bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Poor Prognosis Subtype of HNSCC Is Consistently Observed across Methylome, Transcriptome, and miRNome Analysis
Authors: Jung Alain C. , Job Sylvie , Ledrappier Sonia , Macabre Christine , Abecassis Joseph , de Reyniès Aurélien , Wasylyk Bohdan 
Published: June 2013

Abstract
Purpose: Distant metastasis after treatment is observed in about 20% of squamous cell carcinoma of the head and neck (HNSCC). In the absence of any validated robust biomarker, patients at higher risk for metastasis cannot be provided with tailored therapy. To identify prognostic HNSCC molecular subgroups and potential biomarkers, we have conducted genome-wide integrated analysis of four omic sets of data.
Experimental Design: Using state-of-the-art technologies, a core set of 45 metastasizing and 55 nonmetastasizing human papillomavirus (HPV)-unrelated HNSCC patient samples were analyzed at four different levels: gene expression (transcriptome), DNA methylation (methylome), DNA copy number (genome), and microRNA (miRNA) expression (miRNome). Molecular subgroups were identified by a model-based clustering analysis. Their clinical relevance was evaluated by survival analysis, and functional significance by pathway enrichment analysis.
Results: Patient subgroups selected by transcriptome, methylome, or miRNome integrated analysis are associated with shorter metastasis-free survival (MFS). A common subgroup, R1, selected by all three omic approaches, is statistically more significantly associated with MFS than any of the single omic-selected subgroups. R1 and non-R1 samples display similar DNA copy number landscapes, but more frequent chromosomal aberrations are observed in the R1 cluster (especially loss at 13q14.2-3). R1 tumors are characterized by alterations of pathways involved in cell–cell adhesion, extracellular matrix (ECM), epithelial-to-mesenchymal transition (EMT), immune response, and apoptosis.
Conclusions: Integration of data across several omic profiles leads to better selection of patients at higher risk, identification of relevant molecular pathways of metastasis, and potential to discover biomarkers and drug targets. Clin Cancer Res; 19(15); 4174–84. ©2013 AACR.
Transcatheter Aortic Valve Implantation for Patients With Severe Bicuspid Aortic Valve Stenosis
Authors: Hayashida Kentaro , Bouvier Erik , Lefèvre Thierry , Chevalier Bernard , Hovasse Thomas , Romano Mauro , Garot Philippe , Watanabe Yusuke , Farge Arnaud , Donzeau-Gouge Patrick , Cormier Bertrand , Morice Marie-Claude 
Published: June 2013

Background—
Bicuspid aortic valve (BAV) is regarded as a relative contraindication to transcatheter aortic valve implantation attributable to the risk of uneven expansion of the bioprosthesis. The purpose of this study was to evaluate the efficacy and safety of transcatheter aortic valve implantation in patients with BAV.

Methods and Results—

Of 470 patients included in our prospective transcatheter aortic valve implantation database (October 2006–January 2012), 229 consecutive patients undergoing both echocardiography and multidetector computed tomography were analyzed. We compared clinical outcomes in patients with vs patients without BAV. In this series of 229 patients, BAV was detected by multidetector computed tomography in 21 patients (9.2%). BAV was identified by transthoracic and transoesophagal echocardiography in only 9 of these 21 patients. Patients were 83.1±6.6 years old, and European system for cardiac operative risk evaluation score was 20.0%±11.4%. The BAV group was similar to the non-BAV group except for diabetes mellitus (4.8% vs 24.0%;
P
=0.05). The aortic annulus diameter in BAV patients was not significantly larger by multidetector computed tomography (24.7±3.0 vs 23.7±1.9 mm;
P
=0.07). The CoreValve was used more frequently in the BAV group (47.6% vs 16.3%;
P
=0.002). There was no significant difference in device success (100% vs 92.8%;
P
=0.37), risk of annulus rupture (0% vs 1.4%;
P
=1.00), or valve migration (0% vs 1.4%;
P
=1.00) in BAV patients compared with non-BAV patients. Postprocedural mean gradient (10.0±3.4 vs 9.7±4.1 mm Hg;
P
=0.58), aortic regurgitation ≥2 of 4 (19.0% vs 14.9%;
P
=0.54), 30-day mortality (4.8% vs 8.2%;
P
=1.00), and 30-day combined safety end point (14.3% vs 13.5%;
P
=1.00) were also similar in both groups.

Conclusions—
In selected BAV patients, transcatheter aortic valve implantation may be associated with low complication rate, efficacy, and acceptable outcomes similar to those in non-BAV patients.
Feasibility and Utility of Screening for Depression and Anxiety Disorders in Patients With Cardiovascular Disease
Authors: Celano Christopher M. , Suarez Laura , Mastromauro Carol , Januzzi James L. , Huffman Jeff C. 
Published: June 2013

Background—
Depression and anxiety in patients with cardiac disease are common and independently associated with morbidity and mortality. We aimed to explore the use of a 3-step approach to identify inpatients with cardiac disease with depression, generalized anxiety disorder (GAD), or panic disorder; understand the predictive value of individual screening items in identifying these disorders; and assess the relative prevalence of these disorders in this cohort.

Methods and Results—

To identify depression and anxiety disorders in inpatients with cardiac disease as part of a care management trial, an iterative 3-step screening procedure was used. This included an existing 4-item (Coping Screen) tool in nursing data sets, a 5-item screen for positive Coping Screen patients (Patient Health Questionnaire-2 [PHQ-2], GAD-2, and an item about panic attacks), and a diagnostic evaluation using PHQ-9 and the Primary Care Evaluation of Mental Disorders anxiety disorder modules. Overall, 6210 inpatients received the Coping Screen, 581 completed portions of all 3 evaluation steps, and 210 received a diagnosis (143 depression, 129 GAD, 30 panic disorder). Controlling for age, sex, and the other screening items, PHQ-2 items independently predicted depression (little interest/pleasure: odds ratio [OR]=6.65,
P
<0.001; depression: OR=5.24,
P
=0.001), GAD-2 items predicted GAD (anxious: OR=4.09,
P
=0.003; unable to control worrying: OR=10.46,
P
<0.001), and the panic item predicted panic disorder (OR=49.61,
P
<0.001).

Conclusions—
GAD was nearly as prevalent as depression in this cohort, and GAD-2 was an effective screening tool; however, panic disorder was rare. These results support the use of 2-step screening for depression and GAD beginning with a 4-item scale (GAD-2 plus PHQ-2).

Clinical Trial Registration—

Unique Identifier: NCT01201967. URL:
http://www.clinicaltrials.gov/ct2/show/NCT01201967
.
Risks and Benefits of Anticoagulation in Atrial Fibrillation
Authors: Cullen Michael W. , Kim Sunghee , Piccini Jonathan P. , Ansell Jack E. , Fonarow Greg C. , Hylek Elaine M. , Singer Daniel E. , Mahaffey Kenneth W. , Kowey Peter R. , Thomas Laine , Go Alan S. , Lopes Renato D. , Chang Paul , Peterson Eric D. , Gersh Bernard J. 
Published: June 2013

Background—
Patients with atrial fibrillation (AF) at the highest stroke risk derive the largest benefit from oral anticoagulation (OAC). Those with the highest stroke risk have been paradoxically less likely to receive OAC. This study assessed the association between stroke and bleeding risk on rates of OAC.

Methods and Results—

We analyzed OAC use among 10 098 patients with AF from 174 community-based outpatient practices enrolled in 2010–2011 in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). OAC was defined as warfarin or dabigatran use at study enrollment. Stroke and bleeding risk were calculated using congestive heart failure, hypertension, age, diabetes mellitus, prior stroke (CHADS
2
), and anticoagulation and risk factors in AF (ATRIA) scores, respectively. The mean subject age was 73 years; 58% were men. Overall, 76% of patients received OAC (71% warfarin and 5% dabigatran). The use of OAC increased among those with higher CHADS
2
scores, from 53% for CHADS
2
=0 to 80% for CHADS
2
≥2 (
P
<0.001). OAC use fell slightly with increasing ATRIA bleeding risk score, from 81% for ATRIA=3 to 73% for ATRIA≥5 (
P
<0.001). A significant interaction existed between ATRIA and CHADS
2
scores (
P
=0.021). Among those with low bleeding risk, use of OAC increased significantly with increasing stroke risk. Among those with high bleeding risk, CHADS
2
stroke risk had a smaller impact on use of OAC.

Conclusions—
In community-based outpatients with AF, use of OAC was high and driven by not only predominantly stroke but also bleeding risk. Stroke risk significantly affects OAC use among those with low bleeding risk, whereas those with high bleeding risk demonstrate consistently lower use of OAC regardless of stroke risk.
Intracoronary Delivery of Autologous Cardiac Stem Cells Improves Cardiac Function in a Porcine Model of Chronic Ischemic Cardiomyopathy
Authors: Bolli Roberto , Tang Xian-Liang , Sanganalmath Santosh K. , Rimoldi Ornella , Mosna Federico , Abdel-Latif Ahmed , Jneid Hani , Rota Marcello , Leri Annarosa , Kajstura Jan 
Published: June 2013

Background—
Relevant preclinical models are necessary for further mechanistic and translational studies of c-kit+ cardiac stem cells (CSCs). The present study was undertaken to determine whether intracoronary CSCs are beneficial in a porcine model of chronic ischemic cardiomyopathy.

Methods and Results—

Pigs underwent a 90-minute coronary occlusion followed by reperfusion. Three months later, autologous CSCs (n=11) or vehicle (n=10) were infused into the infarct-related artery. At this time, all indices of left ventricular (LV) function were similar in control and CSC-treated pigs, indicating that the damage inflicted by the infarct in the 2 groups was similar; 1 month later, however, CSC-treated pigs exhibited significantly greater LV ejection fraction (echocardiography) (51.7±2.0% versus 42.9±2.3%,
P
<0.01), systolic thickening fraction in the infarcted LV wall, and maximum LV dP/dt, as well as lower LV end-diastolic pressure. Confocal microscopy showed clusters of small α-sarcomeric actin–positive cells expressing Ki67 in the scar of treated pigs, consistent with cardiac regeneration. The origin of these cycling myocytes from the injected cells was confirmed in 4 pigs that received enhanced green fluorescent protein –labeled CSCs, which were positive for the cardiac markers troponin I, troponin T, myosin heavy chain, and connexin-43. Some engrafted CSCs also formed vascular structures and expressed α-smooth muscle actin.

Conclusions—
Intracoronary infusion of autologous CSCs improves regional and global LV function and promotes cardiac and vascular regeneration in pigs with old myocardial infarction (scar). The results mimic those recently reported in humans (Stem Cell Infusion in Patients with Ischemic CardiOmyopathy [SCIPIO] trial) and establish this porcine model of ischemic cardiomyopathy as a useful and clinically relevant model for studying CSCs.
An Engineered Bivalent Neuregulin Protects Against Doxorubicin-Induced Cardiotoxicity With Reduced Proneoplastic Potential
Authors: Jay Steven M. , Murthy Ashwin C. , Hawkins Jessica F. , Wortzel Joshua R. , Steinhauser Matthew L. , Alvarez Luis M. , Gannon Joseph , Macrae Calum A. , Griffith Linda G. , Lee Richard T. 
Published: June 2013

Background—
Doxorubicin (DOXO) is an effective anthracycline chemotherapeutic, but its use is limited by cumulative dose-dependent cardiotoxicity. Neuregulin-1β is an ErbB receptor family ligand that is effective against DOXO-induced cardiomyopathy in experimental models but is also proneoplastic. We previously showed that an engineered bivalent neuregulin-1β (NN) has reduced proneoplastic potential in comparison with the epidermal growth factor–like domain of neuregulin-1β (NRG), an effect mediated by receptor biasing toward ErbB3 homotypic interactions uncommonly formed by native neuregulin-1β. Here, we hypothesized that a newly formulated, covalent NN would be cardioprotective with reduced proneoplastic effects in comparison with NRG.

Methods and Results—

NN was expressed as a maltose-binding protein fusion in
Escherichia coli
. As established previously, NN stimulated antineoplastic or cytostatic signaling and phenotype in cancer cells, whereas NRG stimulated proneoplastic signaling and phenotype. In neonatal rat cardiomyocytes, NN and NRG induced similar downstream signaling. NN, like NRG, attenuated the double-stranded DNA breaks associated with DOXO exposure in neonatal rat cardiomyocytes and human cardiomyocytes derived from induced pluripotent stem cells. NN treatment significantly attenuated DOXO-induced decrease in fractional shortening as measured by blinded echocardiography in mice in a chronic cardiomyopathy model (57.7±0.6% versus 50.9±2.6%,
P
=0.004), whereas native NRG had no significant effect (49.4±3.7% versus 50.9±2.6%,
P
=0.813).

Conclusions—
NN is a cardioprotective agent that promotes cardiomyocyte survival and improves cardiac function in DOXO-induced cardiotoxicity. Given the reduced proneoplastic potential of NN versus NRG, NN has translational potential for cardioprotection in patients with cancer receiving anthracyclines.
Urgent Best Medical Therapy May Obviate the Need for Urgent Surgery in Patients With Symptomatic Carotid Stenosis
Authors: Shahidi Saeid , Owen-Falkenberg Alan , Hjerpsted Ulrik , Rai Amrit , Ellemann Karsten 
Published: June 2013

Background and Purpose—
The purpose of this study was to analyze the 30-day outcome after introduction of a rapid carotid endarterectomy (CEA) program. Reasons for delay in CEA and the incidence of early recurrence neurological symptoms were recorded.

Methods—
This is a prospective population-based study of delays to CEA and 30-day outcome in patients with symptomatic carotid stenosis. Neurological recurrence (NR) rate was determined after initiation of urgent best medical treatment (loading dose aspirin/clopidogrel and duel therapy with aspirin plus clopidogrel with a statin) until CEA and compared with NR ≤90 days prior index event.

Results—

Of a total of 4905 (transient ischemic attack/ischemic stroke, and ocular events) patients, 115 symptomatic patients underwent CEA, 42% within 14 days of the index event and 99% within 14 days of surgical referral. The overall NR from index event to CEA in symptomatic carotid stenosis patients was significantly lower (2.5% [95% confidence interval, 1%–6%]) after best medical treatment when compared with NR ≤90 days in those before referral to a stroke clinic (29% [95% confidence interval, 22%–37%];
P
<0.00001). There were no significant differences in outcomes among 48 early (<14 days), 46 intermediate (14–30 days), and 21 delayed (>30 days) CEAs.

Conclusions—
CEA can be performed in the subacute period without significantly increasing the operative risk. The urgent best medical treatment was associated with significant reduction in the risk of early NR in CEA patients. It seems that urgent aggressive best medical treatment may obviate the need for urgent CEA.
Impact of Diffusion-Weighted Imaging Lesion Volume on the Success of Endovascular Reperfusion Therapy
Authors: Olivot Jean-Marc , Mosimann Pascal J. , Labreuche Julien , Inoue Manabu , Meseguer Elena , Desilles Jean-Philippe , Rouchaud Aymeric , Klein Isabelle F. , Straka Matus , Bammer Roland , Mlynash Michael , Amarenco Pierre , Albers Gregory W. , Mazighi Mikael 
Published: June 2013

Background and Purpose—
Diffusion-weighted imaging (DWI) lesion volume is associated with poor outcome after thrombolysis, and it is unclear whether endovascular therapies are beneficial for large DWI lesion. Our aim was to assess the impact of pretreatment DWI lesion volume on outcomes after endovascular therapy, with a special emphasis on patients with complete recanalization.

Methods—
We analyzed data collected between April 2007 and November 2011 in a prospective clinical registry. All acute ischemic stroke patients with complete occlusion of internal carotid artery or middle cerebral artery treated by endovascular therapy were included. DWI lesion volumes were measured by the RAPID software. Favorable outcome was defined by modified Rankin Scale of 0 to 2 at 90 days.

Results—

A total of 139 acute ischemic stroke patients were included. Median DWI lesion volume was 14 cc (interquartile range, 5–43) after a median onset time to imaging of 110 minutes (interquartile range, 77–178). Higher volume was associated with less favorable outcome (adjusted odds ratio, 0.55; 95% confidence interval, 0.31–0.96). A complete recanalization was achieved in 65 (47%) patients after a median onset time of 238 minutes (interquartile range, 206–285). After adjustment for volume, complete recanalization was associated with more favorable outcome (adjusted odds ratio, 6.32; 95% confidence interval, 2.90–13.78). After stratification of volume by tertiles, complete recanalization was similarly associated with favorable outcome in the upper 2 tertiles (
P
<0.005).

Conclusions—
Our results emphasize the importance of initial DWI volume and recanalization on clinical outcome after endovascular treatment. Large DWI lesions may still benefit from recanalization in selected patients.
Protamine Does Not Increase Risk of Stroke in Patients With Elective Carotid Stenting
Authors: McDonald Jennifer S. , Kallmes David F. , Lanzino Giuseppe , Cloft Harry J. 
Published: June 2013

Background and Purpose—
Reversal of anticoagulation with protamine might predispose to a higher risk of stroke in patients with carotid stenting. We evaluated a national, multihospital patient database to examine the risk of stroke in patients with carotid stenting receiving protamine compared with those who did not.

Methods—
The Premier Perspective database was used to identify patients who were electively hospitalized for carotid stenting from 2006 through 2011. The incidence of in-hospital mortality and morbidity was compared between patients who did and did not receive protamine after propensity score adjustment via 1:1 matching to reduce selection bias.

Results—

Of 6664 patients with carotid stenting treated at 193 hospitals, 556 (8%) received protamine on the day of the procedure. After matching by propensity score, patients who received protamine had a similar likelihood of stroke or transient ischemic attack (
P
=0.77), in-hospital mortality (
P
=0.12), discharge to long-term care (
P
=0.15), and access site complications (
P
=0.90) as compared with patients who did not receive protamine.

Conclusions—
Protamine administration is not associated with additional risk of adverse events after carotid stenting.
Geographic and Sex Difference in the Distribution of Intracranial Atherosclerosis in China
Authors: Pu Yuehua , Liu Liping , Wang Yilong , Zou Xinying , Pan Yuesong , Soo Yannie , Leung Thomas , Zhao Xingquan , Wong Ka Sing , Wang Yongjun 
Published: June 2013

Background and Purpose—
Geographic variation and sex difference in the distribution of intracranial atherosclerosis (ICAS) have not been fully discussed before in Chinese patients with cerebral ischemia. We performed this study with the aim to investigate geographic and sex difference in the distribution of ICAS in China.

Methods—
In this prospective multicenter study, we evaluated 2864 consecutive patients who experienced an acute cerebral ischemia within 7 days of symptom onset in 22 hospitals in China. All the inclusive patients underwent 3-dimensional time-of-flight MR angiography and duplex color Doppler ultrasound or contrast-enhanced MR angiography to document the presence of intracranial or extracranial stenosis. Intracranial large-artery atherosclerosis was defined as ≥50% diameter reduction on MR angiography.

Results—

The proportion of patients with ICAS was significantly higher in north China than in south China (50.22% versus 41.88%;
P
<0.0001). Patients in the north were likely to consume more alcohol and smoke more cigarettes and had significantly higher proportion of diabetes mellitus, family history of stroke, history of cerebral ischemia, heart disease, and higher body mass index. In patients aged >63 years, the percentage of ICAS in women was notably higher than in men (51.51% versus 45.40%;
P
=0.028). In elderly patients, women had higher proportion of diabetes mellitus, hypertension, hyperlipidemia, and heart disease than men.

Conclusions—
There exists geographic and sex difference in the distribution of symptomatic ICAS in China. Public health measures should strengthen improving social determinants of health and risk factor prevention/control in high-risk populations for decreasing stroke risk.
Homocysteine Improves Risk Stratification in Patients Undergoing Endarterectomy for Asymptomatic Internal Carotid Artery Stenosis
Authors: Duschek Nikolaus , Ghai Samarth , Sejkic Fahrudin , Falkensammer Jürgen , Skrinjar Edda , Huber Kurt , Wojta Johann , Waldhör Thomas , Hübl Wolfgang , Assadian Afshin 
Published: June 2013

Background and Purpose—
A limited life expectancy reduces the benefit from carotid endarterectomy (CEA) for treatment of asymptomatic internal carotid artery stenosis. The aim of this study was to assess homocysteine as stratifying biomarker to improve prediction of postoperative survival.

Methods—
This was a single-center cohort study from 2003 to 2012. Two hundred and fourteen consecutive patients (<75 years, n=130; ≥75 years, n=84) undergoing CEA for their asymptomatic internal carotid artery stenosis were observed for 8.5 years for the occurrence of death after CEA as primary end point (EC-nr: 04-067-0604). Homocysteine and major cardiovascular risk factors were used for computation of prognostic indices. Cumulative survival of prognostic indices–based quintiles was estimated by Kaplan–Meier curves.

Results—

Total homocysteine had a significant effect on postoperative survival (
P
<0.0001). Total homocysteine–based quintiles of prognostic indices showed a better prediction of the survival of the patients than age alone. This caused reclassification of 17 patients (20.2%) >75 years as fit for surgery, but also indicated a high risk for 19 patients (14.6%) <75 years. In the majority (79.8%) of patients aged >75 years, statistically, CEA could not be advised because of a significantly reduced 5-year survival rate.

Conclusions—
High plasma homocysteine levels suggest that older patients with asymptomatic carotid stenosis might rather benefit from intensive medical therapy than from CEA.
Association of Prestroke Statin Use and Lipid Levels With Outcome of Intracerebral Hemorrhage
Authors: Mustanoja Satu , Strbian Daniel , Putaala Jukka , Meretoja Atte , Curtze Sami , Haapaniemi Elena , Sairanen Tiina , Hietikko Ronja , Sirén Joonas , Kaste Markku , Tatlisumak Turgut 
Published: June 2013

Background and Purpose—
It is unclear whether blood lipid profiles and statin use before intracerebral hemorrhage (ICH) are associated with its outcome.

Methods—
The Helsinki ICH Study, a single-center observational registry of consecutive ICH patients, was used to study the associations between premorbid statin use, baseline lipid levels, and clinical outcome.

Results—

The registry includes 964 ICH patients. Statin users (n=187; 19%) were significantly older, had more frequent comorbidities and medication, lower lipid levels, and higher admission Glasgow Coma Scale compared with nonusers. Modified Rankin Scale at discharge or mortality did not differ between statin users and nonusers. Compared with survivors, significantly lower total cholesterol and low-density lipoprotein cholesterol levels were observed in patients who died in hospital (median, 4.1 mmol/L [interquartile range, 3.6–4.4] versus 4.5 [3.8–5.1];
P
<0.01; 1.9 mmol/L [1.4–2.5] versus 2.4 [1.8–3.0];
P
<0.001, respectively), at 3 or 12 months. After adjusting for known ICH prognostic factors based on univariate analysis that is, age, National Institutes of Health Stroke Scale, Glasgow Coma Scale, ICH volume, and intraventricular location, lower low-density lipoprotein levels were independently associated with in-hospital mortality (odds ratio, 0.54 [95% confidence interval, 0.31–0.93];
P
=0.028).

Conclusions—
Premorbid statin use did not affect the outcome of ICH, but lower low-density lipoprotein levels were associated with higher in-hospital mortality.