bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-148b Functions as a Tumor Suppressor in Pancreatic Cancer by Targeting AMPKα1
Authors: Zhao Gang , Zhang Jun-Gang , Liu Yang , Qin Qi , Wang Bo , Tian Kui , Liu Lin , Li Xiang , Niu Yi , Deng Shi-Chang , Wang Chun-You 
Published: November 2012

Abstract
miRNAs are small noncoding RNAs that participate in a variety of biologic processes, and dysregulation of miRNA is always associated with cancer development and progression. Aberrant expression of miR-148b has been found in some types of cancer, but its expression and potential biologic role in pancreatic cancer are still largely unknown. In this study, our data showed that miR-148b was significantly downregulated in 48 pairs of human pancreatic cancer tissues and five cell lines. Furthermore, the deregulated miR-148b was correlated with increased tumor size, late tumor–node–metastasis stage, lymphatic invasion, distant metastasis, and worse prognosis in pancreatic cancer. Functional studies indicated overexpression of miR-148b dramatically suppressed the growth of cancer cells, attributable to induction of apoptosis and cell-cycle arrest at S-phase. Meanwhile, miR-148b remarkably inhibited invasion and enhanced chemosensitivity of pancreatic cancer cells. Moreover, ectopic expression of miR-148b was able to inhibit tumorigenicity in nude mice. Further studies revealed that AMPKα1 might be the direct target gene of miR-148b, and overexpressed AMPKα1 inversely correlated with miR-148b in pancreatic cancer. Silencing of AMPKα1 with RNA interference inhibited the growth of pancreatic cancer cells in vitro and in vivo and also induced apoptosis, cell-cycle arrest, and inhibited invasion of cancer cells, which is consistent with the effects of miR-148b overexpression. In conclusion, miR-148b can inhibit cell proliferation, invasion, and enhance chemosensitivity of pancreatic cancer by targeting AMPKα1. Our present results implicate the potential effects of miR-148b on prognosis and treatment of pancreatic cancer. Mol Cancer Ther; 12(1); 83–93. ©2012 AACR.
Predictors of Clinical Outcomes in Patients With Severe Aortic Stenosis Undergoing TAVI
Authors: Pilgrim Thomas , Kalesan Bindu , Wenaweser Peter , Huber Christoph , Stortecky Stefan , Buellesfeld Lutz , Khattab Ahmed A. , Eberle Balthasar , Gloekler Steffen , Gsponer Thomas , Meier Bernhard , Jüni Peter , Carrel Thierry , Windecker Stephan 
Published: November 2012

Background—
Patients with severe aortic stenosis at increased surgical risk continue to experience compromised long-term survival despite successful transcatheter aortic valve implantation. We used time-related pathways in a multistate analysis to identify predictors of adverse long-term outcome in patients who underwent transcatheter aortic valve implantation.

Methods and Results—

In a cohort of 389 patients with a mean age of 82.4±5.8 years and a STS score of 6.8±5.3 undergoing transcatheter aortic valve implantation between 2007 and 2011, multistate analysis was used to estimate mortality and stroke taking into account intercurrent events including kidney injury and the composite of access site and bleeding complications (ABC). Transapical access emerged as a predictor of kidney injury (hazard ratio [HR], 2.12; 95% confidence interval [CI] 1.00–4.47) and ABC (HR, 1.78; 95% CI, 1.07–2.96), but had no impact on the risk of stroke or death. Body mass index ≤20 kg/m
2
increased the risk of stroke or death (HR, 2.64; 95% CI, 1.25–5.54). Age >80 years (HR, 3.15; 95% CI, 1.11–8.92), body mass index ≤20 kg/m
2
(HR, 4.11; 95% CI, 1.33–12.70), prior stroke (HR, 16.42; 95% CI, 3.63–74.21), and presence of atrial fibrillation at baseline (HR, 4.12; 95% CI, 1.87–9.97) increased the risk of stroke and death after an intercurrent event of ABC.

Conclusions—

A body mass index ≤20 kg/m
2
was identified as a primary predictor of stroke and death after transcatheter aortic valve implantation during long-term follow-up, whereas transapical access emerged as a predictor of kidney injury and ABC. Age >80 years, body mass index ≤20 kg/m
2
, prior stroke, and presence of atrial fibrillation at baseline increased the risk of stroke and death after an intercurrent event of ABC.
Stroke After Carotid Stenting and Endarterectomy in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)
Authors: Hill Michael D. , Brooks William , Mackey Ariane , Clark Wayne M. , Meschia James F. , Morrish William F. , Mohr J.P. , Rhodes J. David , Popma Jeffrey J. , Lal Brajesh K. , Longbottom Mary E. , Voeks Jenifer H. , Howard George , Brott Thomas G. ,   for the CREST Investigators
Published: November 2012

Background—
Stroke occurs more commonly after carotid artery stenting than after carotid endarterectomy. Details regarding stroke type, severity, and characteristics have not been reported previously. We describe the strokes that have occurred in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).

Methods and Results—
CREST is a randomized, open-allocation, controlled trial with blinded end-point adjudication. Stroke was a component of the primary composite outcome. Patients who received their assigned treatment within 30 days of randomization were included. Stroke was adjudicated by a panel of board-certified vascular neurologists with secondary central review of clinically obtained brain images. Stroke type, laterality, timing, and outcome were reported. A periprocedural stroke occurred among 81 of the 2502 patients randomized and among 69 of the 2272 in the present analysis. Strokes were predominantly minor (81%, n=56), ischemic (90%, n=62), in the anterior circulation (94%, n=65), and ipsilateral to the treated artery (88%, n=61). There were 7 hemorrhages, which occurred 3 to 21 days after the procedure, and 5 were fatal. Major stroke occurred in 13 (0.6%) of the 2272 patients. The estimated 4-year mortality after stroke was 21.1% compared with 11.6% for those without stroke. The adjusted risk of death at 4 years was higher after periprocedural stroke (hazard ratio, 2.78; 95% confidence interval, 1.63–4.76).

Conclusions—
Stroke, particularly severe stroke, was uncommon after carotid intervention in CREST, but stroke was associated with significant morbidity and was independently associated with a nearly 3-fold increased future mortality. The delayed timing of major and hemorrhagic stroke after revascularization suggests that these strokes may be preventable.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00004732.
Sprint Fidelis Lead Fractures in Patients With Cardiac Resynchronization Therapy Devices
Authors: Parkash Ratika , Thibault Bernard , Sterns Larry , Sapp John , Krahn Andrew , Talajic Mario , Luce Marilynn , Yetisir Elizabeth , Theoret-Patrick Patricia , Wells George , Tang Anthony 
Published: November 2012

Background—
Using data from the Resynchronization/Defibrillation for Ambulatory Heart Failure (RAFT) study, we examined whether Fidelis lead failure was more common in patients with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (ICD-CRT) than in patients with an ICD only.

Methods and Results—

All cases of patients who had a right ventricular defibrillation lead revision in the RAFT study were adjudicated for the presence of lead fracture. Criteria for fracture were at least 2 of the following: (1) Impedance rise (>50% or >500 Ω in 1 week), (2) short interval count >10 times per day or 300 times per month, or (3) inappropriate shock caused by noise, verified by stored electrogram. A total of 1798 patients were enrolled into the RAFT study, with a mean follow-up of 40±20 months. There were 818 patients (45.5%) who received a Fidelis lead at the original implantation, 405 with an ICD only and 413 with an ICD-CRT. There were 47 confirmed defibrillation lead fractures; 45 were Fidelis leads (5.5% of Fidelis leads). The overall rate of fracture in the ICD group was 3.2% compared with 7.8% in the ICD-CRT group (
P
=0.006; hazard ratio, 2.42; 95% confidence interval, 1.27–4.61). Significant correlates of lead fracture in this population were undergoing an ICD-CRT implantation and having ≥2 leads.

Conclusions—
In this analysis of the RAFT study, patients with an ICD-CRT were found to have a significantly higher fracture rate than patients with an ICD. This finding needs to be considered when these patients are assessed for possible lead revision at the time of an elective generator replacement.
Associations of Total and High-Molecular-Weight Adiponectin With All-Cause and Cardiovascular Mortality in Older Persons
Authors: Kizer Jorge R. , Benkeser David , Arnold Alice M. , Mukamal Kenneth J. , Ix Joachim H. , Zieman Susan J. , Siscovick David S. , Tracy Russell P. , Mantzoros Christos S. , deFilippi Christopher R. , Newman Anne B. , Djousse Luc 
Published: November 2012

Background—
Adiponectin shows opposite associations with adverse outcomes in healthy middle-aged populations (lower risk) and cohorts with prevalent cardiovascular disease, heart failure, or advanced age (higher risk).

Methods and Results—
In a population-based study of older adults, we examined the relationships of total and high-molecular-weight adiponectin with mortality among subgroups defined by baseline cardiovascular status: No cardiovascular disease, heart failure, or atrial fibrillation (group 1); cardiovascular disease but no heart failure/atrial fibrillation (group 2); and heart failure/atrial fibrillation (group 3). We found significant differences in the associations with all-cause mortality across the groups. The association in group 1 was U-shaped; increasing levels of total adiponectin up to 12.4 mg/L were associated with lower mortality after adjustment for confounders (hazard ratio=0.81 per 1 SD [95% confidence interval, 0.65–0.95]), but above this cut point, higher levels conferred greater risk (hazard ratio=1.19 [95% confidence interval, 1.12–1.27]). Further adjustment for diabetes mellitus or insulin resistance, protection against which has been proposed to mediate the beneficial relationships of adiponectin with outcome, attenuated the association in the lower range. There was no significant association in group 2, but in group 3, total adiponectin showed a direct adjusted association. Additional adjustment for putative metabolic/inflammatory intermediates suggested a direct association for group 2, and magnified the one for group 3 (hazard ratio=1.31 [1.15–1.50]). Results were similar for high-molecular-weight adiponectin and for cardiovascular mortality.

Conclusions—
Adiponectin exhibits distinct associations with mortality in elders, which shift from U-shaped to flat to direct with greater baseline cardiovascular dysfunction but become more consistently adverse after accounting for metabolic/inflammatory factors presumed to be favorably regulated by the adipokine. These findings advance understanding of the adiponectin paradox as it relates to older adults.
A Population-Based Study of Hospital Care Costs During 5 Years After Transient Ischemic Attack and Stroke
Authors: Luengo-Fernandez Ramon , Gray Alastair M. , Rothwell Peter M. 
Published: November 2012

Background and Purpose—
Few studies have evaluated long-term costs after stroke onset, with almost no cost data for transient ischemic attack (TIA). We studied hospital costs during the 5 years after TIA or stroke in a population-based study.

Methods—
Patients from a United Kingdom population-based cohort study (Oxford Vascular Study) were recruited from 2002 to 2007. Analysis was based on follow-up until 2010. Hospital resource usage was obtained from patient hospital records and valued using 2008/2009 unit costs. Because not all patients had full 5-year follow-up, we used nonparametric censoring techniques.

Results—
Among 485 TIA and 729 stroke patients ascertained and included, mean censor-adjusted 5-year hospital costs after index stroke were $25741 (95% confidence interval, 23659–27914), with costs varying considerably by severity: $21134 after minor stroke; $33119 after moderate stroke; and $28552 after severe stroke. For the 239 surviving stroke patients who had reached final follow-up, mean costs were $24383 (95% confidence interval, 20156–28595), with more than half of costs ($12972) being incurred in the first year after the event. After index TIA, the mean censor-adjusted 5-year costs were $18091 (95% confidence interval, 15947–20258). A multivariate analysis showed that event severity, recurrent stroke, and coronary events after the index event were independent predictors of 5-year costs. Differences by stroke subtype were mostly explained by stroke severity and subsequent events.

Conclusions—
Long-term hospital costs after TIA and stroke are considerable, but they are mainly incurred during the first year after the index event. Event severity and experiencing subsequent stroke and coronary events after the index event accounted for much of the increase in costs.
Trends in Substance Abuse Preceding Stroke Among Young Adults
Authors: de los Ríos Felipe , Kleindorfer Dawn O. , Khoury Jane , Broderick Joseph P. , Moomaw Charles J. , Adeoye Opeolu , Flaherty Matthew L. , Khatri Pooja , Woo Daniel , Alwell Kathleen , Eilerman Jane , Ferioli Simona , Kissela Brett M. 
Published: November 2012

Background and Purpose—
Approximately 5% of strokes occur in adults aged 18 to 44 years. Substance abuse is a prevalent risk factor for stroke in young adults. We sought to identify trends in substance abuse detection among stroke patients.

Methods—
Using a population-based design, we sought to identify all patients aged 18 to 54 years experiencing a stroke (ischemic or hemorrhagic) in the Greater Cincinnati and Northern Kentucky Study region during 1993 to 1994, 1999, and 2005. Demographic and clinical characteristics and substance use data were obtained retrospectively from chart review and adjudicated by physicians.

Results—

The number of young patients identified with a stroke increased from 1993 to 1994 (297) to 2005 (501). Blacks (61% vs 51%;
P
<0.02) and men (61% vs 47%;
P
<0.002) reported substance abuse (current smoking, alcohol, or illegal drug use) more frequently than did whites and women. Overall use of substances increased across study periods, 45% in 1993 versus 62% in 2005 (
P
=0.003). The trend was significant for illegal drug use (3.8% in 1993 vs 19.8% in 2005) and ever smoking (49% in 1993 vs 66% in 2005). Documentation of both cocaine and marijuana use increased over time. In 2005, half of young adults with a stroke were current smokers, and 1 in 5 abused illegal drugs.

Conclusions—
Substance abuse is common in young adults experiencing a stroke. The observed increase in substance abuse is contributing to the increased incidence of stroke in young adults. Patients aged younger than 55 years who experience a stroke should be routinely screened and counseled regarding substance abuse.
Reliability of Real-Time Video Smartphone for Assessing National Institutes of Health Stroke Scale Scores in Acute Stroke Patients
Authors: Demaerschalk Bart M. , Vegunta Sravanthi , Vargas Bert B. , Wu Qing , Channer Dwight D. , Hentz Joseph G. 
Published: November 2012

Background and Purpose—
Telestroke reduces acute stroke care disparities between urban stroke centers and rural hospitals. Current technologies used to conduct remote patient assessments have high start-up costs, yet they cannot consistently establish quality timely connections. Smartphones can be used for high-quality video teleconferencing. They are inexpensive and ubiquitous among health care providers. We aimed to study the reliability of high-quality video teleconferencing using smartphones for conducting the National Institutes of Health Stroke Scale (NIHSS).

Methods—
Two vascular neurologists assessed 100 stroke patients with the NIHSS. The remote vascular neurologist assessed subjects using smartphone videoconferencing with the assistance of a bedside medical aide. The bedside vascular neurologist scored patients contemporaneously. Each vascular neurologist was blinded to the other’s NIHSS scores. We tested the inter-method agreement and physician satisfaction with the device.

Results—

We demonstrated high total NIHSS score correlation between the methods (
r
=0.949;
P
<0.001). The mean total NIHSS scores for bedside and remote assessments were 7.93±8.10 and 7.28±7.85, with ranges, of 0 to 35 and 0 to 37, respectively. Eight categories had high agreement: level of consciousness (questions), level of consciousness (commands), visual fields, motor left and right (arm and leg), and best language. Six categories had moderate agreement: level of consciousness (consciousness), best gaze, facial palsy, sensory, dysarthria, and extinction/inattention. Ataxia had poor agreement. There was high physician satisfaction with the smartphone.

Conclusions—
Smartphone high-quality video teleconferencing is reliable, easy to use, affordable for telestroke NIHSS administration, and has high physician satisfaction.
Risk of Intracranial Hemorrhage With Protease-Activated Receptor-1 Antagonists
Authors: Lee Meng , Saver Jeffrey L. , Hong Keun-Sik , Wu Hsiu-Chuan , Ovbiagele Bruce 
Published: November 2012

Background and Purpose—
Recent clinical trial data suggest that protease-activated receptor-1 (PAR-1) antagonists may increase the risk of intracranial hemorrhage. Our objective was to investigate the qualitative and quantitative risks of intracranial hemorrhage in patients receiving PAR-1 antagonist therapy.

Methods—

Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov from 1966 to May 2012, were searched to identify relevant studies. We included randomized controlled trials that included a comparison of PAR-1 antagonist with placebo and in which the total number of patients and intracranial hemorrhage events were reported separately for active treatment and control groups. Summary incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using random-effects models. Between-study heterogeneity was assessed using the
I
2
statistic.

Results—

In 9 PAR-1 antagonist trials with 42000 patients with a history of thrombotic vascular disease or acute coronary syndrome, PAR-1 antagonist treatment was associated with increased risk of intracranial hemorrhage (0.59% vs 0.30%; relative risk, 1.98; 95% CI, 1.46–2.68;
P
<0.00001; number needed to harm, 345). There was no heterogeneity across trials (
P
=0.84;
I
2
=0%), PAR-1 antagonist agent (
P
=0.52), treatment duration (
P
=0.38), or trial-qualifying event (
P
=0.59). Risk of death from any cause or a cardiovascular cause did not differ between active treatment and control groups.

Conclusion—
In a pooled analysis of data from 9 trials, PAR-1 antagonist therapy was associated with an increased risk for intracranial hemorrhage.
Lower Susceptibility to Cerebral Small Vessel Disease in Human Familial Longevity
Authors: Altmann-Schneider Irmhild , van der Grond Jeroen , Slagboom P. Eline , Westendorp Rudi G.J. , Maier Andrea B. , van Buchem Mark A. , de Craen Anton J.M. 
Published: November 2012

Background and purpose—
On MRI, cerebral white matter lesions, lacunar infarcts, and cerebral microbleeds are common imaging correlates of cerebral small vessel damage in apparently healthy elderly individuals. We investigated whether middle-aged to elderly offspring of nonagenarian siblings, who are predisposed to become long-lived as well, have a lower prevalence of white matter lesions, lacunar infarcts, and cerebral microbleeds than control subjects.

Methods—
All subjects were from the Leiden Longevity Study. In this study, middle-aged to elderly offspring of nonagenarian siblings, who are predisposed to become long-lived as well, were contrasted to their spouses. Cerebral small vessel disease was assessed using 3-T MRI.

Results—

Offspring were less likely to have severe periventricular frontal caps (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1–1.1;
P
trend=0.01) and severe periventricular bands (OR, 0.4; 95% CI, 0.2–0.8;
P
trend=0.02). Moreover, offspring were less likely to have frontal (OR, 0.4; 95% CI, 0.2–0.9;
P
trend=0.05), parietal (OR, 0.4; 95% CI, 0.1–0.9;
P
trend=0.001), temporal (OR, 0.3; 95% CI, 0.1–0.8];
P
trend=0.004), and occipital subcortical white matter lesions (OR, 0.3; 95% CI, 0.1–0.6;
P
trend=0.001). Prevalence of lacunar infarcts also was lower in offspring (OR, 0.3; 95% CI, 0.1–1.1;
P
=0.07). Prevalence of microbleeds was not significantly different in offspring and control subjects.

Conclusions—
Exceptional familial longevity is associated with a lower susceptibility to white matter lesions and lacunar infarcts, but not cerebral microbleeds.
Final Infarct Volume Is a Stronger Predictor of Outcome Than Recanalization in Patients With Proximal Middle Cerebral Artery Occlusion Treated With Endovascular Therapy
Authors: Zaidi Syed F. , Aghaebrahim Amin , Urra Xabier , Jumaa Mouhammad A. , Jankowitz Brian , Hammer Maxim , Nogueira Raul , Horowitz Michael , Reddy Vivek , Jovin Tudor G. 
Published: November 2012

Background and Purpose—
The rationale for recanalization therapy in acute ischemic stroke is to preserve brain through penumbral salvage and thus improve clinical outcomes. We sought to determine the relationship between recanalization, clinical outcomes, and final infarct volumes in acute ischemic stroke patients presenting with middle cerebral artery occlusion who underwent endovascular therapy and post-procedure magnetic resonance imaging.

Methods—
We identified 201 patients with middle cerebral artery occlusion. Patients with other occlusive lesions were excluded. Baseline clinical/radiological characteristics, procedural outcomes (including thrombolysis in cerebral infarction scores), clinical outcome scores (modified Rankin scores), and final infarct volumes on diffusion weighted imaging were retrospectively analyzed from a prospectively collected database. Favorable outcome is defined as 90-day modified Rankin score ≤2.

Results—

Successful recanalization (thrombolysis in cerebral infarction grade 2b or 3) was achieved in 63.2% and favorable outcomes in 46% of cases. Mean infarct volume was 50.1 mL in recanalized versus 133.9 mL in non-recanalized patients (
P
<0.01) and 40.4 mL in patients with favorable outcomes versus 111.8 in patients with unfavorable outcomes (
P
<0.01). In multivariate analysis, thrombolysis in cerebral infarction ≥2b, baseline National Institute of Health Stroke Scale, Alberta Stroke Program Early Computed Tomography scores, and age were identified as independent predictors of outcome. However, when infarct volumes were included in the analysis only final infarct volume and age remained significantly associated.

Conclusions—
Successful recanalization leads to improved functional outcomes through a reduction in final infarct volumes. In our series, age and final infarct volume but not recanalization were found to be independent predictors of outcome, supporting the use of final infarct volume as surrogate marker of outcome in acute stroke trials.
Isolated Nondominant Right Coronary Stenosis
Authors: Ilia Reuben , Cafri Carlos , Wolak Arik , Weinstein Jean Marc 
Published: November 2012

The frequency, clinical presentation, and management of severely stenotic isolated nondominant right coronary artery (NDRCA) have not been adequately defined. We sought to do so in a large cohort of patients undergoing coronary angiography. We retrospectively analyzed all patients who underwent coronary angiography in our institute between 1995 and June 2012, looking at those with a severe lesion in the NDRCA, recording demographic, clinical, and angiographic data. Of the 43 327 patients, 35 (0.08%) were found to have a severely stenotic NDRCA as a single-vessel disease. The most common indication for catheterization was acute coronary syndrome (49%). Most of the patients were managed conservatively (66%) and the entire group had a relatively benign course, with no coronary deaths. Severe stenosis of the NDRCA as isolated disease is a very rare entity, and although most commonly presenting with acute coronary syndrome, conservative management was the usual approach.