Background
In several settings, a shorter time to diagnosis has been shown to lead to improved clinical outcomes. The implementation of a rapid laboratory testing allows for a pre-visit testing in ...the outpatient clinic, meaning that test results are available during the first outpatient visit.
Objective
To determine whether the pre-visit laboratory testing leads to a shorter time to diagnosis in the general internal medicine outpatient clinic.
Design
An “on-off” trial, allocating subjects to one of two treatment arms in consecutive alternating blocks.
Participants
All new referrals to the internal medicine outpatient clinic of a university hospital were included, excluding second opinions. A total of 595 patients were eligible; one person declined to participate, leaving data from 594 patients for analysis.
Intervention
In the intervention group, patients had a standardized pre-visit laboratory testing before the first visit.
Main Measures
The primary outcome was the time to diagnosis. Secondary outcomes were the correctness of the preliminary diagnosis on the first day, health care utilization, and patient and physician satisfaction.
Key Results
There was no difference in time to diagnosis between the two groups (median 35 days vs 35 days; hazard ratio 1.03 0.87–1.22;
p
= .71). The pre-visit testing group had higher proportions of both correct preliminary diagnoses on day 1 (24% vs 14%;
p
= .003) and diagnostic workups being completed on day 1 (10% vs 3%;
p
< .001). The intervention group had more laboratory tests done (50.0 interquartile range (IQR) 39.0–69.0 vs 43.0 IQR 31.0–68.5;
p
< .001). Otherwise, there were no differences between the groups.
Conclusions
Pre-visit testing did not lead to a shorter overall time to diagnosis. However, a greater proportion of patients had a correct diagnosis on the first day. Further studies should focus on customizing pre-visit laboratory panels, to improve their efficacy.
Trial Registration
NL5009
Diffuse brain infiltration by glioma cells causes detrimental disease progression, but its multicellular coordination is poorly understood. We show here that glioma cells infiltrate the brain ...collectively as multicellular networks. Contacts between moving glioma cells are adaptive epithelial-like or filamentous junctions stabilized by N-cadherin, β-catenin and p120-catenin, which undergo kinetic turnover, transmit intercellular calcium transients and mediate directional persistence. Downregulation of p120-catenin compromises cell-cell interaction and communication, disrupts collective networks, and both the cadherin and RhoA binding domains of p120-catenin are required for network formation and migration. Deregulating p120-catenin further prevents diffuse glioma cell infiltration of the mouse brain with marginalized microlesions as the outcome. Transcriptomics analysis has identified p120-catenin as an upstream regulator of neurogenesis and cell cycle pathways and a predictor of poor clinical outcome in glioma patients. Collective glioma networks infiltrating the brain thus depend on adherens junctions dynamics, the targeting of which may offer an unanticipated strategy to halt glioma progression.
Abstract
Background
Patients who underwent carotid endarterectomy (CEA) still have a residual risk of 13% of developing a major adverse cardiovascular event (MACE) within 3 years. Inflammatory ...processes leading up to MACE are not fully understood. Therefore, we examined blood cell characteristics (BCCs), possibly reflecting inflammatory processes, in relation to MACE to identify BCCs that may contribute to an increased risk.
Methods
We analyzed 75 pretreatment BCCs from the Sapphire analyzer, and clinical data from the AtheroExpress biobank in relation to MACE after CEA using Random Survival Forests, and a Generalized Additive Survival Model. To understand biological mechanisms, we related the identified variables to intraplaque hemorrhage (IPH).
Results
Of 783 patients, 97 (12%) developed MACE within 3 years after CEA. Red blood cell distribution width (RDW) (HR 1.23 1.02, 1.68, p = 0.022), CV of lymphocyte size (LACV) (HR 0.78 0.63, 0.99, p = 0.043), neutrophil complexity of the intracellular structure (NIMN) (HR 0.80 0.64, 0.98, p = 0.033), mean neutrophil size (NAMN) (HR 0.67 0.55, 0.83, p < 0.001), mean corpuscular volume (MCV) (HR 1.35 1.09, 1.66, p = 0.005), eGFR (HR 0.65 0.52, 0.80, p < 0.001); and HDL (HR 0.62 0.45, 0.85, p = 0.003) were related to MACE. NAMN was related to IPH (OR 0.83 0.71 - 0.98, p = 0.02).
Conclusions
This is the first study to present a higher RDW and MCV and lower LACV, NIMN and NAMN as biomarkers reflecting inflammatory processes that may contribute to an increased risk of MACE after CEA.Variables associated with secondary MACE
Abstract
Introduction
The success of endovascular thrombectomy (EVT) in acute ischemic stroke is related to stroke etiology and clot composition. The latter two may differ between women and men. An ...improved understanding of sex differences in EVT success may contribute to more personalized treatment. We therefore tested the hypothesis that blood cell characteristics (BCCs) related to EVT success in acute ischemic stroke differ by sex.
Methods
We analyzed electronic health record (EHR) data of AIS patients undergoing EVT at a single intervention center. Of 311 patients, 71 pretreatment erythrocyte-, leukocyte-, and thrombocyte-related BCCs from the Sapphire hematology analyzer were extracted. BCCs were sex-stratified, clustered, and analyzed based on the first principal component of the clusters. To identify BCC clusters related to successful EVT (TICI 3), Partial Least Squares Discriminant Analysis (sPLS-DA) was performed, including cross-validation and stability selection to identify stable BCCs relative to EVT success in women and men. We also related the identified BCCs to stroke etiology (cardioembolism (CE), large-artery atherosclerosis (LAA), undetermined), and controlled for known cardiovascular risk factors.
Results
Successful EVT was achieved in 69 women (51%) and 87 men (49%). Women and men differed on 21 out of 71 BCCs (pFDR-corrected < 0.05). Analyzing sex-stratified data led to lower error rates for the female model for EVT success compared to the pooled (t(192.4) = 5.9, p < 0.001), and male model (t(182.6) = -15.6, p < 0.001). In women, a higher number of reticulocytes was associated with successful EVT and CE, whereas a higher mean corpuscular hemoglobin concentration was associated with unsuccessful EVT and LAA. In men, a higher coefficient of variance of lymphocyte complexity of the intracellular structure was associated unsuccessful EVT and LAA.
Conclusions
BCCs associated with EVT success differed by sex and were related to stroke subtype. This improved understanding may contribute to more personalized treatment of acute ischemic stroke.Model performance after sex-stratifyingSex-specific BCCs relate to EVT success
The ratio R(f0/phi) of the branching fractions of the B0,s meson to the CP-odd eigenstate J/psi f0(980) and to J/psi phi(1020) is measured, where J/psi to mu+ mu-, f0 to pi+ pi-, and phi to K+ K-. ...The analysis is based on a data sample of pp collisions at a centre-of-mass energy of 7 TeV, collected by the CMS experiment, corresponding to an integrated luminosity of 5.3 inverse femtobarns. The result is R(f0/phi) = 0.140 +/- 0.013 +/- 0.018, where the first uncertainty is statistical and the second is systematic. This result is consistent with theoretical predictions and previous measurements of R(f0/phi). It is the most precise measurement of the ratio to date.
A measurement of inclusive ZZ production cross section and constraints on anomalous triple gauge couplings in proton-proton collisions at sqrt(s) = 8 TeV are presented. A data sample, corresponding ...to an integrated luminosity of 19.6 inverse femtobarns was collected with the CMS experiment at the LHC. The measurements are performed in the leptonic decay modes ZZ to lll'l', where l = e, mu and l' = e, mu, tau. The measured total cross section, sigma(pp to ZZ) = 7.7 +/- 0.5 (stat.) +0.5-0.4 (syst.) +/- 0.4 (theo.) +/- 0.2 (lum.) pb for both Z bosons produced in the mass range 60 < mZ < 120 GeV, is consistent with standard model predictions. Differential cross sections are measured and well described by the theoretical predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ gamma couplings at the 95% confidence level: -0.004
The first measurement of the cross section ratio sigma(t t-bar b b-bar) / sigma(t t-bar jj) is presented using a data sample corresponding to an integrated luminosity of 19.6 inverse femtobarns ...collected in pp collisions at sqrt(s) = 8 TeV with the CMS detector at the LHC. Events with two leptons (e or mu) and four reconstructed jets, including two identified as b quark jets, in the final state are selected. The ratio is determined for a minimum jet transverse momentum pt of both 20 and 40 GeV. The measured ratio is 0.022 +/- 0.003 (stat) +/- 0.005 (syst) for pt > 20 GeV. The absolute cross sections sigma(t t-bar b b-bar) and sigma(t t-bar jj) are also measured. The measured ratio for pt > 40 GeV is compatible with a theoretical quantum chromodynamics calculation at next-to-leading order.
Measurements of the five most significant angular coefficients, A0 through A4, for Z bosons produced in pp collisions at sqrt(s)=8 TeV and decaying to mu+mu- are presented as a function of the ...transverse momentum and rapidity of Z boson. The integrated luminosity of the dataset collected with the CMS detector at the LHC corresponds to 19.7 inverse femtobarns. These measurements provide comprehensive information about Z boson production mechanisms, and are compared to QCD predictions at leading order, next-to-leading order, and next-to-next-to-leading order in perturbation theory.
A search is performed for heavy Majorana neutrinos (N) using an event signature defined by two muons of the same charge and two jets (mu+/- mu+/- jj). The data correspond to an integrated luminosity ...of 19.7 inverse femtobarns of proton-proton collisions at a center-of-mass energy of 8 TeV, collected with the CMS detector at the CERN LHC. No excess of events is observed beyond the expected standard model background and upper limits are set on abs(Vmu,N)^2 as a function of Majorana neutrino mass mN for masses in the range of 40-500 GeV, where Vmu,N is the mixing element of the heavy neutrino with the standard model muon neutrino. The limits obtained are abs(Vmu,N)^2 < 0.00470 for mN = 90 GeV, abs(Vmu,N)^2 < 0.0123 for mN = 200 GeV, and abs(Vmu,N)^2 < 0.583 for mN = 500 GeV. These results extend considerably the regions excluded by previous direct searches.