pre and post HTO (Figure 1). There were no significant changes after HTO. The mean change (95% CI) in medial femur BML score of the surgical knee was 1.08 (-1.21, 3.38). Using the mean scores of all raters, we compared BML scores in surgical and contralateral limbs before and after HTO using a 2-way repeated measures (limb by time) ANOVA, seperately for the medial and lateral compartments.Table.Intraclass Correlation Coefficients (95% Confidence Intervals) and 80% Limits of Agreement for change in BMLs scores in the surgical knee.a)Medial compartment12310.63 (0.34, 0.81)230.69 (0.43, 0.85)0.42 (0.06, 0.69)b)Lateral compartment123120.67 (0.41, 0.83)30.79 (0.60, 0.90)0.47 (0.11, 0.72)c)Medial compartment12313-6.09, 8.614-8.10, 9.65-6.03, 7.58d)Lateral compartment12312-3.49, 5.413-4.73, 6.99-3.43, 4.95ICCs in the medial (a) and lateral (b) compartments, and 80% LoA in the medial (c) and lateral (d) compartments. Rater 1 = trainee reader, raters 2-3 = expert readers (one MSK radiologist and one rheumatologist).Fig 1.Means and standard deviations for KIMRISS femoral BML scores in the medial and lateral compartment for the surgical and contralateral knee.Fig 2.Probability plots for the 12-month change after surgery in femoral BML score in the medial (a) and lateral (b) compartments of the surgical knee. Change scores from each of the three raters is shown, as well as the average of all four raters.Conclusion:The KIMRISS can reliably detect differences between femoral BML scores in symptomatic and contralateral limbs, supporting the inter-rater reliability, feasibility and validity of compartment-specific BML scores.Disclosure of Interests:Jenna Schulz: None declared, Trevor Birmingham: None declared, Walter P Maksymowych Grant/research support from: Received research and/or educational grants from Abbvie, Novartis, Pfizer, UCB, Consultant of: WPM is Chief Medical Officer of CARE Arthritis Limited, has received consultant/participated in advisory boards for Abbvie, Boehringer, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Received speaker fees from Abbvie, Janssen, Novartis, Pfizer, UCB., Robert G Lambert: None declared, Stephany Pritchett: None declared, Frank Beier: None declared, J. Robert Giffin: None declared, Thomas Appleton Grant/research support from: AbbVie and Pfizer