Catheter directed thrombolytic therapy and aspiration thrombectomy in intermediate pulmonary embolism with long term results

Background: Catheter directed thrombolysis (CDT) and thrombectomy represent well established techniques for the treatment of intermediate pulmonary embolism (IPE). The long-term effect of catheterdirected thrombolysis of IPE is unknown.Methods: Clinical, interventional and echocardiographic data from 80 consecutive patients with IPE who were treated with CDT were evaluated. Primary end-points were technical success and major adverse events. Secondary end-points were cardiovascular mortality, all-cause mortality, clinical success, rate of bleeding complications, improvement in pulmonary pressure and echocardiography parameters. CDT completed with alteplase (10 mg bolus and 1 mg/h maintenance dose) through a pig-tail catheter for 24 h. After 24 h, control pulmonary angiography was performed. Results: In total, 80 patients with a mean age of 59.0 ± 16.8 years were treated. CDT was successful after the first post-operative day in 72 (90%) patients, but thrombus aspiration and fragmentation was performed due to failed thrombolysis in 8 (10%) patients. Final technical and clinical success was reached in 79 (98.8%) and 77 (96.3%) patients, respectively. The mean CDT time in IPE was 27.8 ± 9.6 h. Invasive pulmonary pressure dropped from 57.5 ± 16.7 to 38.9 ± 13.5 (p < 0.001). A caval filter was implanted in 4 (5%) patients. The 1-year major adverse events and cardiovascular mortality rate was 4.0% and 1.4%, respectively. Access site complications (6 major and 6 minor) were encountered in 12 (16.2%) patients.Conclusions: Catheter directed thrombolysis in submassive pulmonary embolism had excellent results. However, additional mechanical thrombectomy was necessary in some patients to achieve good clinical outcomes

Catheter directed thrombolytic therapy and aspiration thrombectomy in intermediate pulmonary embolism with long term results

BACKGROUND: Catheter directed thrombolysis (CDT) and thrombectomy represent well established techniques for the treatment of intermediate pulmonary embolism (IPE). The long-term effect of catheter directed thrombolysis of IPE is unknown. METHODS: Clinical, interventional and echocardiographic data from 80 consecutive patients with IPE who were treated with CDT were evaluated. Primary end-points were technical success and major adverse events. Secondary end-points were cardiovascular mortality, all-cause mortality, clinical success, rate of bleeding complications, improvement in pulmonary pressure and echocardiography parameters. CDT completed with alteplase (10 mg bolus and 1 mg/h maintenance dose) through a pig-tail catheter for 24 h. After 24 h, control pulmonary angiography was performed. RESULTS: In total, 80 patients with a mean age of 59.0 ± 16.8 years were treated. CDT was successful after the first post-operative day in 72 (90%) patients, but thrombus aspiration and fragmentation was performed due to failed thrombolysis in 8 (10%) patients. Final technical and clinical success was reached in 79 (98.8%) and 77 (96.3%) patients, respectively. The mean CDT time in IPE was 27.8 ± 9.6 h. Invasive pulmonary pressure dropped from 57.5 ± 16.7 to 38.9 ± 13.5 (p < 0.001). A caval filter was implanted in 4 (5%) patients. The 1-year major adverse events and cardiovascular mortality rate was 4.0% and 1.4%, respectively. Access site complications (6 major and 6 minor) were encountered in 12 (16.2%) patients. CONCLUSIONS: Catheter directed thrombolysis in submassive pulmonary embolism had excellent results. However, additional mechanical thrombectomy was necessary in some patients to achieve good clinical outcomes

Risk factors for cognitive dysfunction amongst patients with cardiovascular diseases

BackgroundThe impact of cardiovascular diseases on cognition raises important research questions. The study aimed to investigate the relationship between demographic data, cardiovascular diseases, kidney disease and depressive symptoms on cognition.MethodsA cross-sectional study of patients with cardiovascular diseases was performed. The Montreal Cognitive Assessment (MoCA) was applied for cognitive evaluation. Based on MoCA three groups were defined: preserved cognition, mild, and advanced cognitive dysfunction (CD). Data were analyzed using Cronbach alpha (Cα) and McDonald’s ω (Mω) for internal consistency. The Chi-square test, Cramer’s V test, and correlation analyses were also applied.ResultsOf 628 patients, 55.2% had mild CD, and the mean age was 67.95 (SD 9.53) years. Cα and Mω were 0.7, indicating good internal consistency. We found a moderate positive correlation between depression and the severity of CD (r = 0.25, p = 0.0001). A weak association between CD and female gender (p = 0.016), atrial fibrillation (p = 0.03), stroke (p = 0.009), and a moderate association for age group (p &lt; 0.0001), education level (p &lt; 0.0001), smoking (p &lt; 0.0001), and renal dysfunction (p &lt; 0.0001) was found. Age ≥ 70 years, eGFR 30–59 mL/min/1.73m2 significantly increased the likelihood for mild and advanced CD, while smoking and &gt; 9 classes decreased it. Female gender, history of atrial fibrillation, and stroke significantly increased the likelihood of advanced CD.ConclusionMild CD was the most common in patients with cardiovascular diseases. Older age, lower education, being a non-smoker, and renal dysfunction were risk factors for both mild and advanced CD. Female gender, previous diagnosis of atrial fibrillation, and stroke are risk factors for advanced CD

Elucidation of the binding mode of organic polysulfides on the human TRPA1 receptor

Introduction: Previous studies have established that endogenous inorganic polysulfides have significant biological actions activating the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor. Organic polysulfides exert similar effects, but they are much more stable molecules, therefore these compounds are more suitable as drugs. In this study, we aimed to better understand the mechanism of action of organic polysulfides by identification of their binding site on the TRPA1 receptor.Methods: Polysulfides can readily interact with the thiol side chain of the cysteine residues of the protein. To investigate their role in the TRPA1 activation, we replaced several cysteine residues by alanine via site-directed mutagenesis. We searched for TRPA1 mutant variants with decreased or lost activating effect of the polysulfides, but with other functions remaining intact (such as the effects of non-electrophilic agonists and antagonists). The binding properties of the mutant receptors were analyzed by in silico molecular docking. Functional changes were tested by in vitro methods: calcium sensitive fluorescent flow cytometry, whole-cell patch-clamp and radioactive calcium-45 liquid scintillation counting.Results: The cysteines forming the conventional binding site of electrophilic agonists, namely C621, C641 and C665 also bind the organic polysulfides, with the key role of C621. However, only their combined mutation abolished completely the organic polysulfide-induced activation of the receptor.Discussion: Since previous papers provided evidence that organic polysulfides exert analgesic and anti-inflammatory actions in different in vivo animal models, we anticipate that the development of TRPA1-targeted, organic polysulfide-based drugs will be promoted by this identification of the binding site

Carboxypeptidase-M is regulated by lipids and CSFs in macrophages and dendritic cells and expressed selectively in tissue granulomas and foam cells

Granulomatous inflammations, characterized by the presence of activated macrophages (MAs) forming epithelioid cell (EPC) clusters, are usually easy to recognize. However, in ambiguous cases the use of a MA marker that expresses selectively in EPCs may be needed. Here, we report that carboxypeptidase-M (CPM), a MA-differentiation marker, is preferentially induced in EPCs of all granuloma types studied, but not in resting MAs. As CPM is not expressed constitutively in MAs, this allows utilization of CPM-immunohistochemistry in diagnostics of minute granuloma detection when dense non-granulomatous MAs are also present. Despite this rule, hardly any detectable CPM was found in advanced/active tubercle caseous disease, albeit in early tuberculosis granuloma, MAs still expressed CPM. Indeed, in vitro both the CPM-protein and -mRNA became downregulated when MAs were infected with live mycobacteria. In vitro, MA-CPM transcript is neither induced remarkably by interferon-γ, known to cause classical MA activation, nor by IL-4, an alternative MA activator. Instead, CPM is selectively expressed in lipid-laden MAs, including the foam cells of atherosclerotic plaques, xanthomatous lesions and lipid pneumonias. By using serum, rich in lipids, and low-density lipoprotein (LDL) or VLDL, CPM upregulation could be reproduced in vitro in monocyte-derived MAs both at transcriptional and protein levels, and the increase is repressed under lipid-depleted conditions. The microarray analyses support the notion that CPM induction correlates with a robust progressive increase in CPM gene expression during monocyte to MA maturation and dendritic cell (DC) differentiation mediated by granulocyte–MA-colony-stimulating factor+IL-4. M-CSF alone also induced CPM. These results collectively indicate that CPM upregulation in MAs is preferentially associated with increased lipid uptake, and exposure to CSF, features of EPCs, also. Therefore, CPM-immunohistochemistry is useful for granuloma and foam MA detections in tissue sections. Furthermore, the present data offer CPM for the first time to be a novel marker and cellular player in lipid uptake and/or metabolism of MAs by promoting foam cell formation

Development and validation of HERWIG 7 tunes from CMS underlying-event measurements

This paper presents new sets of parameters (“tunes”) for the underlying-event model of the HERWIG7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in HERWIG7, and are obtained from a fit to minimum-bias data collected by the CMS experiment at s=0.9, 7, and 13Te. The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the dat

Search for top squark pair production using dilepton final states in pp collision data collected at root s=13TeV

A search is presented for supersymmetric partners of the top quark (top squarks) in final states with two oppositely charged leptons (electrons or muons), jets identified as originating from bquarks, and missing transverse momentum. The search uses data from proton-proton collisions at root s = 13 TeV collected with the CMS detector, corresponding to an integrated luminosity of 137 fb(-1). Hypothetical signal events are efficiently separated from the dominant top quark pair production background with requirements on the significance of the missing transverse momentum and on transverse mass variables. No significant deviation is observed from the expected background. Exclusion limits are set in the context of simplified supersymmetric models with pair-produced lightest top squarks. For top squarks decaying exclusively to a top quark and a lightest neutralino, lower limits are placed at 95% confidence level on the masses of the top squark and the neutralino up to 925 and 450 GeV, respectively. If the decay proceeds via an intermediate chargino, the corresponding lower limits on the mass of the lightest top squark are set up to 850 GeV for neutralino masses below 420 GeV. For top squarks undergoing a cascade decay through charginos and sleptons, the mass limits reach up to 1.4 TeV and 900 GeV respectively for the top squark and the lightest neutralino.Peer reviewe

Measurement of the t(t)over-barb(b)over-bar production cross section in the all-jet final state in pp collisions at root s=13 TeV

A measurement of the production cross section of top quark pairs in association with two b jets (t (t) over barb (b) over bar) is presented using data collected in proton-proton collisions at root s=13 TeV by the CMS detector at the LHC corresponding to an integrated luminosity of 35.9 fb(-1). The cross section is measured in the all-jet decay channel of the top quark pair by selecting events containing at least eight jets, of which at least two are identified as originating from the hadronization of b quarks. A combination of multivariate analysis techniques is used to reduce the large background from multijet events not containing a top quark pair, and to help discriminate between jets originating from top quark decays and other additional jets. The cross section is determined for the total phase space to be 5.5 +/- 0.3 (stat)(-1.3)(+)(1.6) (syst)pb and also measured for two fiducial t (t) over barb (b) over bar, definitions. The measured cross sections are found to be larger than theoretical predictions by a factor of 1.5-2.4, corresponding to 1-2 standard deviations. (C) 2020 The Author. Published by Elsevier B.V.Peer reviewe

Measurement of the W gamma Production Cross Section in Proton-Proton Collisions at root s=13 TeV and Constraints on Effective Field Theory Coefficients

A fiducial cross section for W gamma production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb(-1) of data collected using the CMS detector at the LHC. The W -> e nu and mu nu decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.Peer reviewe

Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at root s(NN)=5.02 TeV

The second-order Fourier coefficients (v(2)) characterizing the azimuthal distributions of Y(1S) and Y(2S) mesons produced in PbPb collisions at root s(NN) = 5.02 TeV are studied. The Y mesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb(-1). The scalar product method is used to extract the v2 coefficients of the azimuthal distributions. Results are reported for the rapidity range vertical bar y vertical bar < 2.4, in the transverse momentum interval 0 < pT < 50 GeV/c, and in three centrality ranges of 10-30%, 30-50% and 50-90%. In contrast to the J/psi mesons, the measured v(2) values for the Y mesons are found to be consistent with zero. (C) 2021 The Author(s). Published by Elsevier B.V.Peer reviewe