bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaborative Quality Improvement Reduces Postoperative Pneumonia After Isolated Coronary Artery Bypass Grafting Surgery
Authors: Likosky Donald S. , Harrington Steven D. , Cabrera Lourdes , DeLucia Alphonse , Chenoweth Carol E. , Krein Sarah L. , Thibault Dylan , Zhang Min , Matsouaka Roland A. , Strobel Raymond J. , Prager Richard L.
Published: January 2019

Background:

To date, studies evaluating outcome improvements associated with participation in physician-led collaboratives have been limited by the absence of a contemporaneous control group. We examined post cardiac surgery pneumonia rates associated with participation in a statewide, quality improvement collaborative relative to a national physician reporting program.

Methods and Results:

We evaluated 911 754 coronary artery bypass operations (July 1, 2011, to June 30, 2017) performed across 1198 hospitals participating in a voluntary national physician reporting program (Society of Thoracic Surgeons [STS]), including 33 that participated in a Michigan-based collaborative (MI-Collaborative). Unlike STS hospitals not participating in the MI-Collaborative (i.e., STSnonMI) that solely received blinded reports, MI-Collaborative hospitals received a multi-faceted intervention starting November 2012 (quarterly in-person meetings showcasing unblinded data, webinars, site visits). Eighteen of the MI-Collaborative hospitals received additional support to implement recommended pneumonia prevention practices (“MI-CollaborativePlus”), whereas 15 did not (“MI-CollaborativeOnly”). We evaluated rates of postoperative pneumonia, adjusting for patient mix and hospital effects. Baseline patient characteristics were qualitatively similar between groups and time. During the pre-intervention period (Q3/2011 through Q3/2012), there was no statistically significant difference in the adjusted odds of pneumonia for STS hospitals participating in the MI-Collaborative compared to the STS non-MI hospitals. However, during the intervention period (Q4/2012 through Q2/2017), there was a significant 2% reduction per quarter in the adjusted odds of pneumonia for MI-Collaborative hospitals (
n
=33) relative to the STS non-MI hospitals. There was a significant 3% per quarter reduction in the adjusted odds of pneumonia for the MI-Collaborative Only (
n
=15) hospitals relative to the STS non-MI hospitals. Over the course of the overall study period, the STS non-MI hospitals had a 1.96% reduction in risk-adjusted pneumonia (pre- vs. intervention periods), which was less than the MI-Collaborative (3.23%,
P
=0.011). Over the same time period, the MI-Collaborative Plus (
n
=18) reduced adjusted pneumonia rates by 10.29%,
P
=0.001.

Conclusions:

Participation in a physician-led collaborative was associated with significant reductions in pneumonia relative to a national quality reporting program. Interventions including collaborative learning may yield superior outcomes relative to solely using physician feedback reporting.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02068716.
Hospital Variation in the Utilization and Implementation of Targeted Temperature Management in Out-of-Hospital Cardiac Arrest
Authors: Khera Rohan , Humbert Andrew , Leroux Brian , Nichol Graham , Kudenchuk Peter , Scales Damon , Baker Andrew , Austin Mike , Newgard Craig D. , Radecki Ryan , Vilke Gary M. , Sawyer Kelly N. , Sopko George , Idris Ahamed H. , Wang Henry , Chan Paul S. , Kurz Michael C. ,   for the Resuscitation Outcomes Consortium Investigators
Published: January 2019

Background

Targeted temperature management (TTM) for out-of-hospital cardiac arrest is associated with improved functional survival and is a class I recommendation in resuscitation guidelines. However, patterns of utilization of TTM and adherence to recommended TTM guidelines in contemporary practice are unknown.

Methods and Results

In a multicenter, prospective cohort of consecutive adults with non-traumatic out-of-hospital cardiac arrest in the Resuscitation Outcomes Consortium in 2012 to 2015, we identified all adults (≥18 years) who were potential candidates for TTM. Of 37 898 out-of-hospital cardiac arrest patients at 186 hospitals across 10 Resuscitation Outcomes Consortium sites, 8313 survived for ≥4 hours after hospital arrival, of which, 2878 (34.6%) received TTM. Mean age was 61.5 years and 36.3% were women. Median hospital rate of TTM use was 27% (interquartile range [IQR]: 14%, 45%), with an over 2-fold difference across sites after accounting for differences in presentation characteristics (median odds ratio, 2.10 [1.83–2.26]). Notably, TTM utilization decreased during the study period (57.5% [2012] to 26.5% [2015],
P
<0.001) including among shockable out-of-hospital cardiac arrest (73.4% to 46.3%,
P
<0.001). When administered, the median rate of deviation from one or more recommended practices was 60% (IQR: 40%, 78%). The median rate for delayed onset of TTM was 13% (IQR: 0%, 25%), varying by 70% for identical patients across 2 randomly chosen hospitals (median odds ratio 1.70 [1.39–1.97]). Similarly, the median rate for TTM <24 hours was 20% (IQR: 0%, 34%) and for achieved temperature <32°C was 18% (IQR: 0%, 39%), with marked variation across sites (median odds ratios of 1.44 [1.18–1.64] and 1.98 [1.62–2.31], respectively).

Conclusions

There has been a substantial decline in the utilization of TTM with significant variation in its real-world implementation. Further standardization of contemporary post-resuscitation practices, like TTM, is critical to ensure that their potential survival benefit is realized.
A Phase 2 Randomized, Sham-Controlled Trial of Internal Carotid Artery Infusion of Autologous Bone Marrow–Derived ALD-401 Cells in Patients With Recent Stable Ischemic Stroke (RECOVER-Stroke)
Authors: Savitz Sean I. , Yavagal Dileep , Rappard George , Likosky William , Rutledge Neal , Graffagnino Carmelo , Alderazi Yazan , Elder Jennifer A. , Chen Peng R. , Budzik Ronald F. , Tarrel Ronald , Huang David Y. , Hinson James M. ,   On behalf of the ALD-401 Trial Group
Published: January 2019

Background:

Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow–derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy.

Methods:

This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications.

Results:

There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, –0.3 to 0.8;
P
=0.330). There were no significant differences between the groups on any of the secondary efficacy measures.

Conclusions:

Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01273337.
Bacteroides vulgatus
and
Bacteroides dorei
Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis
Authors: Yoshida Naofumi , Emoto Takuo , Yamashita Tomoya , Watanabe Hikaru , Hayashi Tomohiro , Tabata Tokiko , Hoshi Namiko , Hatano Naoya , Ozawa Genki , Sasaki Naoto , Mizoguchi Taiji , Amin Hilman Zulkifli , Hirota Yushi , Ogawa Wataru , Yamada Takuji , Hirata Ken-ichi
Published: January 2019

Background:

It is increasingly recognized that gut microbiota play a pivotal role in the development of atherosclerotic cardiovascular disease. Previously, we have reported that the abundance of genus
Bacteroides
is lower in patients with coronary artery disease (CAD) than in patients without CAD with coronary risk factors or in healthy volunteers. However, it remains unclear which and how specific gut bacteria contribute to the progression of atherosclerosis.

Methods:

We recruited patients with CAD patients and controls without CAD with coronary risk factors. We then compared gut microbial composition using 16S ribosomal RNA gene sequencing in fecal samples to detect species with differential abundance between 2 groups. Subsequently, we used atherosclerosis-prone mice to study the mechanisms underlying the relationship between such species and atherosclerosis.

Results:

Human fecal 16S ribosomal RNA gene sequencing revealed a significantly lower abundance of
Bacteroides vulgatus
and
Bacteroides dorei
in patients with CAD. This significant differential abundance was confirmed by quantitative polymerase chain reaction. Gavage with live
B. vulgatus
and
B. dorei
attenuated atherosclerotic lesion formation in atherosclerosis-prone mice, markedly ameliorating endotoxemia followed by decreasing gut microbial lipopolysaccharide production, effectively suppressing proinflammatory immune responses. Furthermore, fecal lipopolysaccharide levels in patients with CAD were significantly higher and negatively correlated with the abundance of
B. vulgatus
and
B. dorei
.

Conclusions:

Our translational research findings identify a previously unknown link between specific gut bacteria and atherosclerosis. Treatment with live
B. vulgatus
and
B. dorei
may help prevent CAD.

Clinical Trial Registration:

URL:
https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018051
. Unique identifier: UMIN000015703.
Bcl2-Like Protein 12 Is Required for the Aberrant T Helper-2 Polarization in the Heart by Enhancing Interleukin-4 Expression and Compromising Apoptotic Machinery in CD4+ T Cells
Authors: Chen Xiao , Zeng Xian-Hai , Wang Mangyuan , Chen Liang , Zhang Ningning , Rao Man , Yang Ping-Chang , Song Jiangping
Published: January 2019

Background:

The biased T helper-2 (Th2) response plays a critical role in myocarditis. Bcl2-like protein 12 (Bcl2L12) is associated with the Th2 pattern of inflammation. This study aims to elucidate the role of Bcl2L12 in the pathogenesis of Th2-biased inflammation in the heart.

Methods:

Mice were treated with the myosin heavy-chain-α peptides to induce inflammation in the heart. Human hearts were collected from the surgically removed hearts of patients who had undergone heart transplantation.

Results:

The expression of Bcl2L12 was detected in CD4
+
T cells of the hearts, which was markedly higher in the hearts with myocarditis at the advanced stage of heart failure compared with the control (dilated cardiomyopathy) hearts without myocarditis. Mice with Bcl2L12-deficient CD4
+
T cells failed to induce the Th2-biased inflammation in the heart. CD4
+
T cells with a higher expression of Bcl2L12 were prone to differentiate into Th2 cells. Bcl2L12 formed a complex with GATA3 in CD4
+
T cells to enhance the binding between GATA3 and the
Il4
promoter, which promoted the
Il4
gene transcription. Bcl2L12 compromised the apoptotic machinery by inhibiting the expression of p53 in CD4
+
T cells to reduce the activation-induced CD4
+
T cell death.

Conclusions:

CD4
+
T cells isolated from hearts with myocarditis at the end stage of heart failure express high levels of Bcl2L12, and the latter is required for the development of aberrant Th2 polarization in the heart. The Bcl2L12 may be a novel target in the treatment of myocarditis as well as other Th2-biased inflammation.
Long-Term Association of Low-Density Lipoprotein Cholesterol With Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease
Authors: Abdullah Shuaib M. , Defina Laura F. , Leonard David , Barlow Carolyn E. , Radford Nina B. , Willis Benjamin L. , Rohatgi Anand , McGuire Darren K. , de Lemos James A. , Grundy Scott M. , Berry Jarett D. , Khera Amit
Published: January 2019

Background:

The associations of low-density lipoprotein cholesterol (LDL-C) with cardiovascular disease (CVD) and coronary heart disease mortality in an exclusively low estimated 10-year risk group are not well delineated. We sought to determine the long-term associations of various LDL-C and non–high-density lipoprotein cholesterol (HDL-C) thresholds and CVD and coronary heart disease mortality in a large, low 10-year risk cohort.

Methods:

The study sample included participants of the CCLS (Cooper Center Longitudinal Study) without a history of CVD or diabetes mellitus and defined as low risk (<7.5%) for 10-year atherosclerotic CVD events at baseline based on Pooled Cohort Risk Assessment Equations. The associations of fasting LDL-C and non–HDL-C with CVD mortality were tested with Cox proportional hazards models.

Results:

In 36 375 participants (72% men, median age 42) followed for a median of 26.8 years, 1086 CVD and 598 coronary heart disease deaths occurred. Compared with LDL-C <100 mg/dL, LDL-C categories 100 to 129 mg/dL, 130 to 159 mg/dL, 160 to 189.9 mg/dL, and ≥190 mg/dL were associated with a significantly higher risk of CVD death, with hazard ratios of 1.4 (95% CI, 1.1–1.7), 1.3 (95% CI, 1.1–1.6), 1.9 (95% CI, 1.5–2.4), and 1.7 (95% CI, 1.3–2.3), and mean reductions in years free of CVD death of 1.8, 1.1, 4.3, and 3.9, respectively. After adjustment for atherosclerotic CVD risk factors, LDL-C categories 160 to 189 mg/dL and ≥190 mg/dL remained independently associated with CVD mortality, with hazard ratios of 1.7 (95% CI, 1.4–2.2) and 1.5 (95% CI, 1.2–2.1), respectively. In multivariable-adjusted models using non–HDL-C <130 mg/dL as the reference, non–HDL-C 160 to 189 mg/dL, 190 to 219 mg/dL, and ≥220 mg/dL were significantly associated with CVD death, with hazard ratios of 1.3 (95% CI, 1.1–1.6), 1.8 (95% CI, 1.4–2.2), and 1.5 (95% CI, 1.2–2.0), respectively. Restricting the cohort to those with 10-year risk <5% did not diminish the associations of LDL-C and non–HDL-C with CVD mortality.

Conclusions:

In a low 10-year risk cohort with long-term follow-up, LDL-C and non–HDL-C ≥160 mg/dL were independently associated with a 50% to 80% increased relative risk of CVD mortality. These findings may have implications for future cholesterol treatment paradigms.
Oxidized Low-Density Lipoprotein Receptor in Lymphocytes Prevents Atherosclerosis and Predicts Subclinical Disease
Authors: Tsilingiri Katerina , de la Fuente Hortensia , Relaño Marta , Sánchez-Díaz Raquel , Rodríguez Cristina , Crespo Javier , Sánchez-Cabo Fátima , Dopazo Ana , Alonso-Lebrero José L. , Vara Alicia , Vázquez Jesús , Casasnovas José M. , Alfonso Fernando , Ibáñez Borja , Fuster Valentín , Martínez-González José , Martín Pilar , Sánchez-Madrid Francisco
Published: January 2019

Background:

Although the role of Th17 and regulatory T cells in the progression of atherosclerosis has been highlighted in recent years, their molecular mediators remain elusive. We aimed to evaluate the association between the CD69 receptor, a regulator of Th17/regulatory T cell immunity, and atherosclerosis development in animal models and in patients with subclinical disease.

Methods:

Low-density lipoprotein receptor–deficient chimeric mice expressing or not expressing CD69 on either myeloid or lymphoid cells were subjected to a high fat diet. In vitro functional assays with human T cells were performed to decipher the mechanism of the observed phenotypes. Expression of CD69 and NR4A nuclear receptors was evaluated by reverse transcription–polymerase chain reaction in 305 male participants of the PESA study (Progression of Early Subclinical Atherosclerosis) with extensive (n=128) or focal (n=55) subclinical atherosclerosis and without disease (n=122).

Results:

After a high fat diet, mice lacking CD69 on lymphoid cells developed large atheroma plaque along with an increased Th17/regulatory T cell ratio in blood. Oxidized low-density lipoprotein was shown to bind specifically and functionally to CD69 on human T lymphocytes, inhibiting the development of Th17 cells through the activation of NR4A nuclear receptors. Participants of the PESA study with evidence of subclinical atherosclerosis displayed a significant CD69 and NR4A1 mRNA downregulation in peripheral blood leukocytes compared with participants without disease. The expression of CD69 remained associated with the risk of subclinical atherosclerosis in an adjusted multivariable logistic regression model (odds ratio, 0.62; 95% CI, 0.40–0.94;
P
=0.006) after adjustment for traditional risk factors, the expression of NR4A1, the level of oxidized low-density lipoprotein, and the counts of different leucocyte subsets.

Conclusions:

CD69 depletion from the lymphoid compartment promotes a Th17/regulatory T cell imbalance and exacerbates the development of atherosclerosis. CD69 binding to oxidized low-density lipoprotein on T cells induces the expression of anti-inflammatory transcription factors. Data from a cohort of the PESA study with subclinical atherosclerosis indicate that CD69 expression in PBLs inversely correlates with the presence of disease. The expression of CD69 remained an independent predictor of subclinical atherosclerosis after adjustment for traditional risk factors.
Genetically Determined Levels of Circulating Cytokines and Risk of Stroke
Authors: Georgakis Marios K. , Gill Dipender , Rannikmäe Kristiina , Traylor Matthew , Anderson Christopher D. ,   MEGASTROKE consortium of the International Stroke Genetics Consortium (ISGC), Lee Jin-Moo , Kamatani Yoichiro , Hopewell Jemma C. , Worrall Bradford B. , Bernhagen Jürgen , Sudlow Cathie L. M. , Malik Rainer , Dichgans Martin
Published: January 2019

Background:

Cytokines and growth factors have been implicated in the initiation and propagation of vascular disease. Observational studies have shown associations of their circulating levels with stroke. Our objective was to explore whether genetically determined circulating levels of cytokines and growth factors are associated with stroke and its etiologic subtypes by conducting a 2-sample Mendelian randomization (MR) study.

Methods:

Genetic instruments for 41 cytokines and growth factors were obtained from a genome-wide association study of 8293 healthy adults. Their associations with stroke and stroke subtypes were evaluated in the MEGASTROKE genome-wide association study data set (67 162 cases; 454 450 controls) applying inverse variance–weighted meta-analysis, weighted-median analysis, Mendelian randomization–Egger regression, and multivariable Mendelian randomization. The UK Biobank cohort was used as an independent validation sample (4985 cases; 364 434 controls). Genetic instruments for monocyte chemoattractant protein-1 (MCP-1/CCL2) were further tested for association with etiologically related vascular traits by using publicly available genome-wide association study data.

Results:

Genetic predisposition to higher MCP-1 levels was associated with higher risk of any stroke (odds ratio [OR] per 1 SD increase, 1.06; 95% CI, 1.02–1.09;
P
=0.0009), any ischemic stroke (OR, 1.06; 95% CI, 1.02–1.10;
P
=0.002), large-artery stroke (OR, 1.19; 95% CI, 1.09–1.30;
P
=0.0002), and cardioembolic stroke (OR, 1.14; 95% CI, 1.06–1.23;
P
=0.0004), but not with small-vessel stroke or intracerebral hemorrhage. The results were stable in sensitivity analyses and remained significant after adjustment for cardiovascular risk factors. Analyses in the UK Biobank showed similar associations for available phenotypes (any stroke: OR, 1.08; 95% CI, 0.99–1.17;
P
=0.09; any ischemic stroke: OR, 1.07; 95% CI, 0.97–1.18;
P
=0.17). Genetically determined higher MCP-1 levels were further associated with coronary artery disease (OR, 1.04; 95% CI, 1.00–1.08;
P
=0.04) and myocardial infarction (OR, 1.05; 95% CI, 1.01–1.09;
P
=0.02), but not with atrial fibrillation. A meta-analysis of observational studies showed higher circulating MCP-1 levels in patients with stroke in comparison with controls.

Conclusions:

Genetic predisposition to elevated circulating levels of MCP-1 is associated with higher risk of stroke, in particular with large-artery stroke and cardioembolic stroke. Whether targeting MCP-1 or its receptors can lower stroke incidence requires further study.
Endovascular Fenestration/Stenting First Followed by Delayed Open Aortic Repair for Acute Type A Aortic Dissection With Malperfusion Syndrome
Authors: Yang Bo , Rosati Carlo Maria , Norton Elizabeth L. , Kim Karen M. , Khaja Minhaj S. , Dasika Narasimham , Wu Xiaoting , Hornsby Whitney E. , Patel Himanshu J. , Deeb G. Michael , Williams David M.
Published: January 2019

Background:

Immediate open repair of acute type A aortic dissection is traditionally recommended to prevent death from aortic rupture. However, organ failure because of malperfusion syndrome (MPS) might be the most imminent life-threatening problem for a subset of patients.

Methods:

From 1996 to 2017, among 597 patients with acute type A aortic dissection, 135 patients with MPS were treated with upfront endovascular reperfusion (fenestration/stenting) followed by delayed open repair (OR). We compared outcomes between the first and second decades and observed mortalities with those expected with an “upfront OR for every patient” approach, determined using prognostic models from the literature (Verona, Leipzig-Halifax, Stockholm, Penn, and GERAADA [German Registry for Acute Aortic Dissection Type A] models).

Results:

Overall, in-hospital mortality improved between the 2 decades (21.0% versus 10.7%,
P
<0.001). In the second decade, for patients with MPS initially treated with fenestration/stenting, mortality from aortic rupture decreased from 16% to 4% (
P
=0.05), the risk of dying from organ failure was 6.6 times higher than dying from aortic rupture (hazard ratio=6.63; 95% CI, 1.5–29;
P
=0.01), and 30-day mortality after OR for MPS patients was 3.7%. Compared to the expected mortalities with the upfront OR for every patient models, our observed 30-day and in-hospital mortalities (9% and 11%, respectively) of all patients with acute type A aortic dissection were significantly lower (
P
≤0.03).

Conclusions:

Immediate OR is the strategy to prevent death from aortic rupture for the majority of patients with acute type A aortic dissection. However, relatively stable (no rupture, no tamponade) patients with MPS benefit from a staged approach: upfront endovascular reperfusion followed by aortic OR at resolution of organ failure.
Components and Trends in Door to Treatment Times for Endovascular Therapy in Get With The Guidelines-Stroke Hospitals
Authors: Menon Bijoy K. , Xu Haolin , Cox Margueritte , Saver Jeffrey L. , Goyal Mayank , Peterson Eric , Xian Ying , Matsuoka Roland , Jehan Reza , Yavagal Dileep , Gupta Rishi , Mehta Brijesh , Bhatt Deepak L. , Fonarow Gregg C. , Schwamm Lee H. , Smith Eric E.
Published: January 2019

Background:

Endovascular therapy (EVT) is standard of care in patients with acute disabling ischemic stroke attributable to large-vessel occlusion and is more effective when delivered quickly. It is currently unclear whether time targets achieved in clinical trials can be achieved in clinical practice. We describe interval times from patient arrival in the emergency department (door) to first pass (treatment initiation) in patients receiving EVT within Get With The Guidelines-Stroke hospitals and analyze patient- and hospital-level variables associated with these times.

Methods:

Data are from sites participating fully as Comprehensive Stroke Centers within Get With The Guidelines-Stroke hospitals from October 2014 to September 2016. Workflow times analyzed include door to imaging, imaging to arterial access, arterial access to first pass, and the composite door to first pass time. Data are described overall and by calendar-year quarters. Multivariable modeling was used to identify patient- and hospital-level variables associated with workflow times.

Results:

Among 2929 patients with EVT from 195 hospitals (median age, 71 years [interquartile range {IQR}, 60–81]; 50.7% female; median baseline National Institute of Health Stroke Score, 17 [IQR, 12–22]; median annual EVT administration number, 16 [IQR, 10–27]), median door to first pass time was 130 minutes (IQR, 101–170 minutes), door to imaging time was 12 minutes (IQR, 7–20 minutes), imaging to arterial puncture time was 93 minutes (IQR, 68–126 minutes), and arterial puncture to first pass time was 18 minutes (IQR, 4–31 minutes). Overall, 3% patients achieved a door to first pass time ≤60 minutes. A statistically significant linear time trend was noted for door to first pass time (quarter 4 year 2014 median time, 134.5 minutes to quarter 3 year 2016 median time, 128 minutes,
P
=0.002). In multivariable analysis, older age, arrival during nonregular hours, and history of diabetes mellitus were associated with longer door to first pass time. Hospitals achieving shorter door to intravenous alteplase administration (door to needle) times were more likely to achieve faster door to first pass time (
P
<0.001). Each 5 cases/y increase in EVT case volume was associated with a 3% shorter door to first pass time, up to a case volume of 40 per year (
P
<0.001).

Conclusions:

Although EVT treatment times are modestly improving, additional efforts are needed to streamline workflow so that the true potential of this treatment is realized. These data may inform benchmark goals for EVT workflow times.
High-Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice
Authors: Peri-Okonny Poghni , Baskin Kedryn K. , Iwamoto Gary , Mitchell Jere H. , Smith Scott A. , Kim Han Kyul , Szweda Luke I. , Bassel-Duby Rhonda , Fujikawa Teppei , Castorena Carlos M. , Richardson James , Shelton John M. , Ayers Colby , Berry Jarett D. , Malladi Venkat S. , Hu Ming-Chang , Moe Orson W. , Scherer Philipp E. , Vongpatanasin Wanpen
Published: January 2019

Background:

Inorganic phosphate (Pi) is used extensively as a preservative and a flavor enhancer in the Western diet. Physical inactivity, a common feature of Western societies, is associated with increased cardiovascular morbidity and mortality. It is unknown whether dietary Pi excess contributes to exercise intolerance and physical inactivity.

Methods:

To determine an association between Pi excess and physical activity in humans, we assessed the relationship between serum Pi and actigraphy-determined physical activity level, as well as left ventricular function by cardiac magnetic resonance imaging, in DHS-2 (Dallas Heart Study phase 2) participants after adjusting for relevant variables. To determine direct effects of dietary Pi on exercise capacity, oxygen uptake, serum nonesterified fatty acid, and glucose were measured during exercise treadmill test in C57/BL6 mice fed either a high-Pi (2%) or normal-Pi (0.6%) diet for 12 weeks. To determine the direct effect of Pi on muscle metabolism and expression of genes involved in fatty acid metabolism, additional studies in differentiated C2C12 myotubes were conducted after subjecting to media containing 1 to 3 mmol/L Pi (pH 7.0) to simulate in vivo phosphate conditions.

Results:

In participants of the DHS-2 (n=1603), higher serum Pi was independently associated with reduced time spent in moderate to vigorous physical activity (
P
=0.01) and increased sedentary time (
P
=0.004). There was no association between serum Pi and left ventricular ejection fraction or volumes. In animal studies, compared with the control diet, consumption of high-Pi diet for 12 weeks did not alter body weight or left ventricular function but reduced maximal oxygen uptake, treadmill duration, spontaneous locomotor activity, fat oxidation, and fatty acid levels and led to downregulation of genes involved in fatty acid synthesis, release, and oxidation, including
Fabp4
,
Hsl
,
Fasn
, and
Pparγ
, in muscle. Similar results were recapitulated in vitro by incubating C2C12 myotubes with high-Pi media.

Conclusions:

Our data demonstrate a detrimental effect of dietary Pi excess on skeletal muscle fatty acid metabolism and exercise capacity that is independent of obesity and cardiac contractile function. Dietary Pi may represent a novel and modifiable target to reduce physical inactivity associated with the Western diet.
Poor Oral Health and Blood Pressure Control Among US Hypertensive Adults
Authors: Pietropaoli Davide , Del Pinto Rita , Ferri Claudio , Wright Jackson T. , Giannoni Mario , Ortu Eleonora , Monaco Annalisa
Published: January 2019

Periodontal disease is a chronic inflammatory disorder of the tissues surrounding the teeth, with evidence of systemic effects. Some studies showed the benefit of periodontal therapy on blood pressure (BP), but the impact of periodontitis on BP control is unknown. We retrospectively analyzed cross-sectional, nationally representative data from treated hypertensive adults aged ≥30 years with and without periodontitis. BP was examined as both continuous (mm Hg) and categorical (treatment goal achievement status according to guidelines: at goal and above goal) variable according to the presence or absence of periodontitis and its clinical parameters (probing depth, clinical attachment loss, and disease severity [mild, moderate, and severe]). Systolic BP means and odds ratios for uncontrolled BP according to the presence and severity of periodontitis were calculated using progressively adjusted models. Among treated hypertensive adults, mean systolic BP was about 2.3 to 3 mm Hg higher in the presence of periodontitis (
P
<0.0001). Periodontitis was associated with unsuccessful antihypertensive treatment after multiple adjustments, with higher odds by disease severity. A good periodontal health is associated with better systolic BP profile during antihypertensive therapy by about 2.3 to 3 mm Hg and with lower odds of antihypertensive treatment failure. Dedicated studies are needed to test the impact of periodontal therapy on BP and the long-term effects on cardiovascular outcomes of this complementary approach to systemic health.
Testing Computer Models Predicting Human Responses to a High-Salt Diet
Authors: Kurtz Theodore W. , DiCarlo Stephen E. , Pravenec Michal , Ježek Filip , Šilar Jan , Kofránek Jiří , Morris R. Curtis
Published: January 2019

Recently, mathematical models of human integrative physiology, derived from Guyton’s classic 1972 model of the circulation, have been used to investigate potential mechanistic abnormalities mediating salt sensitivity and salt-induced hypertension. We performed validation testing of 2 of the most evolved derivatives of Guyton’s 1972 model, Quantitative Cardiovascular Physiology-2005 and HumMod-3.0.4, to determine whether the models accurately predict sodium balance and hemodynamic responses of normal subjects to increases in salt intake within the real-life range of salt intake in humans. Neither model, nor the 1972 Guyton model, accurately predicts the usual changes in sodium balance, cardiac output, and systemic vascular resistance that normally occur in response to clinically realistic increases in salt intake. Furthermore, although both contemporary models are extensions of the 1972 Guyton model, testing revealed major inconsistencies between model predictions with respect to sodium balance and hemodynamic responses of normal subjects to short-term and long-term salt loading. These results demonstrate significant limitations with the hypotheses inherent in the Guyton models regarding the usual regulation of sodium balance, cardiac output, and vascular resistance in response to increased salt intake in normal salt-resistant humans. Accurate understanding of the normal responses to salt loading is a prerequisite for accurately establishing abnormal responses to salt loading. Accordingly, the present results raise concerns about the interpretation of studies of salt sensitivity with the various Guyton models. These findings indicate a need for continuing development of alternative models that incorporate mechanistic concepts of blood pressure regulation fundamentally different from those in the 1972 Guyton model and its contemporary derivatives.
Different Effects of Vascular Aging on Ischemic Predisposition in Healthy Men and Women
Authors: Namasivayam Mayooran , McEniery Carmel M. , Wilkinson Ian B. , Yasmin  , Cockroft John R. , McDonnell Barry J. , Adji Audrey , O’Rourke Michael F. ,   on behalf of the Anglo-Cardiff Collaborative Trial Investigators
Published: January 2019

Invasive studies of the twentieth century showed the value of aortic pressure-time integrals as markers of myocardial oxygen demand and supply. More recent studies have used these concepts to evaluate the mechanisms of ischemic predisposition using noninvasive arterial tonometry in cardiology outpatients. We sought to evaluate the spectrum of myocardial oxygen demand and supply in a large cross-sectional community sample of healthy volunteers and identify the roles of age, sex, and wave reflection. Arterial tonometry was performed in 3682 healthy volunteers. Measures of systolic and diastolic pressure-time integrals and their ratio in addition to cardiac ejection duration were determined and analyzed by age and sex. Multiple regression analyses were performed to identify the mechanisms underlying observations, while controlling for confounders (heart rate, height, weight, and mean pressure). In a healthy cohort, older women more than men (
P
<0.001) had unfavorable myocardial oxygen supply:demand ratios because of differing effects of vascular aging.
CT-1 (Cardiotrophin-1)-Gal-3 (Galectin-3) Axis in Cardiac Fibrosis and Inflammation
Authors: Martínez-Martínez Ernesto , Brugnolaro Cristina , Ibarrola Jaime , Ravassa Susana , Buonafine Mathieu , López Begoña , Fernández-Celis Amaya , Querejeta Ramón , Santamaria Enrique , Fernández-Irigoyen Joaquín , Rábago Gregorio , Moreno María U , Jaisser Frédéric , Díez Javier , González Arantxa , López-Andrés Natalia
Published: January 2019

Myocardial fibrosis is a main contributor to the development of heart failure (HF). CT-1 (cardiotrophin-1) and Gal-3 (galectin-3) are increased in HF and associated with myocardial fibrosis. The aim of this study is to analyze whether CT-1 regulates Gal-3. Proteomic analysis revealed that Gal-3 was upregulated by CT-1 in human cardiac fibroblasts in parallel with other profibrotic and proinflammatory markers. CT-1 upregulation of Gal-3 was mediated by ERK (extracellular signal-regulated kinase) 1/2 and Stat-3 (signal transducer and activator of transcription 3) pathways. Male Wistar rats and B6CBAF1 mice treated with CT-1 (20 µg/kg per day) presented higher cardiac Gal-3 levels and myocardial fibrosis. In CT-1–treated rats, direct correlations were found between cardiac CT-1 and Gal-3 levels, as well as between Gal-3 and perivascular fibrosis. Gal-3 genetic disruption in human cardiac fibroblasts and pharmacological Gal-3 inhibition in mice prevented the profibrotic and proinflammatory effects of CT-1. Dahl salt-sensitive hypertensive rats with diastolic dysfunction showed increased cardiac CT-1 and Gal-3 expression together with cardiac fibrosis and inflammation. CT-1 and Gal-3 directly correlated with myocardial fibrosis. In HF patients, myocardial and plasma CT-1 and Gal-3 were increased and directly correlated. In addition, HF patients with high CT-1 and Gal-3 plasma levels presented an increased risk of cardiovascular death. Our data suggest that CT-1 upregulates Gal-3 which, in turn, mediates the proinflammatory and profibrotic myocardial effects of CT-1. The elevation of both molecules in HF patients identifies a subgroup of patients with a higher risk of cardiovascular mortality. The CT-1/Gal-3 axis emerges as a candidate therapeutic target and a potential prognostic biomarker in HF.
Superimposed Preeclampsia Exacerbates Postpartum Renal Injury Despite Lack of Long-Term Blood Pressure Difference in the Dahl Salt-Sensitive Rat
Authors: Turbeville Hannah R. , Taylor Erin B. , Garrett Michael R. , Didion Sean P. , Ryan Michael J. , Sasser Jennifer M.
Published: January 2019

Preeclampsia results in increased susceptibility to hypertension and chronic kidney disease postpartum; however, the mechanisms responsible for disease progression in these women remain unknown. The purpose of this study was to test the hypothesis that 2 mechanisms contribute to the link between the maternal syndrome of preeclampsia and the increased postpartum risk of cardiovascular and renal disease: (1) increased T cells in the kidney and (2) a decreased NO:ET-1 (endothelin-1) ratio. Dahl S rats (a previously characterized model of preeclampsia superimposed on chronic hypertension) who experienced 2 pregnancies and virgin littermate controls were studied at 6 months of age. Mean arterial pressure was measured via telemetry, and renal injury was assessed through both histological analysis and measurement of urinary markers including nephrin, podocalyxin, and KIM-1 (kidney injury marker 1). Contributing mechanisms were assessed through flow cytometric analysis of renal T cells, quantification of plasma TNF-α (tumor necrosis factor-α) and IL-10 (interleukin-10), and quantification of urinary concentrations of NO metabolites and ET-1. Although prior pregnancy did not exacerbate the hypertension at 6 months, this group showed greater renal injury compared with virgin littermates. Flow cytometric analyses revealed an increase in renal T cells after pregnancy, and cytokine analysis revealed a systemic proinflammatory shift. Finally, the NO:ET-1 ratio was reduced. These results demonstrate that the link between the maternal syndrome of superimposed preeclampsia and postpartum risk of chronic kidney disease could involve both immune system activation and dysregulation of the NO:ET-1 balance.
High Normal Blood Pressure and Left Ventricular Hypertrophy Echocardiographic Findings From the PAMELA Population
Authors: Cuspidi Cesare , Facchetti Rita , Bombelli Michele , Tadic Marijana , Sala Carla , Grassi Guido , Mancia Giuseppe
Published: January 2019

Cross-sectional and longitudinal data analysis of the PAMELA (Pressioni Monitorate E Loro Associazioni) population was performed to assess the association between prehypertension and left ventricular hypertrophy (LVH) at entry and the risk of new-onset LVH associated to this condition in the subset of participants with normal LV mass index (LVMI). A total of untreated 1397 participants with measurable echocardiographic parameters at baseline were considered in the cross-sectional analysis. The longitudinal analysis included 880 participants without LVH at baseline and with measurable LVMI at follow-up examination performed 10 years later. At entry, after adjustment for major confounders LVH prevalence rates (LVM/body surface area) showed a significant, progressive increase from the normotensive (2.1%), to prehypertension (6.7%), and hypertension group (18.3%). The incidence of LVH increased progressively from the normotensive to prehypertension and hypertension group (9.0%, 23.2%, and 36.5%, respectively). The risk of new LVH was significantly greater in prehypertension who progressed to sustained hypertension (odds ratio, 4.21; CI, 1.64–10.83;
P
=0.003) than in those with persistent prehypertension (odds ratio, 1.89; CI, 0.77–5.11;
P
=0.21) compared with persistent normotensive participants after adjustment for age, sex, baseline LVMI, obesity, glucose, creatinine, total cholesterol and the use of antihypertensive drugs at follow-up. Further adjustments for changes in body mass index, metabolic variables, and creatinine during the follow-up did not modify the strength of association between prehypertension and new-onset LVH. Our findings offer a new piece of evidence on the association of prehypertension with LVH and support the view that preventive actions for this condition affecting a large fraction of the general population should be intensified.
Community‐Wide Dissemination of Bystander Cardiopulmonary Resuscitation and Automated External Defibrillator Use Using a 45‐Minute Chest Compression–Only Cardiopulmonary Resuscitation Training
Authors: Nishiyama Chika , Kitamura Tetsuhisa , Sakai Tomohiko , Murakami Yukiko , Shimamoto Tomonari , Kawamura Takashi , Yonezawa Takahiro , Nakai Shohei , Marukawa Seishiro , Sakamoto Tetsuya , Iwami Taku
Published: January 2019

Background

Little is known about whether cardiopulmonary resuscitation (
CPR
) training can increase bystander
CPR
in the community or the appropriate target number of
CPR
trainings. Herein, we aimed to demonstrate community‐wide aggressive dissemination of
CPR
training and evaluate temporal trends in bystander
CPR
.

Methods and Results

We provided
CPR
training (45‐minute chest compression–only
CPR
plus automated external defibrillator use training or the conventional
CPR
training), targeting 16% of residents. All emergency medical service–treated out‐of‐hospital cardiac arrests of medical origin were included. Data on patients experiencing out‐of‐hospital cardiac arrest and bystander
CPR
quality were prospectively collected from September 2010 to December 2015. The primary outcome was the proportion of high‐quality bystander
CPR
. During the study period, 57 173 residents (14.7%) completed the chest compression–only
CPR
training and 32 423 (8.3%) completed conventional
CPR
training. The proportion of bystander
CPR
performed did not change (from 43.3% in 2010 to 42.0% in 2015;
P
for trend=0.915), but the proportion of high‐quality bystander
CPR
delivery increased from 11.7% in 2010 to 20.7% in 2015 (
P
for trend=0.015). The 1‐year increment was associated with high‐quality bystander
CPR
(adjusted odds ratio, 1.461; 95% CI, 1.055–2.024). Bystanders who previously experienced
CPR
training were 3.432 times (95% CI, 1.170–10.071) more likely to perform high‐quality
CPR
than those who did not.

Conclusions

We trained 23.0% of the residents in the medium‐sized city of Osaka, Japan, and demonstrated that the proportion of high‐quality
CPR
performed on the scene increased gradually, whereas that of bystander
CPR
delivered overall remained stable.
Public Awareness of Stroke and the Appropriate Responses in China
Authors: Li Shengde , Cui Li-Ying , Anderson Craig , Zhu Suiqiang , Xu Ping , Wei Tiemin , Luo Yun , Chen Shengli , Jiang Nan , Hong Yuehui , Liu Weidong , Li Jian , Gao Chunpeng , Yu Chengdong , Shan Guangliang , Wang Longde , Peng Bin , Liu Dan , Xie Dongmei , Wei Fei , Wu Guanghui , Li Hongyan , Luo Hua , Min Jie , Tang Jinhai , Sun Jun , Li Luoqing , Yao Qi , Liu Shilin , Shi Wei , Yan Wei , Yu Xiaofei , Luo Xiaopeng , Peng Xiaoxiang , Zhang Ya , Gao Yang , Peng Ye , Xue Yongling , Lin Zhi ,   on behalf of the FAST-RIGHT study group
Published: January 2019

Background and Purpose—

Early presentation is critical for receiving effective reperfusion therapy for acute ischemic stroke, therefore, we undertook a national survey of awareness and responses to acute stroke symptoms in China.

Methods—

We undertook a cross-sectional community-based study of 187 723 adults (age ≥40 years) presenting to 69 administrative areas across China between January 2017 and May 2017 to determine the national stroke recognition rate and the correct action rate. Multivariable logistic regression models were used to identify factors associated with stroke recognition and intention-to-avail emergency medical services.

Results—

Estimates of stroke recognition rate and correct action rate were 81.9% (153 675/187 723) and 60.9% (114 380/187 723), respectively, but these rates varied widely by sociodemographic status, region, and stroke risk. Approximately one-third of participants who recognized a stroke failed to call emergency medical service. Low likelihood of emergency medical service use was associated with younger age (40–59 years), being male, rural location, (regions of east, south, and northwest China), high body mass index (≥24), low education (primary school or below), low personal income (<US $731 per annum), living with immediate family, having multiple children (≥2), having a friend with stroke, exposure to less avenues to learn about stroke, nonsmoking, regular exercise, unknown family history, and no history of cardiovascular disease. Intention of calling emergency medical service was strongly related to awareness of stroke (odds ratio 2.05; 95% CI, 2.00–2.10;
P
<0.001).

Conclusions—

Substantial discrepancies exist between stroke recognition and correct action and not all stroke patients know the appropriate responses. Further, national stroke educational programs with specific plans targeting different groups are needed, which do not solely focus on stroke recognition, but also on the appropriate responses at the time of a stroke.
CHOCO-JEX: A Research Experiment Focused on the Chocó Low-Level Jet over the Far Eastern Pacific and Western Colombia
Authors: Yepes Johanna , Poveda Germán , Mejía John F. , Moreno Leonardo , Rueda Carolina
Published: January 2019

The ChocoJet Experiment (CHOCO-JEX) is an interinstitutional research program developed by the Universidad Nacional de Colombia, the General Maritime Directorate of the Ministry of National Defense of Colombia, the Colombian Air Force, and the Desert Research Institute. The main goal of CHOCO-JEX is to characterize the vertical structure of the low-level Chocó jet (ChocoJet) through observations and modeling. Thus, four 7-day intensive observation periods (IOPs) took place during different seasons in 2016, two over land and two over the far eastern Pacific off the coast of Colombia, including the deployment of upper-air soundings four times per day to monitor the predominant diurnal cycle and the synoptic and seasonal variability. Preliminary results show deeper westerly moisture flow and a stronger diurnal cycle over land than over ocean. IOP4 provides the first observational evidence of the southwesterly ChocoJet with mean winds of 5 m s–1. Diurnal cycles of zonal wind are coherent with mountain–valley and sea–land breezes at low levels and the easterly flow is predominant at midlevels. Potential temperature anomalies appear to be related to gravity waves that modulate the diurnal cycle of precipitation in the region.