309 research outputs found
The rationale for heart team decision-making for patients with stable, complex coronary artery disease
Stable complex coronary artery disease can be treated with coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Multidisciplinary decision-making has gained more emphasis over the recent years to select the most optimal treatment strategy for individual patients with stable complex coronary artery disease. However, the so-called 'Heart Team' concept has not been widely implemented. Yet, decision-making has shown to remain suboptimal; there is large variability in PCI-to-CABG ratios, which may predominantly be the consequence of physician-related factors that have raised concerns regarding overuse, underuse, and inappropriate selection of revascularization. In this review, we summarize these and additional data to support the statement that a multidisciplinary Heart Team consisting of at least a clinical/non-invasive cardiologist, interventional cardiologist, and cardiac surgeon, can together better analyse and interpret the available diagnostic evidence, put into context the clinical condition of the patient as well as consider individual preference and local expertise, and through shared decision-making with the patient can arrive at a most optimal joint treatment strategy recommendation for patients with stable co
Manganites at Quarter Filling: Role of Jahn-Teller Interactions
We have analyzed different correlation functions in a realistic spin-orbital
model for half-doped manganites. Using a finite-temperature diagonalization
technique the CE phase was found in the charge-ordered phase in the case of
small antiferromagnetic interactions between electrons. It is shown
that a key ingredient responsible for stabilization of the CE-type spin and
orbital-ordered state is the cooperative Jahn-Teller (JT) interaction between
next-nearest Mn neighbors mediated by the breathing mode distortion of
Mn octahedra and displacements of Mn ions. The topological phase
factor in the Mn-Mn hopping leading to gap formation in one-dimensional models
for the CE phase as well as the nearest neighbor JT coupling are not able to
produce the zigzag chains typical for the CE phase in our model.Comment: 16 pages with 16 figures, contains a more detailed parameter estimate
based on the structural data by Radaelli et al. (accepted for publication in
Phys. Rev. B
Antithrombotic drug removal from whole blood using Haemoadsorption with a porous polymer bead sorbent
Aim
To evaluate the ability of the DrugSorb™-AntiThrombotic Removal (ATR) haemoadsorption device utilizing porous polymer bead sorbent technology to remove three commonly used antithrombotic drugs from whole blood.
Methods and results
We evaluated the removal of apixaban, rivaroxaban, and ticagrelor by the DrugSorb-ATR haemoadsorption device in a benchtop clinical scale model using bovine whole blood. Blood spiked at clinically relevant concentrations of an antithrombotic agent was continuously circulated through a 300-mL DrugSorb-ATR haemoadsorption device at a flow rate of 300 mL/min. Drug concentration was monitored over 6 h to evaluate drug removal. Results were compared with a control circuit without the haemoadsorption device. Removal rates at 30, 60, 120, and 360 minutes were: apixaban: 81.5%, 96.3%, 99.3% >99.8%; rivaroxaban: 80.7%, 95.1%, 98.9%, >99.5%; ticagrelor: 62.5%; 75%, 86.6%, >95% (all P <0.0001 vs. control). Blood pH and haematological parameters were not significantly affected by the DrugSorb-ATR haemoadsorption device when compared with the control circuit.
Conclusion
DrugSorb-ATR efficiently removes apixaban, rivaroxaban, and ticagrelor in a clinical-scale benchtop recirculation circuit with the bulk of removal occurring in the first 60 minutes. The clinical implications of these findings are currently investigated in patients undergoing on-pump cardiothoracic surgery in two US pivotal trials (ClinicalTrials.gov Identifiers: NCT04976530 and NCT05093504)
The First Magnetic Fields
We review current ideas on the origin of galactic and extragalactic magnetic
fields. We begin by summarizing observations of magnetic fields at cosmological
redshifts and on cosmological scales. These observations translate into
constraints on the strength and scale magnetic fields must have during the
early stages of galaxy formation in order to seed the galactic dynamo. We
examine mechanisms for the generation of magnetic fields that operate prior
during inflation and during subsequent phase transitions such as electroweak
symmetry breaking and the quark-hadron phase transition. The implications of
strong primordial magnetic fields for the reionization epoch as well as the
first generation of stars is discussed in detail. The exotic, early-Universe
mechanisms are contrasted with astrophysical processes that generate fields
after recombination. For example, a Biermann-type battery can operate in a
proto-galaxy during the early stages of structure formation. Moreover, magnetic
fields in either an early generation of stars or active galactic nuclei can be
dispersed into the intergalactic medium.Comment: Accepted for publication in Space Science Reviews. Pdf can be also
downloaded from http://canopus.cnu.ac.kr/ryu/cosmic-mag1.pd
Fetal-derived adrenomedullin mediates the innate immune milieu of the placenta
The remodeling of maternal uterine spiral arteries (SAs) is an essential process for ensuring low-resistance, high-capacitance blood flow to the growing fetus. Failure of SAs to remodel is causally associated with preeclampsia, a common and life-threatening complication of pregnancy that is harmful to both mother and fetus. Here, using both loss-of-function and gain-of-function genetic mouse models, we show that expression of the pregnancy-related peptide adrenomedullin (AM) by fetal trophoblast cells is necessary and sufficient to promote appropriate recruitment and activation of maternal uterine NK (uNK) cells to the placenta and ultimately facilitate remodeling of maternal SAs. Placentas that lacked either AM or its receptor exhibited reduced fetal vessel branching in the labyrinth, failed SA remodeling and reendothelialization, and markedly reduced numbers of maternal uNK cells. In contrast, overexpression of AM caused a reversal of these phenotypes with a concomitant increase in uNK cell content in vivo. Moreover, AM dose-dependently stimulated the secretion of numerous chemokines, cytokines, and MMPs from uNK cells, which in turn induced VSMC apoptosis. These data identify an essential function for fetal-derived factors in the maternal vascular adaptation to pregnancy and underscore the importance of exploring AM as a biomarker and therapeutic agent for preeclampsia
Observation of Orbitally Excited B_s Mesons
We report the first observation of two narrow resonances consistent with
states of orbitally excited (L=1) B_s mesons using 1 fb^{-1} of ppbar
collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the
Fermilab Tevatron. We use two-body decays into K^- and B^+ mesons reconstructed
as B^+ \to J/\psi K^+, J/\psi \to \mu^+ \mu^- or B^+ \to \bar{D}^0 \pi^+,
\bar{D}^0 \to K^+ \pi^-. We deduce the masses of the two states to be m(B_{s1})
= 5829.4 +- 0.7 MeV/c^2 and m(B_{s2}^*) = 5839.7 +- 0.7 MeV/c^2.Comment: Version accepted and published by Phys. Rev. Let
Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research
AIMS The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research.METHODS AND RESULTS Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing & nbsp;definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs.CONCLUSIONS Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.Cardiolog
Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research
Aims The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research.Methods and results Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs.Conclusions Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.Cardiolog
Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn's Disease in Treatment-Naive Pediatric Patients
Background & Aims There is controversy regarding the role of the type 2 immune response in the pathogenesis of ulcerative colitis (UC)?few data are available from treatment-naive patients. We investigated whether genes associated with a type 2 immune response in the intestinal mucosa are up-regulated in treatment-naive pediatric patients with UC compared with patients with Crohn's disease (CD)-associated colitis or without inflammatory bowel disease (IBD), and whether expression levels are associated with clinical outcomes. Methods We used a real-time reverse-transcription quantitative polymerase chain reaction array to analyze messenger RNA (mRNA) expression patterns in rectal mucosal samples from 138 treatment-naive pediatric patients with IBD and macroscopic rectal disease, as well as those from 49 children without IBD (controls), enrolled in a multicenter prospective observational study from 2008 to 2012. Results were validated in real-time reverse-transcription quantitative polymerase chain reaction analyses of rectal RNA from an independent cohort of 34 pediatric patients with IBD and macroscopic rectal disease and 17 controls from Cincinnati Children's Hospital Medical Center. Results We measured significant increases in mRNAs associated with a type 2 immune response (interleukin [IL]5 gene, IL13, and IL13RA2) and a type 17 immune response (IL17A and IL23) in mucosal samples from patients with UC compared with patients with colon-only CD. In a regression model, increased expression of IL5 and IL17A mRNAs distinguished patients with UC from patients with colon-only CD (P =.001; area under the receiver operating characteristic curve, 0.72). We identified a gene expression pattern in rectal tissues of patients with UC, characterized by detection of IL13 mRNA, that predicted clinical response to therapy after 6 months (odds ratio [OR], 6.469; 95% confidence interval [CI], 1.553?26.94), clinical response after 12 months (OR, 6.125; 95% CI, 1.330?28.22), and remission after 12 months (OR, 5.333; 95% CI, 1.132?25.12). Conclusions In an analysis of rectal tissues from treatment-naive pediatric patients with IBD, we observed activation of a type 2 immune response during the early course of UC. We were able to distinguish patients with UC from those with colon-only CD based on increased mucosal expression of genes that mediate type 2 and type 17 immune responses. Increased expression at diagnosis of genes that mediate a type 2 immune response is associated with response to therapy and remission in pediatric patients with UC
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