Cerebral Small Vessel Disease burden is increased in Systemic Lupus Erythematosus

BACKGROUND AND PURPOSE—: Systemic lupus erythematosus (SLE) increases stroke risk, but the mechanism is uncertain. This study aimed to determine the association between SLE and features on neuroimaging of cerebral small vessel disease (SVD), a risk factor for stroke. METHODS—: Consecutive patients attending a clinic for SLE were recruited. All patients underwent brain magnetic resonance imaging; had blood samples taken for markers of inflammation, endothelial dysfunction, cholesterol, and autoantibodies; and underwent cognitive and psychiatric testing. The data were compared with sex- and age-matched healthy controls and patients with minor stroke. Features of SVD were measured, a total SVD score calculated, and associations sought with vascular risk factors, cognition, SLE activity, and disease duration. RESULTS—: Fifty-one SLE patients (age: 48.8 years; SD: 14.3 years) had a greater total SVD score compared with healthy controls (1 versus 0; P<0.0001) and stroke patients (1 versus 0; P=0.02). There were higher perivascular spaces and deep white matter hyperintensity scores and more superficial brain atrophy in SLE patients versus healthy controls. Despite fewer vascular risk factors than similarly aged stroke patients, SLE patients had similar or more of some SVD features. The total SVD score was not associated with SLE activity, cognition, disease duration, or any blood measure. CONCLUSIONS—: In this data set, SLE patients had a high burden of SVD features on magnetic resonance imaging, particularly perivascular spaces. A larger longitudinal study is warranted to determine the causes of SVD features in SLE and clinical implications

Comparison of structural MRI brain measures between 1.5 and 3T: Data from the Lothian Birth Cohort 1936

Multi‐scanner MRI studies are reliant on understanding the apparent differences in imaging measures between different scanners. We provide a comprehensive analysis of T(1)‐weighted and diffusion MRI (dMRI) structural brain measures between a 1.5 T GE Signa Horizon HDx and a 3 T Siemens Magnetom Prisma using 91 community‐dwelling older participants (aged 82 years). Although we found considerable differences in absolute measurements (global tissue volumes were measured as ~6–11% higher and fractional anisotropy [FA] was 33% higher at 3 T than at 1.5 T), between‐scanner consistency was good to excellent for global volumetric and dMRI measures (intraclass correlation coefficient [ICC] range: .612–.993) and fair to good for 68 cortical regions (FreeSurfer) and cortical surface measures (mean ICC: .504–.763). Between‐scanner consistency was fair for dMRI measures of 12 major white matter tracts (mean ICC: .475–.564), and the general factors of these tracts provided excellent consistency (ICC ≥ .769). Whole‐brain structural networks provided good to excellent consistency for global metrics (ICC ≥ .612). Although consistency was poor for individual network connections (mean ICCs: .275−.280), this was driven by a large difference in network sparsity (.599 vs. .334), and consistency was improved when comparing only the connections present in every participant (mean ICCs: .533–.647). Regression‐based k‐fold cross‐validation showed that, particularly for global volumes, between‐scanner differences could be largely eliminated (R (2) range .615–.991). We conclude that low granularity measures of brain structure can be reliably matched between the scanners tested, but caution is warranted when combining high granularity information from different scanners

Magnetic Resonance Imaging Tissue Signatures Associated With White Matter Changes Due to Sporadic Cerebral Small Vessel Disease Indicate That White Matter Hyperintensities Can Regress

Background White matter hyperintensities (WMHs) might regress and progress contemporaneously, but we know little about underlying mechanisms. We examined WMH change and underlying quantitative magnetic resonance imaging tissue measures over 1 year in patients with minor ischemic stroke with sporadic cerebral small vessel disease. Methods and Results We defined areas of stable normal‐appearing white matter, stable WMHs, progressing and regressing WMHs based on baseline and 1‐year brain magnetic resonance imaging. In these areas we assessed tissue characteristics with quantitative T1, fractional anisotropy (FA), mean diffusivity (MD), and neurite orientation dispersion and density imaging (baseline only). We compared tissue signatures cross‐sectionally between areas, and longitudinally within each area. WMH change masks were available for N=197. Participants' mean age was 65.61 years (SD, 11.10), 59% had a lacunar infarct, and 68% were men. FA and MD were available for N=195, quantitative T1 for N=182, and neurite orientation dispersion and density imaging for N=174. Cross‐sectionally, all 4 tissue classes differed for FA, MD, T1, and Neurite Density Index. Longitudinally, in regressing WMHs, FA increased with little change in MD and T1 (difference estimate, 0.011 [95% CI, 0.006–0.017]; −0.002 [95% CI, −0.008 to 0.003] and −0.003 [95% CI, −0.009 to 0.004]); in progressing and stable WMHs, FA decreased (−0.022 [95% CI, −0.027 to −0.017] and −0.009 [95% CI, −0.011 to −0.006]), whereas MD and T1 increased (progressing WMHs, 0.057 [95% CI, 0.050–0.063], 0.058 [95% CI, 0.050 –0.066]; stable WMHs, 0.054 [95% CI, 0.045–0.063], 0.049 [95% CI, 0.039–0.058]); and in stable normal‐appearing white matter, MD increased (0.004 [95% CI, 0.003–0.005]), whereas FA and T1 slightly decreased and increased (−0.002 [95% CI, −0.004 to −0.000] and 0.005 [95% CI, 0.001–0.009]). Conclusions Quantitative magnetic resonance imaging shows that WMHs that regress have less abnormal microstructure at baseline than stable WMHs and follow trajectories indicating tissue improvement compared with stable and progressing WMHs

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men