bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spotlight on advances in VTE management: CALLISTO and EINSTEIN CHOICE
Authors: Bach Miriam , Bauersachs Rupert 
Published: September 2016

SummaryVenous thromboembolism (VTE) is associated with numerous complications and high mortality rates. Patients with cancer are at high risk of developing cancer-associated thrombosis (CAT), and VTE recurrence is common. Evidence supporting use of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in patients with cancer is lacking – direct comparisons between NOACs and low-molecular-weight heparin (LMWH) are needed, along with patient-reported outcomes. Cancer Associated thrombosis – expLoring soLutions for patients through Treatment and Prevention with RivarOxaban (CALLISTO) is an international research programme exploring the potential of the direct, oral factor Xa inhibitor rivaroxaban for the prevention and treatment of CAT, supplementing existing data from EINSTEIN DVT and EINSTEIN PE. Here, we focus on four CALLISTO studies: A Study to Evaluate the Efficacy and Safety of Rivaroxaban Venous Thromboembolism Prophylaxis in Ambulatory Cancer Participants receiving Chemotherapy (CASSINI), Antico-agulation Therapy in SELECTeD Cancer Patients at Risk of Recurrence of Venous Thromboembolism (SELECT-D), Rivaroxaban in the Treatment of Venous Thromboembolism in Cancer Patients – a Randomized Phase III Study (CONKO-011) and a database analysis. Optimal anticoagulation duration for VTE treatment has always been unclear. Following favourable results for rivaroxaban 20 mg once-daily (Q. D.) for secondary VTE prevention (EINSTEIN EXT), EINSTEIN CHOICE is assessing rivaroxaban safety and (20 mg Q. D. or 10 mg Q. D.) vs acetylsalicylic acid (ASA), and will investigate whether an alternative rivaroxaban dose (10 mg Q. D.) could offer long-term VTE protection. It is anticipated that results from these studies will provide important answers and expand upon current evidence for rivaroxaban in VTE management.
Recovery of Serum Cholesterol Predicts Survival After Left Ventricular Assist Device Implantation
Authors: Vest Amanda R. , Kennel Peter J. , Maldonado Dawn , Young James B. , Mountis Maria M. , Naka Yoshifumi , Colombo Paolo C. , Mancini Donna M. , Starling Randall C. , Schulze P. Christian 
Published: September 2016

Background—
Advanced systolic heart failure is associated with myocardial and systemic metabolic abnormalities, including low levels of total cholesterol and low-density lipoprotein. Low cholesterol and low-density lipoprotein have been associated with greater mortality in heart failure. Implantation of a left ventricular assist device (LVAD) reverses some of the metabolic derangements of advanced heart failure.

Methods and Results—
A cohort was retrospectively assembled from 2 high-volume implantation centers, totaling 295 continuous-flow LVAD recipients with ≥2 cholesterol values available. The cohort was predominantly bridge-to-transplantation (67%), with median age of 59 years and 49% ischemic heart failure cause. Total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels all significantly increased after LVAD implantation (median values from implantation to 3 months post implantation 125–150 mg/dL, 67–85 mg/dL, 32–42 mg/dL, and 97–126 mg/dL, respectively). On Cox proportional hazards modeling, patients achieving recovery of total cholesterol levels, defined as a median or greater change from pre implantation to 3 months post-LVAD implantation, had significantly better unadjusted survival (hazard ratio, 0.445; 95% confidence interval, 0.212–0.932) and adjusted survival (hazard ratio, 0.241; 95% confidence interval, 0.092–0.628) than those without cholesterol recovery after LVAD implantation. The continuous variable of total cholesterol at 3 months post implantation and the cholesterol increase from pre implantation to 3 months were also both significantly associated with survival during LVAD support.

Conclusions—
Initiation of continuous-flow LVAD support was associated with significant recovery of all 4 lipid variables. Patients with a greater increase in total cholesterol by 3 months post implantation had superior survival during LVAD support.
Predictors of Rehospitalization Among Adults With Congenital Heart Disease Are Lesion Specific
Authors: Cedars Ari M. , Burns Sara , Novak Eric L. , Amin Amit P. 
Published: September 2016

Background—
Readmission is responsible for a large proportion of inpatient care costs in adult congenital heart disease. There are, however, few data available to identify at-risk patients or to suggest strategies for intervention to prevent rehospitalization.

Methods and Results—

We conducted an analysis of admissions in patients over the age of 18 years with a 3-digit
International Classification of Diseases
-Ninth Revision code of 745 to 747 from the State Inpatient Databases of Arkansas (2008–2010), California (2003–2012), Florida (2005–2012), Hawaii (2006–2010), Nebraska (2003–2011), and New York (2005–2012). We investigated index admission diagnoses most commonly associated with 1-year readmission and the most common reasons for readmission. We then selected variables we thought would be associated with increased rates of 1-year readmission and constructed multivariable regression models grouping patients by congenital lesion, to examine the relative contribution of the specified variables to readmission risk for each lesion. A total of 64 420 patients were included in the final analysis. Thirty-nine percent of patients experienced a readmission within 12 months of an index admission. Compared with those who did not experience a readmission, those who did were more likely to have had a primary diagnosis of congestive heart failure at the time of index admission, and the most common diagnoses at the time of readmission were congestive heart failure and arrhythmia. There is lesion-specific heterogeneity in risk factors for readmission.

Conclusions—
Patients with adult congenital heart disease have high rates of readmission, predominantly for congestive heart failure and arrhythmia. Predictors of readmission are lesion specific, and future strategies aimed at decreasing readmission rate will likely need to be individualized.
Health Insurance Trajectories and Long-Term Survival After Heart Transplantation
Authors: Tumin Dmitry , Foraker Randi E. , Smith Sakima , Tobias Joseph D. , Hayes Don 
Published: September 2016

Background—
Health insurance status at heart transplantation influences recipient survival, but implications of change in insurance for long-term outcomes are unclear.

Methods and Results—

Adults aged 18 to 64 receiving first-time orthotopic heart transplants between July 2006 and December 2013 were identified in the United Network for Organ Sharing registry. Patients surviving >1 year were categorized according to trajectory of insurance status (private compared with public) at wait listing, transplantation, and 1-year follow-up. The most common insurance trajectories were continuous private coverage (44%), continuous public coverage (27%), and transition from private to public coverage (11%). Among patients who survived to 1 year (n=9088), continuous public insurance (hazard ratio =1.36; 95% confidence interval 1.19, 1.56;
P
<0.001) and transition from private to public insurance (hazard ratio =1.25; 95% confidence interval 1.04, 1.50;
P
=0.017) were associated with increased mortality hazard relative to continuous private insurance. Supplementary analyses of 11 247 patients included all durations of post-transplant survival and examined post-transplant private-to-public and public-to-private transitions as time-varying covariates. In these analyses, transition from private to public insurance was associated with increased mortality hazard (hazard ratio =1.25; 95% confidence interval 1.07, 1.47;
P
=0.005), whereas transition from public to private insurance was associated with lower mortality hazard (hazard ratio =0.78; 95% confidence interval 0.62, 0.97;
P
=0.024).

Conclusions—
Transition from private to public insurance after heart transplantation is associated with worse long-term outcomes, compounding disparities in post-transplant survival attributed to insurance status at transplantation. By contrast, post-transplant gain of private insurance among patients receiving publicly funded heart transplants was associated with improved outcomes.
Associations Between Macrophage Colony‐Stimulating Factor and Monocyte Chemotactic Protein 1 in Plasma and First‐Time Coronary Events: A Nested Case–Control Study
Authors: Schiopu Alexandru , Bengtsson Eva , Gonçalves Isabel , Nilsson Jan , Fredrikson Gunilla Nordin , Björkbacka Harry 
Published: September 2016

Background
Myeloid cells play a central role in atherosclerosis. We investigated the associations between the plasma levels of growth factors and chemokines that regulate myeloid cell homeostasis and function and the risk of first‐time acute coronary events in middle‐aged persons.

Methods and Results

We measured baseline plasma levels of macrophage colony‐stimulating factor; monocyte chemotactic protein 1; C‐C motif chemokine ligands 3, 4, and 20; C‐X‐C motif chemokine ligands 1, 6, and 16; and C‐X3‐C motif chemokine ligand 1 in 292 participants who had a coronary event during follow‐up and 366 controls matched for age, sex, and time of inclusion who remained event free. Study participants were recruited from the Malmö Diet and Cancer Study population cohort and had no previous history of coronary artery disease. We found a strong independent negative association between macrophage colony‐stimulating factor and incident coronary events in a forward stepwise Cox proportional hazards model including all biomarkers alongside the classic Framingham risk factors (age, sex, smoking, total cholesterol, high‐density lipoprotein cholesterol, systolic blood pressure), diabetes mellitus, and medication. Conversely, monocyte chemotactic protein 1 had the strongest independent positive association with the outcome. The addition of macrophage colony‐stimulating factor and monocyte chemotactic protein 1 significantly improved the predictive ability of a model including traditional risk factors alone (C statistic 0.81 [95%
CI
0.78–0.84] versus 0.67 [95%
CI
0.63–0.71]; net reclassification index 0.52 [0.42–0.62];
P
<0.001). The combined model led to a 54% net downclassification of participants who did not have a coronary event during follow‐up and was particularly effective in the intermediate‐risk group.

Conclusions
High levels of macrophage colony‐stimulating factor and low levels of monocyte chemotactic protein 1 in plasma characterize middle‐aged persons at low risk to develop clinically manifested coronary artery disease.
Urine Albumin/Creatinine Ratio Below 30 mg/g is a Predictor of Incident Hypertension and Cardiovascular Mortality
Authors: Sung Ki‐Chul , Ryu Seungho , Lee Jong‐Young , Lee Sung Ho , Cheong EunSun , Hyun Young‐Youl , Lee Kyu‐Beck , Kim Hyang , Byrne Christopher D. 
Published: September 2016

Background

Microalbuminuria is associated with cardiovascular disease (
CVD
) mortality, but whether lower levels of urine albumin excretion similarly predict
CVD
is uncertain. We investigated associations between urine albumin:creatinine ratio (
UACR
) <30 mg/g, and incident hypertension, incident diabetes mellitus, and all‐cause and
CVD
mortality, during a maximum of 11 years of follow‐up.

Methods and Results

Individuals (37 091) in a health screening program between 2002 and 2012 with baseline measurements of
UACR
were studied. Cox proportional hazards models were used to estimate hazard ratios (
HR
s) and 95% CIs for incident hypertension, incident diabetes mellitus, and mortality outcomes (lowest
UACR
quartile as reference) at follow‐up. For linear risk trends, the quartile rank was used as a continuous variable in regression models. Nine‐hundred sixty‐three cases of incident hypertension, 511 cases of incident diabetes mellitus, and 349 deaths occurred during follow‐up. In the fully adjusted models, there was a significant
HR
for the association between
UACR
and incident hypertension (highest
UACR
quartile
HR
1.95 [95%
CI
1.51, 2.53],
P
‐value for trend across
UACR
quartiles
P
<0.001). In contrast, the association between
UACR
and incident diabetes mellitus was not significant (highest
UACR
quartile,
HR
1.15 [95%
CI
0.79, 1.66],
P
‐value for trend
P
=0.20). For
CVD
mortality, with increasing
UACR
quartiles, there was a significant increase in
HR
across quartiles,
P
=0.029, (for all‐cause mortality,
P
=0.078).

Conclusions

Low levels of albuminuria,
UACR
below 30 mg/g, are associated with increased risk of incident hypertension and
CVD
mortality at follow‐up, but are not associated with increased risk of incident diabetes mellitus.
Variants in the
SCN5A
Promoter Associated With Various Arrhythmia Phenotypes
Authors: Yagihara Nobue , Watanabe Hiroshi , Barnett Phil , Duboscq‐Bidot Laetitia , Thomas Atack C. , Yang Ping , Ohno Seiko , Hasegawa Kanae , Kuwano Ryozo , Chatel Stéphanie , Redon Richard , Schott Jean‐Jacques , Probst Vincent , Koopmann Tamara T. , Bezzina Connie R. , Wilde Arthur A. M. , Nakano Yukiko , Aiba Takeshi , Miyamoto Yoshihiro , Kamakura Shiro , Darbar Dawood , Donahue Brian S. , Shigemizu Daichi , Tanaka Toshihiro , Tsunoda Tatsuhiko , Suda Masayoshi , Sato Akinori , Minamino Tohru , Endo Naoto , Shimizu Wataru , Horie Minoru , Roden Dan M. , Makita Naomasa 
Published: September 2016

Background

Mutations in the coding sequence of

SCN
5A

, which encodes the cardiac Na
+
channel α subunit, have been associated with inherited susceptibility to various arrhythmias. Variable expression of

SCN
5A

is a possible mechanism responsible for this pleiotropic effect; however, it is unknown whether variants in the promoter and regulatory regions of

SCN
5A

also modulate the risk of arrhythmias.

Methods and Results

We resequenced the core promoter region of

SCN
5A

and the regulatory regions of

SCN
5A

transcription in 1298 patients with arrhythmia phenotypes (atrial fibrillation, n=444; sinus node dysfunction, n=49; conduction disease, n=133; Brugada syndrome, n=583; and idiopathic ventricular fibrillation, n=89). We identified 26 novel rare variants in the

SCN
5A

promoter in 29 patients affected by various arrhythmias (atrial fibrillation, n=6; sinus node dysfunction, n=1; conduction disease, n=3; Brugada syndrome, n=14; idiopathic ventricular fibrillation, n=5). The frequency of rare variants was higher in patients with arrhythmias than in controls. In the alignment with chromatin immunoprecipitation sequencing data, the majority of variants were located at regions bound by transcription factors. Using a luciferase reporter assay, 6 variants (Brugada syndrome, n=3; idiopathic ventricular fibrillation, n=2; conduction disease, n=1) were functionally characterized, and each displayed decreased promoter activity compared with the wild‐type sequences. We also identified rare variants in the regulatory region that were associated with atrial fibrillation, and the variant decreased promoter activity.

Conclusions

Variants in the core promoter region and the transcription regulatory region of

SCN
5A

were identified in multiple arrhythmia phenotypes, consistent with the idea that altered

SCN
5A

transcription levels modulate susceptibility to arrhythmias.
ASPECTS (Alberta Stroke Program Early CT Score) Assessment of the Perfusion–Diffusion Mismatch
Authors: Lassalle Louis , Turc Guillaume , Tisserand Marie , Charron Sylvain , Roca Pauline , Lion Stephanie , Legrand Laurence , Edjlali Myriam , Naggara Olivier , Meder Jean-François , Mas Jean-Louis , Baron Jean-Claude , Oppenheim Catherine 
Published: September 2016

Background and Purpose—
Rapid and reliable assessment of the perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mismatch is required to promote its wider application in both acute stroke clinical routine and trials. We tested whether an evaluation based on the Alberta Stroke Program Early CT Score (ASPECTS) reliably identifies the PWI/DWI mismatch.

Methods—

A total of 232 consecutive patients with acute middle cerebral artery stroke who underwent pretreatment magnetic resonance imaging (PWI and DWI) were retrospectively evaluated. PWI-ASPECTS and DWI-ASPECTS were determined blind from manually segmented PWI and DWI volumes. Mismatch-ASPECTS was defined as the difference between PWI-ASPECTS and DWI-ASPECTS (a high score indicates a large mismatch). We determined the mismatch-ASPECTS cutoff that best identified the volumetric mismatch, defined as Volume

T
max>6s

/Volume
DWI
≥1.8, a volume difference≥15 mL, and a Volume
DWI
<70 mL.

Results—

Inter-reader agreement was almost perfect for PWI-ASPECTS (κ=0.95 [95% confidence interval, 0.90–1]), and DWI-ASPECTS (κ=0.96 [95% confidence interval, 0.91–1]). There were strong negative correlations between volumetric and ASPECTS-based assessments of DWI lesions (ρ=−0.84,
P
<0.01) and PWI lesions (ρ=-0.90,
P
<0.01). Receiver operating characteristic curve analysis showed that a mismatch-ASPECTS ≥2 best identified a volumetric mismatch, with a sensitivity of 0.93 (95% confidence interval, 0.89–0.98) and a specificity of 0.82 (95% confidence interval, 0.74–0.89).

Conclusions—
The mismatch-ASPECTS method can detect a true mismatch in patients with acute middle cerebral artery stroke. It could be used for rapid screening of patients with eligible mismatch, in centers not equipped with ultrafast postprocessing software.
Brief Screening of Vascular Cognitive Impairment in Patients With Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Without Dementia
Authors: Brookes Rebecca L. , Hollocks Matthew J. , Tan Rhea Y.Y. , Morris Robin G. , Markus Hugh S. 
Published: September 2016

Background and Purpose—
Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic form of cerebral small vessel disease leading to early-onset stroke and dementia, with younger patients frequently showing subclinical deficits in cognition. At present, there are no targeted cognitive screening measures for this population. However, the Brief Memory and Executive Test (BMET) and the Montreal Cognitive Assessment (MoCA) have shown utility in detecting cognitive impairment in sporadic small vessel disease. This study assesses the BMET and the MoCA as clinical tools for detecting mild cognitive deficits in CADASIL.

Methods—
Sixty-six prospectively recruited patients with CADASIL, and 66 matched controls completed the BMET, with a subset of these also completing the MoCA. Receiver operating characteristic curves were calculated to examine the sensitivity and specificity of clinical cutoffs for the detection of vascular cognitive impairment and reduced activities of daily living.

Results—
Patients with CADASIL showed more cognitive impairment overall and were poorer on both executive/processing and memory indices of the BMET relative to controls. The BMET showed good accuracy in predicting vascular cognitive impairment (85% sensitivity and 84% specificity) and impaired instrumental activities of daily living (92% sensitivity and 77% specificity). The MoCA also showed good predictive validity for vascular cognitive impairment (80% sensitivity and 78% specificity) and instrumental activities of daily living (75% sensitivity and 76% specificity). The most important background predictor of vascular cognitive impairment was a history of stroke.

Conclusions—
The results indicate that the BMET and the MoCA are clinically useful and sensitive screening measures for early cognitive impairment in patients with CADASIL.
Association Between Carotid Bulb Diaphragm and Ischemic Stroke in Young Afro-Caribbean Patients
Authors: Joux Julien , Boulanger Marion , Jeannin Severine , Chausson Nicolas , Hennequin Jean-Luc , Molinié Vincent , Smadja Didier , Touzé Emmanuel , Olindo Stephane 
Published: September 2016

Background and Purpose—
Carotid bulb diaphragm (CBD) has been described in young carotid ischemic stroke (CIS) patients, especially in blacks. However, the prevalence of CBD in CIS patients is unknown, and whether CBD is a risk factor for CIS remains unclear. We assessed the association between CBD and incident CIS in a population-based study.

Methods—
We selected all young (<55 years) CIS patients from a 1-year population-based cohort study in the Afro-Caribbean population of Martinique in 2012. All patients had a comprehensive work-up including a computed tomographic angiography. We calculated CIS associated with ipsilateral CBD incidence with 95% confidence intervals using Poisson distribution. We then selected age- and sex-matched controls among young (<55 years) Afro-Caribbean stroke-free patients admitted for a road crash who routinely had computed tomographic angiography. Odds ratio (ORs) were calculated by conditional logistic regression adjusted for hypertension, dyslipidemia, diabetes and smoking.

Results—
CIS associated with ipsilateral CBD incidence was 3.8 per 100 000 person-years (95% confidence interval, 1.4–6.1). Prevalence of ipsilateral CBD was 23% in all CIS and 37% in undetermined CIS patients. When restricted to undetermined CIS, CBD prevalence was 24 times higher than that in controls (adjusted OR, 24.1; 95% confidence interval, 1.8–325.6).

Conclusions—
CBD is associated with an increased risk of ipsilateral CIS in young Afro-Caribbean population.
Rebalancing Spatial Attention: Endogenous Orienting May Partially Overcome the Left Visual Field Bias in Rapid Serial Visual Presentation
Authors: Śmigasiewicz Kamila , Hasan Gabriel Sami , Verleger Rolf 
Published: September 2016

Abstract
In dynamically changing environments, spatial attention is not equally distributed across the visual field. For instance, when two streams of stimuli are presented left and right, the second target (T2) is better identified in the left visual field (LVF) than in the right visual field (RVF). Recently, it has been shown that this bias is related to weaker stimulus-driven orienting of attention toward the RVF: The RVF disadvantage was reduced with salient task-irrelevant valid cues and increased with invalid cues. Here we studied if also endogenous orienting of attention may compensate for this unequal distribution of stimulus-driven attention. Explicit information was provided about the location of T1 and T2. Effectiveness of the cue manipulation was confirmed by EEG measures: decreasing alpha power before stream onset with informative cues, earlier latencies of potentials evoked by T1-preceding distractors at the right than at the left hemisphere when T1 was cued left, and decreasing T1- and T2-evoked N2pc amplitudes with informative cues. Importantly, informative cues reduced (though did not completely abolish) the LVF advantage, indicated by improved identification of right T2, and reflected by earlier N2pc latency evoked by right T2 and larger decrease in alpha power after cues indicating right T2. Overall, these results suggest that endogenously driven attention facilitates stimulus-driven orienting of attention toward the RVF, thereby partially overcoming the basic LVF bias in spatial attention.