Association between changes in knee load and effusion-synovitis: evidence of mechano-inflammation in knee osteoarthritis using high tibial osteotomy as a model

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

Total knee replacement after high tibial osteotomy: Time-to-event analysis and predictors

© 2021 Joule Inc. or its licensors. BACKGROUND: An important aim of high tibial osteotomy (HTO) is to prevent or delay the need for total knee replacement (TKR). We sought to estimate the frequency and timing of conversion from HTO to TKR and the factors associated with it. METHODS: We prospectively evaluated patients with osteoarthritis (OA) of the knee who underwent medial opening wedge HTO from 2002 to 2014 and analyzed the cumulative incidence of TKR in July 2019. The presence or absence of TKR on the HTO limb was identified from the orthopedic surgery reports and knee radiographs contained in the electronic medical records for each patient at London Health Sciences Centre. We used cumulative incidence curves to evaluate the primary outcome of time to TKR. We used multivariable Cox proportional hazards analysis to assess potential preoperative predictors including radiographic disease severity, malalignment, correction size, pain, sex, age, body mass index (BMI) and year of surgery. RESULTS: Among 556 patients who underwent 643 HTO procedures, the cumulative incidence of TKR was 5% (95% confidence interval [CI] 3%–7%) at 5 years and 21% (95% CI 17%–26%) at 10 years. With the Cox proportional hazards multivariable model, the following preoperative factors were significantly associated with an increased rate of conversion: radiographic OA severity (adjusted hazard ratio [HR] 1.96, 95% CI 1.12–3.45), pain (adjusted HR 0.85, 95% CI 0.75–0.96)], female sex (adjusted HR 1.67, 95% CI 1.08–2.58), age (adjusted HR 1.50 per 10 yr, 95% CI 1.17–1.93) and BMI (adjusted HR 1.31 per 5 kng/m2, 95% CI 1.12–1.53). INTERPRETATION: We found that 79% of knees did not undergo TKR within 10 years after undergoing medial opening wedge HTO. The strongest predictor of conversion to TKR is greater radiographic disease at the time of HTO

Radiocarbon constraints on the glacial ocean circulation and its impact on atmospheric CO2

While the ocean’s large-scale overturning circulation is thought to have been significantly different under the climatic conditions of the Last Glacial Maximum (LGM), the exact nature of the glacial circulation and its implications for global carbon cycling continue to be debated. Here we use a global array of ocean–atmosphere radiocarbon disequilibrium estimates to demonstrate a ∼689±53 14C-yr increase in the average residence time of carbon in the deep ocean at the LGM. A predominantly southern-sourced abyssal overturning limb that was more isolated from its shallower northern counterparts is interpreted to have extended from the Southern Ocean, producing a widespread radiocarbon age maximum at mid-depths and depriving the deep ocean of a fast escape route for accumulating respired carbon. While the exact magnitude of the resulting carbon cycle impacts remains to be confirmed, the radiocarbon data suggest an increase in the efficiency of the biological carbon pump that could have accounted for as much as half of the glacial–interglacial CO2 change

Are we missing the target? Are we aiming too low? What are the aerobic exercise prescriptions and their effects on markers of cardiovascular health and systemic inflammation in patients with knee osteoarthritis? A systematic review and meta-analysis

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Objectives We 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 sources PubMed, CINAHL, Scopus; inception to January 2019. Eligibility criteria Randomised clinical trials (RCT), cohort studies, case series. Design We 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 (VO 2), 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. Results Interventions 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 VO 2 (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. Conclusions In 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 number CRD42018087859

Sleep disruption due to nocturnal heartburn: a review of the evidence and clinical implications

Nocturnal heartburn (NHB) is a symptom that affects up to 25% of the general population and has been shown to cause sleep disruption that adversely affects quality of life and psychomotor performance. Few studies have evaluated the association between occasional NHB and sleep disturbances; therefore, this connection may be underappreciated and left untreated by the primary care provider and patient, with potentially significant negative clinical consequences and effects on quality of life. This review sought to describe what is currently known about the interplay between occasional NHB and sleep disruption, and identify whether acid suppression therapy can improve symptoms of occasional NHB and associated sleep disruptions. The pathophysiology of heartburn-induced sleep disruption appears to follow a bidirectional cycle due to the normal physiologic changes that occur in the upper gastrointestinal tract during sleep and due to the potential for heartburn symptoms to cause sleep arousal. The majority of the identified studies suggested that pharmacologic interventions for acid reduction, including proton pump inhibitors or histamine type-2 receptor antagonists (H2RAs), improved objective and/or subjective sleep outcomes among individuals with gastroesophageal reflux disease (GERD) and NHB. Several studies specific to famotidine demonstrated that treatment with 10 mg or 20 mg reduced nighttime awakenings due to NHB. In conclusion, NHB symptoms can cause sleep dysfunction that can have a profound adverse downstream effect on quality of life, next-day functioning, and health-related outcomes. The current approach to managing occasional NHB is similar to that associated with GERD, highlighting the need for studies specific to the occasional heartburn population. Health care providers should investigate NHB as one of the potential causes of sleep complaints, and patients with heartburn should be questioned about sleep quality, recalled arousals, next-day vitality, early fatigue, and next-day functioning

Flux Distributions as Robust Diagnostics of Stratosphere-Troposphere Exchange

We perform the first analysis of stratosphere-troposphere exchange in terms of distributions that partition the one-way flux across the thermal tropopause according to stratospheric residence time τ and the regions where air enters and exits the stratosphere. These distributions robustly quantify one-way flux without being rendered ill defined by the short-τ eddy-diffusive singularity. Diagnostics are computed with an idealized circulation model with topography only in the Northern Hemisphere (NH) run under perpetual NH winter conditions. Suitable integrations of the flux distribution are used to determine the stratospheric mean residence time inline image and the mass fraction of the stratosphere in any given residence time interval. We find that the largest mass fraction is destined for isentropic cross-tropopause transport, with one-way fluxes that are sustained over a broad range of residence times. Air exiting the stratosphere in the winter hemisphere has significantly longer mean residence times than air exiting in the summer hemisphere because the winter hemisphere has a deeper circulation and stronger eddy diffusion. We also explore the sensitivity of the stratosphere-troposphere exchange to changes in the circulation by increasing the amplitude of the topography. The resulting more vigorous residual mean circulation dominates over increased eddy diffusion, leading to decreased inline image except for air exiting at high NH latitudes, for which inline image increases. These findings underline that the flux distributions diagnose the integrated advective-diffusive tropopause-to-tropopause transport and not merely advection by the residual mean circulation

Radiocarbon constraints on the glacial ocean circulation and its impact on atmospheric CO2_2

While the ocean's large-scale overturning circulation is thought to have been significantly different under the climatic conditions of the Last Glacial Maximum (LGM), the exact nature of the glacial circulation and its implications for global carbon cycling continue to be debated. Here we use a global array of ocean-atmosphere radiocarbon disequilibrium estimates to demonstrate a ~689±53 $^{14}$C-yr increase in the average residence time of carbon in the deep ocean at the LGM. A predominantly southern-sourced abyssal overturning limb that was more isolated from its shallower northern counterparts is interpreted to have extended from the Southern Ocean, producing a widespread radiocarbon age maximum at mid-depths and depriving the deep ocean of a fast escape route for accumulating respired carbon. While the exact magnitude of the resulting carbon cycle impacts remains to be confirmed, the radiocarbon data suggest an increase in the efficiency of the biological carbon pump that could have accounted for as much as half of the glacial-interglacial CO$_2$ change.This work was made possible by NERC grant NE/L006421/1, and was supported by NERC radiocarbon analysis allocation number 1245.1007, as well as the Royal Society and the Cambridge Isaac Newton Trust

On the formation, ventilation, and erosion of mode waters in the North Atlantic and Southern Oceans

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94834/1/jgrc12564.pd