bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Occurrence of Rosai–Dorfman Disease and Nodal Marginal Zone Lymphoma in a Patient with Sjögren’s Syndrome
Authors: Gorodetskiy Vadim R. , Klapper Wolfram , Probatova Natalya A. , Vasilyev Vladimir I. , Rozhnova Elena V.
Published: September 2018

We present an exceptionally rare case of co-occurrence of Rosai–Dorfman disease (RDD) and nodal marginal zone lymphoma (NMZL) in a 60-year-old Caucasian female with a 20-year course of Sjögren’s syndrome (SS). In response to treatment for lymphoma, the patient presented a short positive response, followed by a rapid progression of the disease accompanied by the development of the peripheral facial nerve palsy. We failed to detect Epstein–Barr virus (EBV) in the NMZL/RDD sample by EBV-encoded RNA (EBER) in situ hybridization but identified genomic DNA of EBV by polymerase chain reaction. A second biopsy revealed EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified. The identical clonal immunoglobulin heavy chain gene rearrangements in the NMZL and DLBCL pointed to their clonal relationship. Though the role of EBV in the pathogenesis of some lymphomas is well-known, there have been only few cases of EBV-induced transformation of low-grade B-cell lymphoma into high-grade lymphoma and no cases of a patient with an NMZL background. To our knowledge, this is the first report of a concomitant occurrence of RDD and NMZL in a SS patient.
Highly Efficient Photocatalytic Hydrogen on CoS/TiO2 Photocatalysts from Aqueous Methanol Solution
Authors: Niu Yu , Li Fuying , Yang Kai , Wu Qiyou , Xu Peijing , Wang Renzhang
Published: September 2018

The photocatalyzed water splitting reaction in aqueous methanol solution is an efficient preparation method for hydrogen and methanal under mild conditions. In this work, metal sulfide-loaded TiO2 photocatalysts for hydrogen and methanol production were synthesized by hydrothermal method (180°C/12 h) and characterized by X-ray diffraction (XRD), UV-visible diffuse reflectance spectroscopy (DRS), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). The crystal structures of the samples are the typical anatase phase of TiO2 and exhibit a spherical morphology. When TiO2 was loaded with CoS, ZnS, and Bi2S3, respectively, the resulting catalysts showed photocatalytic activities for water decomposition to hydrogen in aqueous methanol solution under 300 W Xe lamp irradiation. Among the photocatalysts with various compositions, the 20 wt% CoS/TiO2 sample with a 2.1 eV band gap showed the maximum photocatalytic activity for the photocatalytic reaction, which indicated that CoS improved the separation ratio of photoexcited electrons and holes. The enhanced activity can be attributed to the intimate junctions that are formed between CoS and TiO2, which can reduce the electron-hole recombination. The production rate of hydrogen with 20 wt% CoS/TiO2 photocatalyst was about 5.6 mmol/g/h, which was 67 times higher than that of pure TiO2. The formation rate of HCHO was 1.9 mmol/g/h with 98.7% selectivity. Moreover, the CoS/TiO2 photocatalyst demonstrated good reusability and stability. In the present study, it is demonstrated that CoS can act as an effective cocatalyst to enhance the photocatalytic hydrogen and methanal production activity of TiO2. The highly improved performance of the CoS/TiO2 composite was mainly ascribed to the efficient charge separation.
A Framework for Visualizing Heterogeneous Construction Data Using Semantic Web Standards
Authors: Ali Mostafa , Mohamed Yasser
Published: September 2018

3D Visualization provides a mean for communicating different construction activities to diverse audiences. The scope, level of detail, and time resolution of the 3D visualization process are determined based on the targeted audiences. Developing the 3D visualization requires obtaining and merging heterogeneous data from different sources (such as BIM model and CPM schedule). The data merging process is usually carried out on ad hoc basis for a specific visualization case which limits the reusability of the process. This paper discusses a framework for automatic merging of heterogeneous data to create a visualization. The paper describes developing an ontology which captures concepts related to the visualization process. Then, heterogeneous data sources that are commonly used in construction are fed into the ontology which can be queried to produce different visualization scenarios. The potential of this approach has been demonstrated by providing multiple visualization scenarios that cover different audiences, levels of detail, and time resolutions.
Thyroid Function in Chronically Transfused Children with Beta Thalassemia Major: A Cross-Sectional Hospital Based Study
Authors: Upadya Suraj Haridas , Rukmini M. S. , Sundararajan Sowmya , Baliga B. Shantharam , Kamath Nutan
Published: September 2018

Background.Thalassemia is the most common genetic disorder worldwide. Use of iron chelators has improved survival but endocrine complications have become more frequent. The frequency of hypothyroidism in Beta Thalassemia Major (BTM) children ranges from 6 to 30 %. Thyroid dysfunction mainly occurs by gland infiltration, chronic tissue hypoxia, free radical injury, and organ siderosis.Objectives.(a) To evaluate the thyroid function status in chronically transfused children with BTM, in the first and second decade of life and (b) to study the influence of factors like duration and amount of blood transfusions, serum ferritin level, and iron chelation therapy on thyroid function.Methodology.BTM children, 3 years old and above, on regular blood transfusions with serum ferritin > 1500 mcg/l were included in the study. Thyroid function and ferritin assessment was done using ELISA kits. Autoimmune thyroiditis was ruled out by antithyroid peroxidase and antithyroglobulin antibody testing.Results.A study population of 83 children consisted of 49 boys (59%) and 34 girls (41%). 4.8% of the children had evidence of subclinical hypothyroidism. Among them two belonged to the first decade and the other two to the second decade of life. Mean TSH, FT4, and ferritin values among children with thyroid dysfunction were 6.38 ± 0.83 mIU/ml, 1.08 ± 0.45 ng/dl, and 3983.0±1698.30 ng/ml, respectively. The severity of thyroid dysfunction was statistically significantly associated with higher serum TSH values in children in the second decade of life with a p value = 0.001. No other significant correlation was found between oral chelation, amount and duration of blood transfusion, or serum ferritin levels.Conclusion.Subclinical hypothyroidism was the thyroid dysfunction observed in our study. Regular blood transfusions with adequate chelation may decrease incidence of thyroid dysfunction.
Effect of Chemical Composition on the Nanoscale Ordering Transformations of Physical Mixtures of Pd and Cu Nanoparticles
Authors: Mukundan Vineetha , Shan Shiyao , Zhong Chuan-Jian , Malis Oana
Published: September 2018

The nanoscale composition and structure of alloy catalysts affect their performance in heterogeneous catalysis. In particular, previous reports indicated that PdCu nanoparticles are more efficient as catalysts in fuel cell reactions than monometallic Pd catalysts. To understand the structural transformations of PdCu nanoalloys, real-time in situ synchrotron X-ray diffraction was used to examine the temperature-induced evolution of physical mixtures of Pd and Cu nanoparticles. Ex situ transmission electron microscopy measurements provide additional information about the size, phase, composition, and ordering of the nanoparticle mixtures. The results for PdCu mixtures of composition 1 : 1 and 3 : 1 supported on SiO2 are presented in detail here. The annealing procedure involved two stages: (a) isothermal annealing at 450°C and (b) ramped annealing from 450°C to 750°C, both in forming gas atmospheres. We found the ordered B2 phase to be formed at 450°C in all compositions studied. Ramped annealing of PdCu 1 : 1 mixtures from 450°C to 750°C leads to the transformation of the B2 phase into two different alloys, one rich in Cu and the other rich in Pd. This structural evolution bears the signature of spinodal decomposition and is different from that of PdCu bulk alloys. In PdCu 3 : 1 mixtures, the B2 phase dominates after isothermal annealing at 450°C, but a significant disordered alloy fcc phase is also formed. During annealing at 750°C, the disordered fcc phase grows at the expense of the B2 phase. These findings are important for the understanding of thermal activation of PdCu nanocatalysts for fuel cells.
Failure Depth of a Floor of a Fully Mechanized Working Face When Passing a Collapse Column
Authors: Cai Jinlong , Tu Min , Xu Wensong
Published: September 2018

The stress change law of a collapse column and the failure depth of a coal seam floor before and after mining when the fully mechanized coal mining face passes through the collapse column are investigated. Here, we present the constructed program in FISH language, render the damage variable in FLAC3D to establish the numerical model, and complete the numerical calculation. The 10–115 working faces that pass the collapse column at a coal mine in Tuanbai are identified as the research object. The floor failure is numerically simulated to assess the damage. The following results were obtained: the failure depth of the full floor is stabilized at 14.6 m; the maximum failure depth of the floor near the collapse column is 18.2 m; and the stress concentration coefficient is 1.27 times greater than that of normal mining. The calculated depth failure of the floor of the working face without structural defects is 14.6–14.7 m based on the Hoek–Brown criterion. With the collapse column, the failure depth of the floor is 16.8–17.8 m. According to the water injection test, the maximum failure depth of the floor is 18 m. The three derived values agree well with one another.
Distinct Clinical Factors in Hospitalized Patients with Diverticular Bleeding and Diverticulitis
Authors: Urabe Makiko , Nishida Tsutomu , Shimakoshi Hiromi , Shimoda Akiyoshi , Amano Takahiro , Sugimoto Aya , Takahashi Kei , Mukai Kaori , Matsubara Tokuhiro , Yamamoto Masashi , Hayashi Shiro , Nakajima Sachiko , Fukui Koji , Tanida Tsukasa , Komori Takamichi , Morita Shunji , Inada Masami
Published: September 2018

Background/Aims: It is unclear why colonic diverticular bleeding and diverticulitis rarely coexist. This study compared the characteristics of these conditions. Methods: This single-center retrospective study examined 310 consecutive patients hospitalized with an episode of diverticular disease (cases) and outpatients without a diverticular episode (controls) from January 2012 to December 2015. We investigated distinct clinical factors in hospitalized patients with diverticular bleeding and diverticulitis. Results: We identified 183 patients with 263 episodes of diverticular bleeding and 127 patients with 135 episodes of diverticulitis during the study period. Patients with diverticular bleeding were significantly older than those with diverticulitis (median age 76 vs. 56 years) and had more cardiovascular disease, hypertension, diabetes, cerebrovascular disease, chronic kidney disease, lipid disorder, or a poorer performance status. Significantly more diverticular bleeding patients were taking antiplatelet drugs, anticoagulant drugs, proton pump inhibitors, or laxative agents. Multivariate analysis revealed that an age > 65 years (OR 5.42), and antiplatelet agent use (OR 7.29) were more significant risk factors for diverticular bleeding than for diverticulitis. Conclusions: Elderly people using antiplatelet drugs may be more susceptible to diverticular bleeding than diverticulitis.
Serum Lipopolysaccharide-Binding Protein is Associated with Chronic Inflammation and Metabolic Syndrome in Hemodialysis Patients
Authors: Lim Paik Seong , Chang Yu-Kang , Wu Tsai-Kun
Published: September 2018

Background: In hemodialysis (HD) patients, impaired gut barrier and alteration in microbiota in the gut is thought to increase the risk of bacterial translocation and chronic inflammation. Lipopolysaccharide-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by microbial products. Our aim is to investigate the relationship between circulating levels of LBP, and various metabolic and inflammatory markers in HD patients. Besides, we also aim to determine its relationship among ­patients with different body mass index. Patients and Methods: A total of 123 HD patients were stratified into three ­tertiles, according to serum LBP level. The LBP and inflammatory markers were determined using immunoassay methods. A bioimpedance spectroscopy device was used for body composition measurement. Results: The serum levels of the two proinflammatory markers, high-sensitivity C-reactive protein (hsCRP) and interleukin (IL)-6, were significantly higher in patients in the upper tertile when compared with the rest of the tertiles. In HD patients, a significant positive correlation was found between serum LBP levels and CRP, IL-6, soluble CD14 (sCD14), and fasting blood glucose levels. Patients with metabolic syndrome and pre-existing cardiovascular disease had higher LBP levels than those without metabolic syndrome. Besides, obese patients were also associated with higher serum LBP levels. Multivariate regression analyses showed that IL-6 level was the strongest correlate of LBP level, followed by hsCRP level and sCD14. Conclusions: Our study suggested that elevated plasma LBP was associated with metabolic syndrome and obesity. In addition, increased LBP level was correlated positively to markers of inflammation, and sCD14 levels.
Epigenetic Regulation of Endothelial-to-Mesenchymal Transition in Chronic Heart Disease
Authors: Hulshoff Melanie S. , Xu Xingbo , Krenning Guido , Zeisberg Elisabeth M.
Published: September 2018

Endothelial-to-mesenchymal transition (EndMT) is a process in which endothelial cells lose their properties and transform into fibroblast-like cells. This transition process contributes to cardiac fibrosis, a common feature of patients with chronic heart failure. To date, no specific therapies to halt or reverse cardiac fibrosis are available, so knowledge of the underlying mechanisms of cardiac fibrosis is urgently needed. In addition, EndMT contributes to other cardiovascular pathologies such as atherosclerosis and pulmonary hypertension, but also to cancer and organ fibrosis. Remarkably, the molecular mechanisms driving EndMT are largely unknown. Epigenetics play an important role in regulating gene transcription and translation and have been implicated in the EndMT process. Therefore, epigenetics might be the missing link in unraveling the underlying mechanisms of EndMT. Here, we review the involvement of epigenetic regulators during EndMT in the context of cardiac fibrosis. The role of DNA methylation, histone modifications (acetylation and methylation), and noncoding RNAs (microRNAs, long noncoding RNAs, and circular RNAs) in the facilitation and inhibition of EndMT are discussed, and potential therapeutic epigenetic targets will be highlighted.
BDNF (Brain-Derived Neurotrophic Factor) Promotes Embryonic Stem Cells Differentiation to Endothelial Cells Via a Molecular Pathway, Including MicroRNA-214, EZH2 (Enhancer of Zeste Homolog 2), and eNOS (Endothelial Nitric Oxide Synthase)
Authors: Descamps Betty , Saif Jaimy , Benest Andrew V. , Biglino Giovanni , Bates David O. , Chamorro-Jorganes Aranzazu , Emanueli Costanza
Published: September 2018

Objective—

The NTs (neurotrophins), BDNF (brain-derived neurotrophic factor) and NT-3 promote vascular development and angiogenesis. This study investigated the contribution of endogenous NTs in embryonic stem cell (ESC) vascular differentiation and the potential of exogenous BDNF to improve the process of ESC differentiation to endothelial cells (ECs).

Approach and Results—

Mouse ESCs were differentiated into vascular cells using a 2-dimensional embryoid body (EB) model. Supplementation of either BDNF or NT-3 increased EC progenitors’ abundance at day 7 and enlarged the peripheral vascular plexus with ECs and SM22α
+
(smooth muscle 22 alpha-positive) smooth muscle cells by day 13. Conversely, inhibition of either BDNF or NT-3 receptor signaling reduced ECs, without affecting smooth muscle cells spread. This suggests that during vascular development, endogenous NTs are especially relevant for endothelial differentiation. At mechanistic level, we have identified that BDNF-driven ESC-endothelial differentiation is mediated by a pathway encompassing the transcriptional repressor EZH2 (enhancer of zeste homolog 2), microRNA-214 (miR-214), and eNOS (endothelial nitric oxide synthase). It was known that eNOS, which is needed for endothelial differentiation, can be transcriptionally repressed by EZH2. In turn, miR-214 targets EZH2 for inhibition. We newly found that in ESC-ECs, BDNF increases miR-214 expression, reduces EZH2 occupancy of the
eNOS
promoter, and increases eNOS expression. Moreover, we found that NRP-1 (neuropilin 1), KDR (kinase insert domain receptor), and pCas
130
(p130 Crk-associated substrate kinase), which reportedly induce definitive endothelial differentiation of pluripotent cells, were increased in BDNF-conditioned ESC-EC. Mechanistically, miR-214 mediated the BDNF-induced expressional changes, contributing to BDNF-driven endothelial differentiation. Finally, BDNF-conditioned ESC-ECs promoted angiogenesis in vitro and in vivo.

Conclusions—

BDNF promotes ESC-endothelial differentiation acting via miR-214.
Pharmacological Modulation of Right Ventricular Endocardial-Epicardial Gradients in Brugada Syndrome
Authors: Bhar-Amato Justine , Finlay Malcolm , Santos Diogo , Orini Michele , Chaubey Sanjay , Vyas Vishal , Taggart Peter , Grace Andrew A. , Huang Christopher L.-H. , Ben Simon Ron , Tinker Andrew , Lambiase Pier D.
Published: September 2018

Background

We explored the hypothesis that increased cholinergic tone exerts its proarrhythmic effects in Brugada syndrome (BrS) through increasing dispersion of transmural repolarization in patients with spontaneous and drug-induced BrS.

Methods

BrS and supraventricular tachycardia patients were studied after deploying an Ensite Array in the right ventricular outflow tract and a Cardima catheter in the great cardiac vein to record endo and epicardial signals, respectively. S
1
-S
2
restitution curves from the right ventricular apex were conducted at baseline and after edrophonium challenge to promote increased cholinergic tone. The local unipolar electrograms were then analyzed to study transmural conduction and repolarization dynamics.

Results

The study included 8 BrS patients (5 men:3 women; mean age, 56 years) and 8 controls patients with supraventricular tachycardia (5 men:3 women; mean age, 48 years). Electrophysiological studies in controls demonstrated shorter endocardial than epicardial right ventricular activation times (mean difference: 26 ms;
P
<0.001). In contrast, patients with BrS showed longer endocardial than epicardial activation time (mean difference: −15 ms;
P
=0.001). BrS hearts, compared with controls, showed significantly larger transmural gradients in their activation recovery intervals (mean intervals, 20.5 versus 3.5 ms;
P
<0.01), with longer endocardial than epicardial activation recovery intervals. Edrophonium challenge increased such gradients in both controls (to a mean of 16 ms [
P
<0.001]) and BrS (to 29.7 ms;
P
<0.001). However, these were attributable to epicardial and endocardial activation recovery interval prolongations in control and BrS hearts, respectively. Dynamic changes in repolarization gradients were also observed across the BrS right ventricular wall in BrS.

Conclusions

Differential contributions of conduction and repolarization were identified in BrS which critically modulated transmural dispersion of repolarization with significant cholinergic effects only identified in the patients with BrS. This has important implications for explaining the proarrhythmic effects of increased vagal tone in BrS, as well as evaluating autonomic modulation and epicardial ablation as therapeutic strategies.
Permanent His Bundle Pacing for Cardiac Resynchronization Therapy in Patients With Heart Failure and Right Bundle Branch Block
Authors: Sharma Parikshit S. , Naperkowski Angela , Bauch Terry D. , Chan Joseph Y.S. , Arnold Ahran D. , Whinnett Zachary I. , Ellenbogen Kenneth A. , Vijayaraman Pugazhendhi
Published: September 2018

Background

Cardiac resynchronization therapy utilizing biventricular pacing is an effective therapy for patients with left ventricular (LV) systolic dysfunction, left bundle branch block, and heart failure. Benefits of biventricular pacing may be limited in patients with right bundle branch block (RBBB). Permanent His bundle pacing (HBP) has recently been reported as an option for cardiac resynchronization therapy. The aim of the study was to assess the feasibility and outcomes of HBP in patients with RBBB and heart failure.

Methods

HBP was attempted as a primary or rescue (failed LV lead implant) strategy in patients with reduced LV ejection fraction, RBBB, QRS duration ≥120 ms, and New York Heart Association class II to IV heart failure. Implant characteristics, New York Heart Association functional class, and echocardiographic data were assessed in follow-up.

Results

Mean age was 72±10 years, female 15%, with an average LV ejection fraction of 31±10%. HBP was successful in 37 of 39 patients (95%) with narrowing of RBBB in 78% cases. His capture and bundle branch block correction thresholds were 1.1±0.6 V and 1.4±0.7 V at 1 ms, respectively. During a mean follow-up of 15±23 months, there was a significant narrowing of QRS from 158±24 to 127±17 ms (
P
=0.0001), increase in LV ejection fraction from 31±10% to 39±13% (
P
=0.004), and improvement in New York Heart Association functional class from 2.8±0.6 to 2±0.7 (
P
=0.0001) with HBP. Increase in capture threshold occurred in 3 patients.

Conclusions

Permanent HBP was associated with significant narrowing of QRS duration and improvement in LV function in patients with RBBB and reduced LV ejection fraction. Permanent HBP is a promising option for cardiac resynchronization therapy in patients with RBBB and reduced LV ejection fraction.
Clinical and In Vitro Evidence That Left Ventricular Assist Device–Induced von Willebrand Factor Degradation Alters Angiogenesis
Authors: Bartoli Carlo R. , Zhang David M. , Hennessy-Strahs Samson , Kang Jooeun , Restle David J. , Bermudez Christian , Atluri Pavan , Acker Michael A.
Published: September 2018

Background

Gastrointestinal bleeding from angiodysplasia is a major problem in continuous-flow left ventricular assist device (LVAD) patients. LVAD shear stress causes pathologic degradation of VWF (von Willebrand factor). A mechanistic relationship between VWF degradation and angiodysplasia has not been explored. We tested 2 novel hypotheses: (1) clinical hypothesis: VWF fragments are elevated in LVAD patients that develop angiodysplasia and (2) in vitro hypothesis: VWF fragments generated during LVAD support alter angiogenesis, which may contribute to angiodysplasia.

Methods and Results

Clinical study: Paired blood samples were collected from continuous-flow LVAD patients (n=35). VWF was quantified with immunoblotting. In vitro experiments: (1) To investigate whether LVAD support alters angiogenesis, human endothelial cells were cultured with LVAD patient plasma (n=11). To investigate mechanism, endothelial cells were cultured with VWF fragments produced by exposing human VWF and ADAMTS-13 (VWF protease) to LVAD-like shear stress (175 dyne/cm
2
, n=8). Clinical study results: in all patients (n=35, mean support 666±430 days), LVAD support degraded high-molecular-weight VWF multimers (
P
<0.0001) into low-molecular-weight VWF multimers (
P
<0.0001) and VWF fragments (
P
<0.0001). In patients with gastrointestinal bleeding from angiodysplasia (n=7), VWF fragments were elevated (
P
=0.02) versus nonbleeders. In contrast, in patients with gastrointestinal bleeding without angiodysplasia, VWF fragments were not elevated versus nonbleeders (
P
=0.96). In vitro experiments results: LVAD patient plasma caused abnormal angiogenesis with reduced tubule length (
P
=0.04) and migration (
P
=0.05). Similarly, endothelial cells grown with VWF degradation fragments exhibited reduced tubule length (
P
<0.001) and migration (
P
=0.01).

Conclusions

LVAD patients who bled from angiodysplasia had higher levels of VWF fragments than nonbleeders and gastrointestinal bleeders without angiodysplasia. VWF fragments caused abnormal angiogenesis in vitro. These findings suggest that VWF fragments may be a mechanistic link between LVAD support, abnormal angiogenesis, angiodysplasia, and gastrointestinal bleeding.
Early Natural History of Spontaneous Coronary Artery Dissection
Authors: Waterbury Thomas M. , Tweet Marysia S. , Hayes Sharonne N. , Eleid Mackram F. , Bell Malcolm R. , Lerman Amir , Singh Mandeep , Best Patricia J.M. , Lewis Bradley R. , Rihal Charanjit S. , Gersh Bernard J. , Gulati Rajiv
Published: September 2018

Background:

Risks and mechanisms of extension of conservatively managed spontaneous coronary artery dissection (SCAD) remain incompletely understood. Study objectives were to (1) evaluate mechanisms of early SCAD evolution through serial angiographic analysis, and (2) determine predictors of early SCAD progression.

Methods and Results:

Retrospective registry study of patients with SCAD managed with an initial conservative strategy (n=240). Patients who experienced significant SCAD progression within 14 days, defined as clinical worsening plus new critical coronary obstruction on repeat angiography, were compared with remaining controls. A total of 42 of 240 (17.5%) experienced significant SCAD progression after index conservative approach; 91% by day 6. Isolated intramural hematoma (IMH) at baseline (no intimal dissection) was observed more frequently in those experiencing progression compared with controls (69.1% versus 44.4%;
P
=0.004). Multivariable predictors of SCAD progression included lesion severity, multivessel involvement, and isolated IMH. To investigate mechanisms of SCAD evolution, all repeat angiograms ≤14 days were compared with corresponding baselines (n=82 patient angiogram pairs). Of those with isolated IMH at baseline, 20% developed intimal dissection at repeat study. IMH was associated with greater longitudinal lesion extension (11.5 versus 2.8 mm;
P
=0.01), worsening Thrombolysis in Myocardial Infarction flow (−0.8 versus 0.1;
P
=0.003), and a nonsignificant lower rate of angiographic improvement (20.0% versus 31.3%;
P
=0.16) compared with the group with baseline intimal dissection. Optical coherence tomography subgroup analysis (n=17) indicated intimo-medial thickness to be lowest at the midpoint of IMH.

Conclusions:

Conservatively managed SCAD carries a 1:6 hazard for serious deterioration within 6 days. The risk was higher in those with isolated IMH at baseline. IMH often precedes development of intimal dissection, which has implications for mechanisms of SCAD.
Long-Term Outcomes After Transcatheter Aortic Valve-in-Valve Replacement
Authors: de Freitas Campos Guimarães Leonardo , Urena Marina , Wijeysundera Harindra C. , Munoz-Garcia Antonio , Serra Vicenç , Benitez Luis M. , Auffret Vincent , Cheema Asim N. , Amat-Santos Ignacio J. , Fisher Quentin , Himbert Dominique , Garcia del Blanco Bruno , Dager Antonio , Le Breton Hervé , Paradis Jean-Michel , Dumont Eric , Pibarot Philippe , Rodés-Cabau Josep
Published: September 2018

Background:

Data on long-term outcomes after valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) are scarce. The objective of this study was to determine the long-term clinical outcomes and structural valve degeneration (SVD) over time in patients undergoing ViV-TAVR.

Methods and Results:

Consecutive patients undergoing ViV-TAVR in 9 centers between 2009 and 2015 were included. Patients were followed yearly, and clinical and echocardiography data were collected prospectively. SVD was defined as subclinical (increase >10 mm Hg in mean transvalvular gradient+decrease >0.3 cm
2
in valve area or new-onset mild or moderate aortic regurgitation) and clinically relevant (increase >20 mm Hg in mean transvalvular gradient+decrease >0.6 cm
2
in valve area or new-onset moderate-to-severe aortic regurgitation). A total of 116 patients (mean age, 76±11 years; 64.7% male; mean Society of Thoracic Surgeons score, 8.0±5.1%) were included. Balloon- and self-expandable valves were used in 47.9% and 52.1% of patients, respectively, and 30-day mortality was 6.9%. At a median follow-up of 3 years (range, 2–7 years), 30 patients (25.9%) had died, 20 of them (17.2%) from cardiovascular causes. Average mean transvalvular gradients remained stable up to 5-year follow-up (
P
=0.92), but clinically relevant SVD occurred in 3/99 patients (3.0%), and 15/99 patients (15.1%) had subclinical SVD. One patient with SVD had redo ViV-TAVR.

Conclusions:

About one-fourth of ViV-TAVR recipients had died after a median follow-up of 3 years. Overall valve hemodynamics remained stable over time and clinically relevant SVD was infrequent, but 1 out of 10 patients exhibited some degree of SVD.
Fall Risk and Outcomes Among Patients Hospitalized With Cardiovascular Disease in the Community
Authors: Manemann Sheila M. , Chamberlain Alanna M. , Boyd Cynthia M. , Miller Donna M. , Poe Kimberly L. , Cheville Andrea , Weston Susan A. , Koepsell Ellen E. , Jiang Ruoxiang , Roger Véronique L.
Published: September 2018

Background

As the population with cardiovascular disease ages, geriatric conditions are of increasing relevance. A possible geriatric prognostic indicator may be a fall risk score, which is mandated by The Joint Commission to be measured on all hospitalized patients. The prognostic value of a fall risk score on outcomes after dismissal is not well known. Thus, we aimed to determine whether a fall risk score is associated with death and hospital readmissions in patients with a recent incident cardiovascular disease event.

Methods and Results

In this retrospective cohort study, Olmsted County, MN patients with incident heart failure, myocardial infarction, or atrial fibrillation between August 1, 2005, and December 31, 2011, who were hospitalized within 180 days after the event were studied. Fall risk was measured by the Hendrich II fall risk model. Patients were followed for death or readmission within 30 days or 1 year. Among 2456 hospitalized patients with recent incident cardiovascular disease (549 heart failure, 784 myocardial infarction, 1123 atrial fibrillation; mean [SD] age, 71 [15] years; 55% men), the fall risk score was high in 22% of patients and moderate in 38%. The risk of death was increased if the fall risk score was increased, independent of age and comorbidities (moderate hazard ratio, 1.51; 95% CI, 1.09–2.08; high hazard ratio, 3.49; 95% CI, 2.52–4.85). Similarly, the risk of 30-day readmissions was substantially increased with a greater fall risk score (moderate hazard ratio, 1.29; 95% CI, 1.03–1.62; high hazard ratio, 1.63; 95% CI, 1.23–2.15). Results were similar for readmissions within 1 year.

Conclusions

More than half of hospitalized patients with recent incident cardiovascular disease have an elevated fall risk score, which is associated with an increased risk in readmissions and death. These results delineate an approach for risk stratification and management that may prevent readmissions and improve survival.
Association Between Postoperative Pneumonia and 90-Day Episode Payments and Outcomes Among Medicare Beneficiaries Undergoing Cardiac Surgery
Authors: Thompson Michael P. , Cabrera Lourdes , Strobel Raymond J. , Harrington Steven D. , Zhang Min , Wu Xiaoting , Prager Richard L. , Likosky Donald S.
Published: September 2018

Background

Postoperative pneumonia is the most common healthcare-associated infection in cardiac surgical patients, yet their impact across a 90-day episode of care remains unknown. Our objective was to examine the relationship between pneumonia and 90-day episode payments and outcomes among Medicare beneficiaries undergoing cardiac surgery.

Methods and Results

Medicare claims were used to identify beneficiaries with episodes of coronary artery bypass grafting (CABG; n=56 728) and valve surgery (n=56 377) across 1045 centers between April 2014 and March 2015. Using a published diagnosis code-based algorithm, we identified pneumonia in 6.4% CABG episodes and 6.6% of valve surgery episodes. We compared price-standardized 90-day episode payments and outcome measures (postoperative length of stay, discharge to postacute care, mortality, and readmission) between beneficiaries with and without pneumonia using hierarchical regression models, adjusting for patient factors and hospital random effects. Pneumonia was associated with 24.5% higher episode payments for CABG ($46 723 versus $37 496;
P
<0.001) and 26.5% higher episode payments for valve surgery ($61 544 versus $48 549;
P
<0.001). For both cohorts, pneumonia was significantly associated with longer postoperative length of stay (CABG: +4.1 days, valve: +5.6 days), more frequent discharge to postacute care (CABG: odds ratio [OR]=1.99, valve: OR=2.17), and higher rates of 30-day mortality (CABG: OR=2.42, valve: OR=2.57) and 90-day readmission (CABG: OR=1.20, valve: OR=1.25), all
P
<0.001. We compared episode payments and outcomes across terciles of pneumonia rates and found that high pneumonia rate hospitals had higher episode payments and poorer outcomes compared with episodes at low pneumonia rate hospitals in both CABG and valve surgery cohorts.

Conclusions

Postoperative pneumonia was associated with significantly higher 90-day episode payments and inferior outcomes at the patient and hospital level. Future work should examine whether reducing pneumonia after cardiac surgery reduces episode spending and improves outcomes, which could facilitate hospital success in value-based reimbursement programs.
Insights From the International Registry of Acute Aortic Dissection
Authors: Evangelista Arturo , Isselbacher Eric M. , Bossone Eduardo , Gleason Thomas G. , Eusanio Marco Di , Sechtem Udo , Ehrlich Marek P. , Trimarchi Santi , Braverman Alan C. , Myrmel Truls , Harris Kevin M. , Hutchinson Stuart , O’Gara Patrick , Suzuki Toru , Nienaber Christoph A. , Eagle Kim A.
Published: September 2018

Acute aortic dissection (AAD) is a life-threatening condition associated with high morbidity and mortality rates, and it remains a challenge to diagnose and treat. The International Registry of Acute Aortic Dissection was established in 1996 with the mission to raise awareness of this condition and provide insights to guide diagnosis and treatment. Since then, >7300 cases have been included from >51 sites in 12 countries. Although presenting symptoms and physical findings have not changed significantly over this period, the use of computed tomography in the diagnosis has increased, and more patients are managed with interventional procedures: surgery in type A AAD and endovascular therapy in type B AAD; with these changes in care, there has been a significant decrease in overall in-hospital mortality in type A AAD but not in type B AAD. Herein, we summarized the key lessons learned from this international registry of patients with AAD over the past 20 years.
Management of Intraprocedural Anticoagulation in Patients on Non-Vitamin K Antagonist Oral Anticoagulants Undergoing Catheter Ablation for Atrial Fibrillation
Authors: Martin Anne-Céline , Godier Anne , Narayanan Kumar , Smadja David M. , Marijon Eloi
Published: September 2018

Catheter ablation has gained a prominent role in the management of atrial fibrillation (AF), with recent data providing positive evidence on hard outcomes, including hospitalization and mortality. Ablation, however, exposes the patient to a rather unique situation, combining risks for both major bleeding and thromboembolic events. In this setting, the critical importance of rigorous anticoagulation during the procedure has been underlined, and the latest international guidelines now recommend performing AF catheter ablation with uninterrupted non-vitamin K antagonist oral anticoagulants (NOACs) and concomitant administration of unfractionated heparin adjusted to achieve and maintain a target activated clotting time of ≥300 seconds. Whereas observational studies and randomized controlled trials support the safety and efficacy of uninterrupted NOAC strategy for AF catheter ablation, recent experiences have questioned this point, showing a greater unfractionated heparin requirement in NOAC-treated patients compared with vitamin K antagonists–treated patients to achieve the target activated clotting time. Important gaps in evidence regarding optimal intraprocedural anticoagulation management need to be acknowledged. A thorough appreciation of the physiology of anticoagulation during AF catheter ablation and the relevant differences between vitamin K antagonists and NOACs is required, while also understanding the limitations of activated clotting time measurement with regard to accurate intraprocedural anticogulation monitoring. This review aims to provide a critical look at this relatively ignored aspect of AF catheter ablation, especially pitfalls in NOAC monitoring, and to identify gaps in knowledge that need to be addressed in the near future.
Synergistic Opportunities in the Interplay Between Cancer Screening and Cardiovascular Disease Risk Assessment
Authors: Handy Catherine E. , Quispe Renato , Pinto Xavier , Blaha Michael J. , Blumenthal Roger S. , Michos Erin D. , Lima Joao A.C. , Guallar Eliseo , Ryu Seungho , Cho Juhee , Kaye James A. , Comin-Colet Josep , Corbella Xavier , Cainzos-Achirica Miguel
Published: September 2018

Cardiovascular disease (CVD) and cancer continue to be the 2 leading causes of death in developed countries despite significant improvements in the prevention, screening, and treatment of both diseases. They remain significant public health problems, growing in importance globally. Despite this threat, the fields of cardiology and oncology have been relatively disconnected. With many shared modifiable risk factors, cancer and CVD often coexist in the same individuals; those diagnosed with lung cancer, breast cancer, and colon cancer are at higher risk of CVD, and those with CVD are at higher risk of developing many types of common cancers. Screening paradigms have been established in parallel, but there are opportunities for combined risk assessments for cancer and CVD risk. Joining forces for combined cardiovascular and hemato-oncological preventive and research efforts will likely have synergistic, worldwide public health benefits.
Hemodynamic Response to Gabapentin in Conscious Spontaneously Hypertensive Rats
Authors: Behuliak Michal , Bencze Michal , Polgárová Kamila , Kuneš Jaroslav , Vaněčková Ivana , Zicha Josef
Published: September 2018

Ligands of auxiliary α
2
δ subunit of voltage-dependent calcium channels (VDCCs) decrease elevated L-type VDCCs surface expression in arterial myocytes and arterial constriction in spontaneously hypertensive rats (SHR). However, their effect on blood pressure (BP) is unclear. In this study, we investigated the hemodynamic response to acute and chronic administration of gabapentin, a ligand of auxiliary α
2
δ subunit of VDCCs, in adult SHR with established neurogenic hypertension. The acute gabapentin administration lowered BP and heart rate more in conscious SHR than Wistar-Kyoto rats. Both nifedipine (L-type VDCCs blocker) and ω-conotoxin GVIA (N-type VDCCs blocker) also decreased BP more in SHR, but only gabapentin and ω-conotoxin GVIA abolished the nitroprusside-induced reflex tachycardia of baroreceptor-heart rate control. Hypotensive effect of gabapentin was accompanied by a reduction of (1) plasma norepinephrine level, (2) depressor response to ganglionic blocker pentolinium, (3) power of low frequency component of systolic BP variability, and (4) pressor response of mesenteric vascular bed to periarterial nerve stimulation, suggesting the decrease of peripheral sympathetic nerve transmission. Moreover, gabapentin effects on BP and baroreflex were absent in sympathectomized rats. In conclusion, the acute (but not chronic) administration of gabapentin lowered BP more in SHR than in Wistar-Kyoto rats. Besides the known L-type VDCCs involvement in the vascular effect of gabapentin, our data revealed the important role of N-type VDCCs in acute gabapentin effect on sympathetic control of BP. Gabapentin-induced changes of sympathetic nerve transmission indicated major hemodynamic mechanism of the acute response to this drug.
Classical Cardiovascular Risk Markers in Pregnancy and Associations to Uteroplacental Acute Atherosis
Authors: Moe Kjartan , Alnaes-Katjavivi Patji , Størvold Gro L. , Sugulle Meryam , Johnsen Guro M. , Redman Christopher W.G. , Dechend Ralf , Staff Anne C.
Published: September 2018

Uteroplacental acute atherosis (AA) is a pregnancy-specific arterial lesion resembling early stages of atherosclerosis. AA is frequent in preeclamptic pregnancies, which associate with increased long-term maternal risk of atherosclerotic cardiovascular disease. We hypothesized that AA in pregnant women associates with classical risk factors for cardiovascular disease, including hypertension, hyperlipidemia, glucose intolerance, elevated C-reactive protein, age, and body mass index. We included 237 women delivered by cesarean section (healthy pregnancies, n=94; preeclampsia, n=87; pregestational and gestational diabetes mellitus, n=39; diabetes mellitus with preeclampsia, n=17). They provided blood before delivery for biomarker analyses. AA was diagnosed by immunohistochemistry in uteroplacental (decidual) tissue collected after placental removal. Statistical analyses were performed with Mann-Whitney test. Levels of traditional cardiovascular markers were not associated with decidual AA within the groups of women with normotensive pregnancies, preeclampsia, diabetes mellitus, or diabetes mellitus superimposed with preeclampsia. However, the oldest patient age quartile (36–43 years old) with AA had significantly higher levels of LDL (low-density lipoprotein) and apolipoprotein B (both
P
<0.01) than women of the same age without AA. AA was associated with elevated median prepregnancy/early pregnancy systolic blood pressure (
P
=0.01) in the total cohort, but as preeclampsia was strongly associated with this finding (
P
<0.01), this was likely caused by a large proportion of preeclamptic pregnancies in the AA group (62.7%). Our findings demonstrate that dyslipidemia associated with cardiovascular risk is a feature of uteroplacental AA in older women, not of AA in pregnancy in general.
Initial Antihypertensive Treatment Strategies and Therapeutic Inertia
Authors: Rea Federico , Corrao Giovanni , Merlino Luca , Mancia Giuseppe
Published: September 2018

In many hypertensive patients, treatment is not upgraded despite lack of blood pressure control because of therapeutic inertia. Information is limited, however, on the extent of this phenomenon in real-life medicine. We studied 125 635 patients (age 40–85 years) from the Lombardy region (Italy) who started antihypertensive treatment with 1 drug (n=100 982) or a 2-drug fixed-dose or free combination (n=24 653). A log-binomial regression model was used to estimate the prevalence ratio of combination therapy in relation to the initial treatment strategy. In the initial monotherapy group, patients under drug combinations were 22%, 27%, 32%, and 36% at 6 months, 1, 2, and 3 years later. In the initial combination treatment group, the corresponding percentages were 85%, 82%, 79%, and 78%. This translated into a markedly greater covariate-adjusted propensity of being under a multidrug prescription throughout the follow-up: 3.92 (95% CI, 3.84–4.00) after 6 months and 3.18 (3.12–3.25), 2.56 (2.51–2.60), and 2.23 (2.19–2.27) after 1, 2 and 3 years of treatment. In a propensity score analysis, initial 2-drug combination treatment was also associated with significant reductions in the risk of death (−20%, 11% to 28%) and hospitalization for cardiovascular events (−16%, 10% to 21%) compared with initial monotherapy. Thus, in real life, a large number of patients prescribed initial monotherapy fails to move to combination treatment, as recommended by guidelines. This implies that therapeutic inertia frequently prevents proper treatment uptitration, thereby playing a major role in the low rate of hypertension control that exists worldwide.
Exosome-Mediated Transfer of ACE (Angiotensin-Converting Enzyme) From Adventitial Fibroblasts of Spontaneously Hypertensive Rats Promotes Vascular Smooth Muscle Cell Migration
Authors: Tong Ying , Ye Chao , Ren Xing-Sheng , Qiu Yun , Zang Ying-Hao , Xiong Xiao-Qing , Wang Jue-Jin , Chen Qi , Li Yue-Hua , Kang Yu-Ming , Zhu Guo-Qing
Published: September 2018

Migration of vascular smooth muscle cells (VSMCs) is pivotal for vascular remodeling in hypertension. Vascular adventitial fibroblasts (AFs) are important in the homeostasis of vascular structure. This study is designed to investigate the roles of AF exosomes (AFE) in VSMC migration and underling mechanism. Primary VSMCs and AFs were obtained from the aorta of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. VSMC migration was evaluated with Boyden chamber assay and wound healing assay. AFE from WKY rats and SHR were isolated and identified. AFE from SHR promoted but AFE from WKY rats had no significant effect on VSMC migration. The effects of AFE on VSMC migration were prevented by an exosome inhibitor GW4869, an AT
1
R (Ang II [angiotensin II] type 1 receptor) antagonist losartan, or an inhibitor of ACE (angiotensin-converting enzyme) captopril. ACE contents and activity were much higher in AFE from SHR than those from WKY rats. There were no significant difference in Ang II and AT
1
R mRNA and protein levels between AFE from SHR and AFE from WKY rats. AFE from SHR increased Ang II and ACE contents and ACE activity in VSMCs of WKY rats and SHR. The changes of Ang II contents and ACE activity were prevented by captopril. ACE knockdown in AFs reduced ACE contents and activity in AFE from SHR and inhibited AFE-induced migration of VSMCs of WKY rats and those of SHR. These results indicate that exosomes from AFs of SHR transfer ACE to VSMCs, which increases Ang II levels and activates AT
1
R in VSMCs and thereby promotes VSMC migration.
Novel Pathogenesis of Hypertension and Diastolic Dysfunction Caused by M3R (Muscarinic Cholinergic 3 Receptor) Signaling
Authors: Deng Alan Y. , deBlois Denis , Laporte Stéphane A. , Gelinas Danielle , Tardif Jean-Claude , Thorin Eric , Shi Yanfen , Raignault Adeline , Ménard Annie
Published: September 2018

Multiple quantitative trait loci for blood pressure (BP) are localized in humans and rodent models. Model studies have not only produced human quantitative trait loci homologues but also provided unforeseen mechanistic insights into the function modality of quantitative trait loci actions. Presently, congenic knockins, gene-specific knockout, and in vitro and in vivo function studies were used in a rat model of polygenic hypertension, DSS (Dahl salt sensitive) rats. One gene previously unknown in regulating BP was detected with 1 structural mutation(s) for each of 2 quantitative trait loci classified into 2 separate epistatic modules 1 and 3.
C17QTL1
in epistatic module 2 was identified to be the gene
Chrm3
encoding the M3R (muscarinic cholinergic 3 receptor), since a single function-enhancing M3R
T556M
conversion correlated with elevated BP. To definitively prove that the enhanced M3R function is responsible for BP changes by the DSS alleles of
C17QTL1
, we generated a
Chrm3
gene-specific rat knockout. We observed a reduction in BP without tachycardia in both sexes, regardless of the amount of dietary salt, and an improvement in diastolic and kidney dysfunctions. All occurred in spite of a significant reduction in M3R-dependent vasodilation. The previously seen sexual dimorphism for
C17QTL1
on BP disappeared in the absence of M3R. A
Chrm3
-coding variation increased M3R signaling, correlating with higher BP. Removing the M3R signaling led to a decrease in BP and improvements in cardiac and renal malfunctions. A novel pathogenic pathway accounted for a portion of polygenic hypertension and has implications in applying new diagnostic and therapeutic uses against hypertension and diastolic dysfunction.