Retrospective cohort study to devise a treatment decision score predicting adverse 24-month radiological activity in early multiple sclerosis

Background: Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting about 2.8 million people worldwide. Disease course after the most common diagnoses of relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) is highly variable and cannot be reliably predicted. This impairs early personalized treatment decisions. Objectives: The main objective of this study was to algorithmically support clinical decision-making regarding the options of early platform medication or no immediate treatment of patients with early RRMS and CIS. Design: Retrospective monocentric cohort study within the Data Integration for Future Medicine (DIFUTURE) Consortium. Methods: Multiple data sources of routine clinical, imaging and laboratory data derived from a large and deeply characterized cohort of patients with MS were integrated to conduct a retrospective study to create and internally validate a treatment decision score [Multiple Sclerosis Treatment Decision Score (MS-TDS)] through model-based random forests (RFs). The MS-TDS predicts the probability of no new or enlarging lesions in cerebral magnetic resonance images (cMRIs) between 6 and 24 months after the first cMRI. Results: Data from 65 predictors collected for 475 patients between 2008 and 2017 were included. No medication and platform medication were administered to 277 (58.3%) and 198 (41.7%) patients. The MS-TDS predicted individual outcomes with a cross-validated area under the receiver operating characteristics curve (AUROC) of 0.624. The respective RF prediction model provides patient-specific MS-TDS and probabilities of treatment success. The latter may increase by 5–20% for half of the patients if the treatment considered superior by the MS-TDS is used. Conclusion: Routine clinical data from multiple sources can be successfully integrated to build prediction models to support treatment decision-making. In this study, the resulting MS-TDS estimates individualized treatment success probabilities that can identify patients who benefit from early platform medication. External validation of the MS-TDS is required, and a prospective study is currently being conducted. In addition, the clinical relevance of the MS-TDS needs to be established

Observation of the B0 → ρ0ρ0 decay from an amplitude analysis of B0 → (π+π−)(π+π−) decays

Proton–proton collision data recorded in 2011 and 2012 by the LHCb experiment, corresponding to an integrated luminosity of 3.0 fb−1 , are analysed to search for the charmless B0→ρ0ρ0 decay. More than 600 B0→(π+π−)(π+π−) signal decays are selected and used to perform an amplitude analysis, under the assumption of no CP violation in the decay, from which the B0→ρ0ρ0 decay is observed for the first time with 7.1 standard deviations significance. The fraction of B0→ρ0ρ0 decays yielding a longitudinally polarised final state is measured to be fL=0.745−0.058+0.048(stat)±0.034(syst) . The B0→ρ0ρ0 branching fraction, using the B0→ϕK⁎(892)0 decay as reference, is also reported as B(B0→ρ0ρ0)=(0.94±0.17(stat)±0.09(syst)±0.06(BF))×10−6

Observation of the decay B0s→ψ(2S)K+π−

The decay B¯s0→ψ(2S)K+π− is observed using a data set corresponding to an integrated luminosity of 3.0 fb−1 collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV. The branching fraction relative to the B0→ψ(2S)K+π− decay mode is measured to be B(B¯s0→ψ(2S)K+π−)B(B0→ψ(2S)K+π−)=5.38±0.36(stat)±0.22(syst)±0.31(fs/fd)%, where fs/fd indicates the uncertainty due to the ratio of probabilities for a b quark to hadronise into a Bs0 or B0 meson. Using an amplitude analysis, the fraction of decays proceeding via an intermediate K⁎(892)0 meson is measured to be 0.645±0.049(stat)±0.049(syst) and its longitudinal polarisation fraction is 0.524±0.056(stat)±0.029(syst) . The relative branching fraction for this component is determined to be B(B¯s0→ψ(2S)K⁎(892)0)B(B0→ψ(2S)K⁎(892)0)=5.58±0.57(stat)±0.40(syst)±0.32(fs/fd)%. In addition, the mass splitting between the Bs0 and B0 mesons is measured as M(Bs0)−M(B0)=87.45±0.44(stat)±0.09(syst) MeV/c2

Increased circulating placental growth factor during percutaneous coronary intervention is associated with applied radiocontrast agent

BACKGROUND AND AIM OF THE STUDY: Recent studies have suggested placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) as promising new biomarkers for risk stratification in acute coronary syndromes (ACS). However, little is known about the influence of percutaneous coronary intervention (PCI) on circulating PlGF and VEGF levels. METHODS: Thirty-five patients with ACS, 27 patients with stable coronary artery disease (sCAD), and nine healthy controls were enrolled in the study. Although all patients with ACS and 14 patients with stable angina pectoris underwent PCI, 13 patients with coronary artery disease required no revascularization (sCAD). PlGF and VEGF plasma concentrations were measured by immunoassay during and at the end of PCI and coronary angiography. RESULTS: Plasma PlGF levels were comparable in patients with ACS and sCAD on admission. Although coronary angiography or heparin alone did not alter PlGF and VEGF levels, immediately after PCI a dramatic increase was seen in circulating PlGF and a decrease in VEGF, which was independent of the clinical presentation of the patients, heparin administration, or the angiographic procedure itself, but was associated with the extent of coronary artery disease and the amount of the injected contrast media. In-vitro experiments revealed that radiocontrast agents induced the release of PlGF from endothelial cells without altering PlGF mRNA expression. CONCLUSION: Patients undergoing PCI exhibit an increase in circulating PlGF, probably caused by posttranslational modifications of radiocontrast agents in endothelial cells. Therefore, analysis of plasma PlGF and VEGF levels may consider the timing of blood sampling with respect to PCI and contrast media exposure

Mobilization of CD133+ progenitor cells in patients with acute cerebral infarction.

Progenitor cells (PCs) contribute to the endogenous repair mechanism after ischemic events. Interleukin-8 (IL-8) as part of the acute inflammatory reaction may enhance PC mobilization. Also, statins are supposed to alter number and function of circulating PCs. We aimed to investigate PC mobilization after acute ischemic stroke as well as its association with inflammatory markers and statin therapy. Sixty-five patients with ischemic stroke were enrolled in the study. The number of CD133+ PCs was analyzed by flow cytometry. Blood samples were drawn within 24 hours after symptom onset and after 5 days. The number of CD133+ PCs increased significantly within 5 days (p<0.001). We found no correlation between CD133+ PCs and the serum levels of IL-8, IL-6, or C-reactive protein (CRP). Multivariate analysis revealed that preexisting statin therapy correlated independently with the increase of CD133+ PCs (p=0.001). This study showed a mobilization of CD133+ PCs in patients with acute cerebral infarction within 5 days after symptom onset. The early systemic inflammatory response did not seem to be a decisive factor in the mobilization of PCs. Preexisting statin therapy was associated with the increase in CD133+ PCs, suggesting a potentially beneficial effect of statin therapy in patients with stroke

MRI plaque imaging detects carotid plaques with a high risk for future cerebrovascular events in asymptomatic patients.

PURPOSE: The aim of this study was to investigate prospectively whether MRI plaque imaging can identify patients with asymptomatic carotid artery stenosis who have an increased risk for future cerebral events. MRI plaque imaging allows categorization of carotid stenosis into different lesion types (I-VIII). Within these lesion types, lesion types IV-V and VI are regarded as rupture-prone plaques, whereas the other lesion types represent stable ones. METHODS: Eighty-three consecutive patients (45 male (54.2%); age 54-88 years (mean 73.2 years)) presenting with an asymptomatic carotid stenosis of 50-99% according to ECST-criteria were recruited. Patients were imaged with a 1.5-T scanner. T1-, T2-, time-of-flight-, and proton-density weighted studies were performed. The carotid plaques were classified as lesion type I-VIII. Clinical endpoints were ischemic stroke, TIA or amaurosis fugax. Survival analysis and log rank test were used to ascertain statistical significance. RESULTS: Six out of 83 patients (7.2%) were excluded: 4 patients had insufficient MR image quality; 1 patient was lost-to-follow-up; 1 patient died shortly after the baseline MRI plaque imaging. The following results were obtained by analyzing the remaining 77 patients. The mean time of follow-up was 41.1 months. During follow-up, n = 9 (11.7%) ipsilateral ischemic cerebrovascular events occurred. Only patients presenting with the high-risk lesion types IV-V and VI developed an ipsilateral cerebrovascular event versus none of the patients presenting with the stable lesion types III, VII, and VIII (n = 9 (11.7%) vs. n = 0 (0%) during follow-up). Event-free survival was higher among patients with the MRI-defined stable lesion types (III, VII, and VIII) than in patients with the high-risk lesion types (IV-V and VI) (log rank test P<0.0001). CONCLUSIONS: MRI plaque imaging has the potential to identify patients with asymptomatic carotid stenosis who are particularly at risk of developing future cerebral ischemia. MRI could improve selection criteria for invasive therapy in the future

CD133⁺ progenitor cells in patients with acute cerebral infarction.

<p>Boxplot demonstrating the number of CD133⁺ progenitor cells (cells/µl) in patients with acute cerebral infarction on day 1 (within 24 hours after symptom onset) and on day 5.</p