bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel measures of left ventricular electromechanical discoordination predict clinical outcomes in children with pulmonary arterial hypertension
Authors: Frank Benjamin S. , Schäfer Michal , Douwes Johannes M. , Ivy D. Dunbar , Abman Steven H. , Davidson Jesse A. , Burzlaff Sandra , Mitchell Max B. , Morgan Gareth J. , Browne Lorna P. , Barker Alex J. , Truong Uyen , von Alvensleben Johannes C. 
Published: December 2019

Adverse ventricle-ventricle interaction and resultant left ventricular (LV) dysfunction are a recognized pathophysiological component of disease progression in pulmonary arterial hypertension (PAH) and can be associated with electrical and mechanical dyssynchrony. The purpose of this study was to investigate the clinical and mechanistic implications of LV electromechanical dyssynchrony in children with PAH by using novel systolic stretch and diastolic relaxation discoordination indexes derived noninvasively from cardiac MRI (CMR). In children with PAH referred for CMR ( n = 64) and healthy controls ( n = 20), we calculated two novel markers of ventricular discoordination, systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF). SSF and DRF were evaluated with respect to 1) electrical dyssynchrony, 2) functional status, and 3) composite clinical outcomes. SSF was increased in patients with PAH compared with controls ( P = 0.004). There was no difference in DRF between PAH and control groups. There were no differences between groups in standard mechanical dyssynchrony and LV global circumferential strain. Increased SSF was associated with greater electrical dyssynchrony (QRS duration) as well as worse WHO functional class. SSF, DRF, mechanical dyssynchrony, and right ventricular (RV) volumes were prognostic for worse clinical outcomes. LV dyssynchrony indexes are altered in pediatric patients with PAH compared with controls in proportion with greater degrees of RV dilation. Patients with PAH with greater dyssynchrony have worse clinical outcomes. RV-induced increased LV electromechanical dyssynchrony therefore may be an important link in the causal pathway from PAH to clinically significant LV dysfunction. Since dyssynchrony could precede overt LV dysfunction, addition of ventricular synchrony analysis to CMR postprocessing protocols may be of clinical benefit. NEW & NOTEWORTHY We demonstrate that left ventricular discoordination indexes are altered in pediatric patients with pulmonary arterial hypertension compared with controls and pediatric patients with pulmonary arterial hypertension with greater dyssynchrony have worse clinical outcomes. Furthermore, there is evidence for the mechanism of right ventricular-induced left ventricular discoordination to include a combination of delayed early systolic electromechanical activation, late-systolic septal shift, and prolonged, postsystolic septal thickening.
Rivaroxaban Reduces Arterial Thrombosis by Inhibition of FXa-Driven Platelet Activation via Protease Activated Receptor-1
Authors: Petzold Tobias , Thienel Manuela , Dannenberg Lisa , Mourikis Philipp , Helten Carolin , Ayhan Aysel , M’Pembele René , Achilles Alina , Trojovky Kajetan , Konsek Daniel , Zhang Zhe , Regenauer Ron , Pircher Joachim , Ehrlich Andreas , Lüsebrink Enzo , Nicolai Leo , Stocker Thomas J. , Brandl Richard , Röschenthaler Franz , Strecker Jan , Saleh Inas , Spannagl Michael , Mayr Christoph H. , Schiller Herbert B. , Jung Christian , Gerdes Norbert , Hoffmann Till , Levkau Bodo , Hohlfeld Thomas , Zeus Tobias , Schulz Christian , Kelm Malte , Polzin Amin 
Published: December 2019

Rationale:
A reduced rate of myocardial infarction has been reported in patients with atrial fibrillation treated with FXa (factor Xa) inhibitors including rivaroxaban compared with vitamin K antagonists. At the same time, low-dose rivaroxaban has been shown to reduce mortality and atherothrombotic events in patients with coronary artery disease. Yet, the mechanisms underlying this reduction remain unknown.

Objective:
In this study, we hypothesized that rivaroxaban’s antithrombotic potential is linked to a hitherto unknown rivaroxaban effect that impacts on platelet reactivity and arterial thrombosis.

Methods and Results:
In this study, we identified FXa as potent, direct agonist of the PAR-1 (protease-activated receptor 1), leading to platelet activation and thrombus formation, which can be inhibited by rivaroxaban. We found that rivaroxaban reduced arterial thrombus stability in a mouse model of arterial thrombosis using intravital microscopy. For in vitro studies, atrial fibrillation patients on permanent rivaroxaban treatment for stroke prevention, respective controls, and patients with new-onset atrial fibrillation before and after first intake of rivaroxaban (time series analysis) were recruited. Platelet aggregation responses, as well as thrombus formation under arterial flow conditions on collagen and atherosclerotic plaque material, were attenuated by rivaroxaban. We show that rivaroxaban’s antiplatelet effect is plasma dependent but independent of thrombin and rivaroxaban’s anticoagulatory capacity.

Conclusions:
Here, we identified FXa as potent platelet agonist that acts through PAR-1. Therefore, rivaroxaban exerts an antiplatelet effect that together with its well-known potent anticoagulatory capacity might lead to reduced frequency of atherothrombotic events and improved outcome in patients.
Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage
Authors: Kim Bum Joon , Kwon Sun U. , Park Joung-Ho , Kim Yong-Jae , Hong Keun-Sik , Wong Lawrence K.S. , Yu Sungwook , Hwang Yang-Ha , Lee Ji Sung , Lee Juneyoung , Rha Jong-Ho , Heo Sung Hyuk , Ahn Seong Hwan , Seo Woo-Keun , Park Jong-Moo , Lee Ju-Hun , Kwon Jee-Hyun , Sohn Sung-Il , Jung Jin-Man , Navarro Jose C. , Kim Hahn Young , Kim Eung-Gyu , Kim Seongheon , Cha Jae-Kwan , Park Man-Seok , Nam Hyo Suk , Kang Dong-Wha ,   on behalf of the PICASSO Investigators
Published: December 2019

Background and Purpose—
Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage).

Methods—
Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups.

Results—

Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke (
P
for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01–0.61];
P
=0.01). A marginal interaction between treatment group and white matter change on any stroke (
P
for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13–0.97];
P
=0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29–0.92];
P
=0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up.

Conclusions—
Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive.

Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01013532.
Higher Plaque Burden of Middle Cerebral Artery Is Associated With Recurrent Ischemic Stroke
Authors: Ran Yuncai , Wang Yuting , Zhu Ming , Wu Xiao , Malhotra Ajay , Lei Xiaowen , Zhang Feifei , Wang Xiao , Xie Shanshan , Zhou Jian , Zhu Jinxia , Cheng Jingliang , Zhu Chengcheng 
Published: December 2019

Background and Purpose—
This study aims to investigate the association between the characteristics of atherosclerotic plaques of middle cerebral artery and recurrent ischemic stroke using magnetic resonance vessel wall imaging.

Methods—
One hundred and five patients with ischemic stroke attributed to middle cerebral artery plaque underwent high-resolution black-blood magnetic resonance vessel wall imaging. They were divided into group 1, with the first episode of acute stroke (imaging within 4 weeks of stroke, n=44); group 2, with recurrent acute stroke (n=29); and group 3, with chronic stroke (imaging after 3 months of stroke, n=32). Plaque characteristics including plaque area, plaque burden, contrast-enhancement ratio, eccentricity, and degree of stenosis were measured and compared across 3 groups. Association between plaque characteristics and recurrent strokes was investigated by multivariate analysis.

Results—

Plaque burden was significantly greater in recurrent stroke group than the other 2 groups (median: group 2, 82.7%, versus group 1, 76.3%, and group 3, 73.4%;
P
=0.001). Patients with acute stroke had higher enhancement ratio than patients with chronic stroke (median: group 1, 1.59, and group 2, 1.90, versus group 3, 1.33;
P
=0.014). Comparing to first-onset acute stroke patients, recurrent stroke patients were older, more likely with female sex and hypertension, and had higher plaque burden. After adjustment of clinical factors, plaque burden was the only independent imaging feature associated with recurrent stroke (odds ratio, 2.26, per 10% increase [95% CI, 1.03–4.96];
P
=0.042).

Conclusions—
Higher plaque burden of middle cerebral artery identified on magnetic resonance vessel wall imaging is independently associated with recurrent ischemic stroke.
Biometric analysis of apical surgery-related anatomy of mandibular first molars: a cone-beam computed tomography study in a Mongoloid population
Authors: Wang Xue , Zhang Yuejiao , Li Xiaolan , Huang Zijing , Cui Minyi , Huang Zhuwei , Zhang Xiaolei , Hu Xiaoli 
Published: December 2019

Objective To evaluate the apical surgery-related anatomy of two-rooted and three-rooted mandibular first molars (MFMs) in a Mongoloid population. Methods A total of 502 cone-beam computed tomographic images were used to evaluate the root configuration, the distance from the buccal bone to each root, root dimensions, and the complete root resection distance at the resection level for roots of MFMs. Results The prevalence of two-rooted and three-rooted MFMs was 85.1% and 14.9%, respectively. At the resection level, the distance from the buccal bone to the mesial and distal roots of two-rooted MFMs was 2.24 and 3.15 mm, respectively, while the distance was 2.44, 2.01, and 8.55 mm for the mesial, distobuccal, and distolingual roots of three-rooted MFMs, respectively. The distance from the buccal bone to each root was longer in men than in women. The largest distance for complete root resection was detected for the distal root in two-rooted MFMs and for the distolingual root in three-rooted MFMs. Conclusions The prevalence of three-rooted MFMs is common in the Mongoloid population. The distance from the buccal bone to root apex differs according to root configurations and sex. Surgical access to the distolingual root is difficult because of the long access distance.
Fluorescently-labeled fremanezumab is distributed to sensory and autonomic ganglia and the dura but not to the brain of rats with uncompromised blood brain barrier
Authors: Noseda Rodrigo , Schain Aaron J , Melo-Carrillo Agustin , Tien Jason , Stratton Jennifer , Mai Fanny , Strassman Andrew M , Burstein Rami 
Published: December 2019

Background The presence of calcitonin gene-related peptide and its receptors in multiple brain areas and peripheral tissues previously implicated in migraine initiation and its many associated symptoms raises the possibility that humanized monoclonal anti-calcitonin gene-related peptide antibodies (CGRP-mAbs) can prevent migraine by modulating neuronal behavior inside and outside the brain. Critical to our ability to conduct a fair discussion over the mechanisms of action of CGRP-mAbs in migraine prevention is data generation that determines which of the many possible peripheral and central sites are accessible to these antibodies – a question raised frequently due to their large size. Material and methods Rats with uncompromised and compromised blood-brain barrier (BBB) were injected with Alexa Fluor 594-conjugated fremanezumab (Frema594), sacrificed 4 h or 7 d later, and relevant tissues were examined for the presence of Frema594. Results In rats with uncompromised BBB, Frema594 was similarly observed at 4 h and 7 d in the dura, dural blood vessels, trigeminal ganglion, C2 dorsal root ganglion, the parasympathetic sphenopalatine ganglion and the sympathetic superior cervical ganglion but not in the spinal trigeminal nucleus, thalamus, hypothalamus or cortex. In rats with compromised BBB, Frema594 was detected in the cortex (100 µm surrounding the compromised BBB site) 4 h but not 7 d after injections. Discussion Our inability to detect fluorescent (CGRP-mAbs) in the brain supports the conclusion that CGRP-mAbs prevent the headache phase of migraine by acting mostly, if not exclusively, outside the brain as the amount of CGRP-mAbs that enters the brain (if any) is too small to be physiologically meaningful.
Changing the Physical Activity Behavior of Adults With Fitness Trackers: A Systematic Review and Meta-Analysis
Authors: Lynch Chris , Bird Stephen , Lythgo Noel , Selva-Raj Isaac 
Published: December 2019

Objective:To examine whether a fitness tracker (FT) intervention changes physical activity (PA) behavior compared to a control condition or compared to an alternative intervention.Data Source:Searches between January 01, 2010, and January 01, 2019, were conducted in PubMed, CINAHL, Cochrane CENTRAL, EMBASE, and PsycINFO.Inclusion/Exclusion Criteria:Randomized clinical trials of adults using an FT to change PA behavior were included. Nonclinical trials, studies that included the delivery of structured exercise, and/or studies that only used the FT to assess PA were excluded.Data Extraction:Extracted features included characteristics of the study population, intervention components, PA outcomes, and results.Data Synthesis:Papers were pooled in a statistical meta-analysis using a fixed effects model. Where statistical pooling was not possible, standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated. Findings were presented in a narrative form and tables.Results:Of 2076 articles found, 21 were included in the review. A small yet significant positive effect (SMD = 0.25, 95% CI = 0.17-0.32; P < .01; I2= 56.9%; P = .03) was found in step count for interventions compared to control. A small yet significant negative effect (SMD = −0.11, 95% CI = −0.20 to −0.02; P = .02; I2= 58.2%; P = 0.03) was found in moderate-to-vigorous PA for interventions compared to an alternative intervention.Conclusion:Trackers may enhance PA interventions, as a general positive effect is found in step count compared to a control. However, there is no evidence of a positive effect when interventions are compared to an alternative intervention. It is unknown whether results are due to other intervention components and/or clinical heterogeneity.
Effectiveness of mobile phone-based self-management interventions for medication adherence and change in blood pressure in patients with coronary heart disease: A systematic review and meta-analysis
Authors: Sua Yun Shan , Jiang Ying , Thompson David R , Wang Wenru 
Published: December 2019

Aims: The aim of this study was to synthesise and evaluate the effectiveness of mobile phone-based self-management interventions for medication adherence and change in blood pressure in patients with coronary heart disease. Methods: Relevant randomised controlled trials evaluating mobile phone-based self-management interventions for medication adherence and/or change in blood pressure in coronary heart disease patients were identified by searching six electronic databases (PubMed, Cochrane, CINAHL, ProQuest, Scopus and EMBASE) from January 2008 to January 2019. The trials were screened, data were extracted and quality was assessed by two independent reviewers. Meta-analyses were performed for different outcomes while narrative syntheses were conducted for studies that could not be pooled or when there was the presence of high heterogeneity. Results: Fifteen trials were included in this review, of which 11 of these trials were meta-analysed. Mobile phone-based self-management interventions were associated with a statistically significant reduction in diastolic blood pressure (combined mean difference of −1.99 (95% confidence interval (CI) –3.20 to −0.78; P=0.0001)). However, the combined effect on medication adherence (medium size effect of d=0.72 (95% CI −0.32 to 1.75; P=0.17)) and change in systolic blood pressure (combined mean difference of −1.08 (95% CI −5.51 to 3.35; P=0.63)) was not statistically significant. There was significant heterogeneity among the trials reviewed. Conclusion: Mobile phone-based self-management interventions have the potential to improve self-management and adherence in patients with coronary heart disease but better designed, conducted and reported trials are needed to demonstrate this.
In Situ Treatment of Branch Renal Artery Aneurysms With Pantaloon Vein Graft
Authors: Irsara Sandro , Russo Francesco , Ferretto Luca 
Published: December 2019

Introduction: The optimal method of operative management of complex renal artery aneurysms (RAAs) involving distal branches (BRAAs) remains unclear. When more than 1 artery is involved within the BRAA, endovascular techniques are not advisable and an ex vivo approach is often preferred. In this study, we introduce an alternative surgical in situ technique to treat BRAAs. Methods and Surgical Technique: Five aneurysms involving the main or second-order bifurcation of the renal artery (RA) were treated in 4 patients at our institute between November 2012 and January 2017. The treatment of the BRAAs was based on resection of the aneurysm wall and reconstruction with autologous Pantaloon vein graft (PVG): a “Y-shaped” bypass created on-bench with autogenous great saphenous vein. Sequential clamping/reperfusion of the kidney allows to reduce renal function impairment. Results: No perioperative mortality or morbidity was observed, including none nephrectomy. In all the cases, aneurysms were treated with an in situ technique as previously planned. All the grafts were patent at the follow-up time (mean 64.1 ± 11.7 months). Renal function was preserved in all the cases. Vascularization of the renal parenchyma was satisfactory both on arterial echo Doppler and contrast-medium ultrasound in all the cases. Average cross-clamping times of the main RA and of a single branch RA were 15.8 ± 1.7 and 17.7 ± 4.6 minutes, respectively. Mean total operating time was 266.3 ± 18.9 minutes. Conclusion: The PVG with sequential clamping applied in the surgical treatment of BRAAs permits to reduce the ischemic effects to the renal parenchyma. To our knowledge, these are the first cases described in which BRAAs are treated with a PVG and our experience suggests that it is a feasible technique, with good long-term results and without severe adverse events recorded.
Systemic Pharmacokinetics of Topical Intranasal Cocaine in Healthy Subjects
Authors: McGrath John , McGrath Alexa , Burdett Jacob , Shokri Tom , Cohn Jason E. 
Published: December 2019

Background Topical cocaine is currently available for local anesthesia of the upper airway mucous membranes. Objective The objective of this study was to define the safety and efficacy of topical intranasal cocaine for a subsequent phase II clinical trial. Methods This study was a single-dose, single-center, and open-label study of the plasma and urinary pharmacokinetics (PK) of 4% topical cocaine and its major metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME), in 30 healthy subjects. Subjects received the topical solution on cotton pledgets containing 4 mL of 4% topical cocaine applied for 20 minutes, which was equivalent to 160 mg of cocaine hydrochloride. Results A total of 30 subjects (14 males and 16 females) were enrolled, treated, and provided PK data for analysis. Mean plasma concentrations of cocaine rose rapidly during the intranasal exposure period, with peak levels (Cmax, 37.0 ± 17.3 ng/mL) observed at the time of pledget removal (Tmax, 0.43 ± 0.34 h). Mean plasma concentrations then fell rapidly and monoexponentially for the remainder of the study, with a mean half-life (t1/2) of 1.04 ± 0.35 hours. Following a 20-minute topical intranasal exposure to a 160 mg dose of cocaine 4% solution, the mean 0 to 12 hours recoveries of cocaine, BE, and EME were 117 ± 67 μg, 816 ± 440 μg, and 275 ± 113 μg, respectively. Plotting urinary recovery by collection interval showed that urinary excretion of cocaine closely followed the time course of plasma cocaine. Conclusions Cocaine was rapidly but incompletely absorbed and then rapidly eliminated. Only 4% of the administered cocaine dose appeared to be absorbed in this study. Cocaine appeared in the urine with a time course similar to that in plasma.
The Influence of Surgical Timing on Clinical Outcomes in Primary Extramacular Retinal Detachment in a Tertiary Referral Center
Authors: Yannuzzi Nicolas A. , Brown Karen , Callaway Natalia F. , Patel Nimesh A. , Albini Thomas A. , Berrocal Audina M. , Davis Janet L. , Gregori Ninel N. , Fortun Jorge , Haddock Luis J. , Lee Wen-Hsiang , Schwartz Stephen G. , Sridhar Jayanth , Smiddy William E. , Flynn Harry W. , Townsend Justin 
Published: December 2019

Purpose: This article reports the influence of timing on the clinical outcomes in primary extramacular rhegmatogenous retinal detachment (RRD) at a tertiary referral center. Methods: A retrospective case series was conducted of all patients presenting between January 1, 2014 and December 31, 2016, with primary extramacular RRD. Retinal detachments with grade C proliferative vitreoretinopathy, combined tractional and RRD, eyes with inflammatory disease, and prior retinal surgery were excluded. The main outcome measures were single-operation anatomic success (SOAS), final anatomic success, and best-corrected visual acuity (BCVA). Results: There were 202 eyes of 198 patients with an average of 22 months’ follow-up (range, 6-47 months). Eyes were operated on an average of 1.1 days after initial presentation. At last clinical examination, SOAS had been achieved in 174 (86%) eyes, final anatomic success in 200 (99%) eyes, and average postoperative logarithm of the minimum angle of resolution (logMAR) BCVA was 0.18 (Snellen equivalent, 20/30; SD, 0.36). In those treated the day of presentation, average postoperative logMAR BCVA was 0.18 (Snellen, 20/31) in comparison to 0.18 (Snellen, 20/30) in those treated the day after presentation and 0.14 (Snellen, 20/28) in those treated after 2 days or more ( P = .92). Conclusions: Regarding timing of surgery, SOAS and BCVA outcomes in primary extramacular RRDs were favorable with an urgent and semiurgent approach to repair. There was no difference in visual and anatomic outcomes between patients who were operated on the day of presentation and those treated a short time later when clinical decisions were made by the treating surgeon on a case-by-case basis.