3414 Association of blood pressure and biochemical knee cartilage composition assessed by T2 relaxation time measurements: Data from the Osteoarthritis Initiative

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to investigate the associations of systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) with knee articular cartilage composition using magnetic resonance imaging (MRI)-based T2 relaxation time measurements in study participants from the Osteoarthritis Initiative (OAI). METHODS/STUDY POPULATION: In this longitudinal study, 1,139 participants from the OAI, a multi-center, observational study of the evolution of knee OA, were selected using the following inclusion criteria: right knee Kellgren Lawrence (KL) score (radiographic classification of OA severity) 0-2 indicating no to mild radiographic OA at baseline, no history of rheumatoid arthritis at baseline, available blood pressure measurements at baseline, available T2 measurements in at least three knee compartments at baseline and 48-month follow-up. Linear regression models were performed using standardized values for SBP, DBP and PP as primary predictors and change in cartilage T2 over 48 months, a measure of cartilage matrix quality and degeneration, as the primary outcome. PP was defined as SBP minus DBP. Change in superficial layer and deep layer cartilage T2, which reflect differences in the laminar organization of knee cartilage T2, were also included as outcomes. Statistical models were adjusted for common risk factors for knee OA (baseline age, sex, BMI, KL score) as well as number of currently used anti-hypertensive medications (AHM) reported at baseline. We included AHMs whose primary indication was the treatment of hypertension including beta blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), thiazides, chlorthalidone, dihydropyridine calcium channel blockers (CCB) and aliskiren. All predictors, outcomes and covariates (except sex) were analyzed as continuous variables. We included interaction terms in the models to evaluate whether the covariates (age, sex, BMI, KL score, number of AHMs) modified the association of SBP, DBP and PP with cartilage T2. RESULTS/ANTICIPATED RESULTS: The average age of all study participants was 58.8 years (SD ± 8.6) with a higher proportion of men (59.4%), average body mass index (BMI) was 28.3 (SD ± 4.5), average SBP was 122.4 (SD ± 15.4) mmHg, average DBP was 75.5 (SD ± 9.6) mmHg and 469 (38.1%) study participants were taking at least one AHM. Higher baseline DBP was significantly associated with a faster increase in global T2 (0.22 [0.10,0.35], P < 0.001), global deep layer T2 (0.20 [0.03,0.36], P < 0.022) and global superficial layer T2 (0.39 [0.20,0.58], P < 0.001). These associations were significant in both unadjusted and the models adjusted for age, sex, BMI and KL score. No significant associations were found between SBP or PP and cartilage T2 and no significant interactions were found between SBP, DBP, PP and the covariates. DISCUSSION/SIGNIFICANCE OF IMPACT: Higher baseline DBP was associated with a faster increase in knee cartilage T2, suggesting accelerated cartilage degeneration. This association was stronger for the superficial layer of knee cartilage T2 compared to the deep layer. Although further basic mechanistic studies are needed to elucidate the underlying pathophysiology of this relationship, these results suggest lowering DBP may influence knee OA

Association of blood pressure with knee cartilage composition and structural knee abnormalities: data from the osteoarthritis initiative.

ObjectiveTo investigate the associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with changes in knee cartilage composition and joint structure over 48 months, using magnetic resonance imaging (MRI) data from the Osteoarthritis Initiative (OAI).Materials and methodsA total of 1126 participants with right knee Kellgren-Lawrence (KL) score 0-2 at baseline, no history of rheumatoid arthritis, blood pressure measurements at baseline, and cartilage T2 measurements at baseline and 48 months were selected from the OAI. Cartilage composition was assessed using MRI T2 measurements, including laminar and gray-level co-occurrence matrix texture analyses. Structural knee abnormalities were graded using the whole-organ magnetic resonance imaging score (WORMS). We performed linear regression, adjusting for age, sex, body mass index, physical activity, smoking status, alcohol use, KL score, number of anti-hypertensive medications, and number of nonsteroidal anti-inflammatory drugs.ResultsHigher baseline DBP was associated with greater increases in global T2 (coefficient 0.22 (95% CI 0.09, 0.34), P = 0.004), global superficial layer T2 (coefficient 0.39 (95% CI 0.20, 0.58), P = 0.001), global contrast (coefficient 15.67 (95% CI 8.81, 22.53), P < 0.001), global entropy (coefficient 0.02 (95% CI 0.01, 0.03) P = 0.011), and global variance (coefficient 9.14 (95% CI 5.18, 13.09), P < 0.001). Compared with DBP, the associations of SBP with change in cartilage T2 parameters and WORMS subscores showed estimates of smaller magnitude.ConclusionHigher baseline DBP was associated with higher and more heterogenous cartilage T2 values over 48 months, indicating increased cartilage matrix degenerative changes

Associations between alcohol, smoking, and cartilage composition and knee joint morphology: Data from the Osteoarthritis Initiative

Summary: Objective: To determine the cross-sectional associations of alcohol consumption and smoking history with magnetic resonance imaging (MRI) measures of cartilage composition (T2) and joint structure using data from the Osteoarthritis Initiative (OAI). Design: Subjects with radiographic Kellgren Lawrence right knee grades 0–2 were selected from the OAI database, and those with previously analyzed MRI cartilage T2 and semi-quantitative joint morphology gradings (WORMS) were included (n ​= ​2061). Alcohol consumption was categorized as: no drinks to 7 drinks/week. Smoking history was categorized as none, current, or former. Linear regression was used to assess the relationships of alcohol consumption and smoking history with both WORMS scores and cartilage T2. Results: Subjects who consumed >7 drinks/week had significantly higher cartilage T2 than subjects who consumed 7 drinks/week was associated with elevated cartilage T2. Compared to non-smokers, current smokers had a more degenerated cartilage matrix as evidenced by greater cartilage T2

Automated Opportunistic Osteoporosis Screening in Routine Computed Tomography of the Spine: Comparison With Dedicated Quantitative CT

Opportunistic osteoporosis screening in nondedicated routine computed tomography (CT) is of increasing importance. The purpose of this study was to compare lumbar volumetric bone mineral density (vBMD) assessed by a convolutional neural network (CNN)-based framework in routine CT to vBMD from dedicated quantitative CT (QCT), and to evaluate the ability of vBMD and surrogate measurements of Hounsfield units (HU) to distinguish between patients with and without osteoporotic vertebral fractures (VFs). A total of 144 patients (median age: 70.7 years, 93 females) with clinical routine CT (eight different CT scanners, 120 kVp or 140 kVp, with and without intravenous contrast medium) and dedicated QCT acquired within ≤30 days were included. Vertebral measurements included (i) vBMD from the CNN-based approach including automated vertebral body labeling, segmentation, and correction of the contrast media phase for routine CT data (vBMD_OPP), (ii) vBMD from dedicated QCT (vBMD_QCT), and (iii) noncalibrated HU from vertebral bodies of routine CT data as previously proposed for immanent opportunistic osteoporosis screening based on CT attenuation. The intraclass correlation coefficient (ICC) for vBMD_QCT versus vBMD_OPP indicated better agreement (ICC = 0.913) than the ICC for vBMD_QCT versus noncalibrated HU (ICC = 0.704). Bland-Altman analysis showed data points from 137 patients (95.1%) within the limits of agreement (LOA) of -23.2 to 25.0 mg/cm3 for vBMD_QCT versus vBMD_OPP. Osteoporosis (vBMD <80 mg/cm3 ) was detected in 89 patients (vBMD_QCT) and 88 patients (vBMD_OPP), whereas no patient crossed the diagnostic thresholds from normal vBMD to osteoporosis or vice versa. In a subcohort of 88 patients (thoracolumbar spine covered by imaging for VF reading), 69 patients showed one or more prevalent VFs, and the performance for discrimination between patients with and without VFs was best for vBMD_OPP (area under the curve [AUC] = 0.862; 95% confidence interval [CI], 0.771-0.953). In conclusion, automated opportunistic osteoporosis screening in routine CT of various scanner setups is feasible and may demonstrate high diagnostic accuracy for prevalent VFs. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication