bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of Scar-Related Ventricular Tachycardia Circuits Using Ultra-High-Density Mapping
Authors: Martin Ruairidh , Maury Philippe , Bisceglia Caterina , Wong Tom , Estner Heidi , Meyer Christian , Dallet Corentin , Martin Claire A. , Shi Rui , Takigawa Masateru , Rollin Anne , Frontera Antonio , Thompson Nathaniel , Kitamura Takeshi , Vlachos Konstantinos , Wolf Michael , Cheniti Ghassen , Duchâteau Josselin , Massoulié Grégoire , Pambrun Thomas , Denis Arnaud , Derval Nicolas , Hocini Mélèze , Della Bella Paolo , Haïssaguerre Michel , Jaïs Pierre , Dubois Rémi , Sacher Frédéric 
Published: October 2018

Background:
Ventricular tachycardia (VT) with structural heart disease is dependent on reentry within scar regions. We set out to assess the VT circuit in greater detail than has hitherto been possible, using ultra-high-density mapping.

Methods:
All ultra-high-density mapping guided VT ablation cases from 6 high-volume European centers were assessed. Maps were analyzed offline to generate activation maps of tachycardia circuits. Topography, conduction velocity, and voltage of the VT circuit were analyzed in complete maps.

Results:

Thirty-six tachycardias in 31 patients were identified, 29 male and 27 ischemic. VT circuits and isthmuses were complex, 11 were single loop and 25 double loop; 3 had 2 entrances, 5 had 2 exits, and 15 had dead ends of activation. Isthmuses were defined by barriers, which included anatomic obstacles, lines of complete block, and slow conduction (in 27/36 isthmuses). Median conduction velocity was 0.08 m/s in entrance zones, 0.29 m/s in isthmus regions (
P
<0.001), and 0.11 m/s in exit regions (
P
=0.002). Median local voltage in the isthmus was 0.12 mV during tachycardia and 0.06 mV in paced/sinus rhythm. Two circuits were identifiable in 5 patients. The median timing of activation was 16% of diastole in entrances, 47% in the mid isthmus, and 77% in exits.

Conclusions:
VT circuits identified were complex, some of them having multiple entrances, exits, and dead ends. The barriers to conduction in the isthmus seem to be partly functional in 75% of circuits. Conduction velocity in the VT isthmus slowed at isthmus entrances and exits when compared with the mid isthmus. Isthmus voltage is often higher in VT than in sinus or paced rhythms.
Genetic Variants Influencing Plasma Renin Activity in Hypertensive Patients From the PEAR Study (Pharmacogenomic Evaluation of Antihypertensive Responses)
Authors: McDonough Caitrin W. , Magvanjav Oyunbileg , Sá Ana C.C. , El Rouby Nihal M. , Dave Chintan , Deitchman Amelia N. , Kawaguchi-Suzuki Marina , Mei Wenbin , Shen Yong , Singh Ravi Shankar Prasad , Solayman Mohamed , Bailey Kent R. , Boerwinkle Eric , Chapman Arlene B. , Gums John G. , Webb Amy , Scherer Steven E. , Sadee Wolfgang , Turner Stephen T. , Cooper-DeHoff Rhonda M. , Gong Yan , Johnson Julie A. 
Published: October 2018

Background:
Plasma renin is an important regulator of blood pressure (BP). Plasma renin activity (PRA) has been shown to correlate with variability in BP response to antihypertensive agents. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with baseline PRA using data from the PEAR study (Pharmacogenomic Evaluation of Antihypertensive Responses).

Methods:
Multiple linear regression analysis was performed in 461 whites and 297 blacks using an additive model, adjusting for age, sex, and ancestry-specific principal components. Top SNPs were prioritized by testing the expected direction of association for BP response to atenolol and hydrochlorothiazide. Top regions from the BP response prioritization were tested for functional evidence through differences in gene expression by genotype using RNA sequencing data. Regions with functional evidence were assessed for replication with baseline PRA in an independent study (PEAR-2).

Results:

Our top SNP rs3784921 was in the
SNN-TXNDC11
gene region. The G allele of rs3784921 was associated with higher baseline PRA (β=0.47;
P
=2.09×10
−6
) and smaller systolic BP reduction in response to hydrochlorothiazide (β=2.97; 1-sided
P
=0.006). In addition,
TXNDC11
expression differed by rs3784921 genotype (
P
=0.007), and rs1802409, a proxy SNP for rs3784921 (
r
2
=0.98–1.00), replicated in PEAR-2 (β=0.15; 1-sided
P
=0.038). Additional SNPs associated with baseline PRA that passed BP response prioritization were in/near the genes
CHD9, XIRP2,
and
GHR.

Conclusions:
We identified multiple regions associated with baseline PRA that were prioritized through BP response signals to 2 mechanistically different antihypertensive drugs.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00246519.
Outcomes of Contemporary Family Screening in Hypertrophic Cardiomyopathy
Authors: van Velzen Hannah G. , Schinkel Arend F.L. , Baart Sara J. , Oldenburg Rogier A. , Frohn-Mulder Ingrid M.E. , van Slegtenhorst Marjon A. , Michels Michelle 
Published: October 2018

Background:
Contemporary hypertrophic cardiomyopathy (HCM) family screening includes clinical evaluation and genetic testing (GT). This screening strategy requires the identification of a pathogenic mutation in the proband. Our aim was to examine the results of this HCM screening strategy.

Methods:
Between 1985 and 2016, 777 relatives of 209 probands were assessed in the context of HCM screening. Genotype-positive (G+) relatives and relatives without genetic testing (GT) underwent repeated clinical evaluations. In genotype-negative (G-) relatives mortality was assessed during follow-up.

Results:

A pathogenic mutation was identified in 72% of probands. After counseling, GT was performed in 620 (80%) relatives: 264 (43%) were G+ (age 41±18 y) and 356 (57%) were G- (age 48±17 y). At first screening, HCM was diagnosed in 98 (37%) G+ relatives and 28 (17%) relatives without GT (
p
<0.001). During 9 years follow-up of relatives diagnosed with HCM, 8 (6%) underwent septal reduction therapy, 16 (16%) received primary prevention ICDs, and cardiac mortality was 0.3%/year. During 7 years follow-up of relatives without HCM, 29 (16%) developed HCM. Survival at 5/10 years was 99%/95% in G+ relatives, 97%/94% in G- relatives (
p
=0.8), and 100%/100% in relatives without GT.

Conclusions:
HCM was identified in 30% of relatives at first screening, and 16% developed HCM during 7 years of repeated evaluation. GT led to a discharge from clinical follow-up in 46% of the study population. Survival in the relatives was good.
Hyperacute Monocyte Gene Response Patterns Are Associated With Lower Extremity Vein Bypass Graft Failure
Authors: Rehfuss Jonathan P. , DeSart Kenneth M. , Rozowsky Jared M. , O’Malley Kerri A. , Moldawer Lyle L. , Baker Henry V. , Wang Yaqun , Wu Rongling , Nelson Peter R. , Berceli Scott A. 
Published: October 2018

Background:
Despite being the definitive treatment for lower extremity peripheral arterial disease, vein bypass grafts fail in half of all cases. Early repair mechanisms after implantation, governed largely by the immune environment, contribute significantly to long-term outcomes. The current study investigates the early response patterns of circulating monocytes as a determinant of graft outcome.

Methods:
In 48 patients undergoing infrainguinal vein bypass grafting, the transcriptomes of circulating monocytes were analyzed preoperatively and at 1, 7, and 28 days post-operation.

Results:

Dynamic clustering algorithms identified 50 independent gene response patterns. Three clusters (64 genes) were differentially expressed, with a hyperacute response pattern defining those patients with failed versus patent grafts 12 months post-operation. A second independent data set, comprised of 96 patients subjected to major trauma, confirmed the value of these 64 genes in predicting an uncomplicated versus complicated recovery. Causal network analysis identified 8 upstream elements that regulate these mediator genes, and Bayesian analysis with a priori knowledge of the biological interactions was integrated to create a functional network describing the relationships among the regulatory elements and downstream mediator genes. Linear models predicted the removal of either
STAT3
(signal transducer and activator of transcription 3) or
MYD88
(myeloid differentiation primary response 88) to shift mediator gene expression levels toward those seen in successful grafts.

Conclusions:
A novel combination of dynamic gene clustering, linear models, and Bayesian network analysis has identified a core set of regulatory genes whose manipulations could migrate vein grafts toward a more favorable remodeling phenotype.
CETP (Cholesteryl Ester Transfer Protein) Concentration
Authors: Blauw Lisanne L. , Li-Gao Ruifang , Noordam Raymond , de Mutsert Renée , Trompet Stella , Berbée Jimmy F.P. , Wang Yanan , van Klinken Jan B. , Christen Tim , van Heemst Diana , Mook-Kanamori Dennis O. , Rosendaal Frits R. , Jukema J. Wouter , Rensen Patrick C.N. , Willems van Dijk Ko 
Published: October 2018

Background:
We aimed to identify independent genetic determinants of circulating CETP (cholesteryl ester transfer protein) to assess causal effects of variation in CETP concentration on circulating lipid concentrations and cardiovascular disease risk.

Methods:
A genome-wide association discovery and replication study on serum CETP concentration were embedded in the NEO study (Netherlands Epidemiology of Obesity). Based on the independent identified variants, Mendelian randomization was conducted on serum lipids (NEO study) and coronary artery disease (CAD; CARDIoGRAMplusC4D consortium).

RESULTS:

In the discovery analysis (n=4248), we identified 3 independent variants (
P
<5×10
−8
) that determine CETP concentration. These single-nucleotide polymorphisms were mapped to
CETP
and replicated in a separate subpopulation (n=1458). Per-allele increase (SE) in serum CETP was 0.32 (0.02) µg/mL for rs247616-C, 0.35 (0.02) µg/mL for rs12720922-A, and 0.12 (0.02) µg/mL for rs1968905-G. Combined, these 3 variants explained 16.4% of the total variation in CETP concentration. One microgram per milliliter increase in genetically determined CETP concentration strongly decreased high-density lipoprotein cholesterol (−0.23 mmol/L; 95% confidence interval, −0.26 to −0.20), moderately increased low-density lipoprotein cholesterol (0.08 mmol/L; 95% confidence interval, 0.00–0.16), and was associated with an odds ratio of 1.08 (95% confidence interval, 0.94–1.23) for CAD risk.

Conclusions:
This is the first genome-wide association study identifying independent variants that largely determine CETP concentration. Although high-density lipoprotein cholesterol is not a causal risk factor for CAD, it has been unequivocally demonstrated that low-density lipoprotein cholesterol lowering is proportionally associated with a lower CAD risk. Therefore, the results of our study are fully consistent with the notion that CETP concentration is causally associated with CAD through low-density lipoprotein cholesterol.
Relationship Between Enrolling Country Income Level and Patient Profile, Protocol Completion, and Trial End Points
Authors: Greene Stephen J. , Hernandez Adrian F. , Sun Jie-Lena , Butler Javed , Armstrong Paul W. , Ezekowitz Justin A. , Zannad Faiez , Ferreira João Pedro , Coles Adrian , Metra Marco , Voors Adriaan A. , Califf Robert M. , O’Connor Christopher M. , Mentz Robert J. 
Published: October 2018

Background:
Globalization of clinical trials fosters inclusion of higher and lower income countries, but the influence of enrolling country income level on heart failure trial performance is unclear. This study sought to evaluate associations between enrolling country income level, acute heart failure patient profile, protocol completion, and trial end points.

Methods and Results:

The ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial included 7141 patients with acute heart failure from 30 countries. Country income data in gross national income per capita in current US dollars from the year 2007 (ie, the year trial enrollment began) were abstracted from the World Bank. Patients were grouped by enrolling country income level (ie, high [>$11 455], upper middle [$3706–$11 455], lower middle [$936–$3705], and low [<$936]). Income data were available for 29 (97%) countries (N=7064). There were 3996 (57%), 1518 (21%), and 1550 (22%) patients from high-income, upper-middle–income, and lower-middle–income countries, respectively. There were no patients from low-income countries. Patients from lower-middle–income countries tended to be younger with fewer comorbidities and lower utilization of guideline-directed therapies. Rates of adverse events (13.8%) and protocol noncompletion (4.9%) during 180-day follow-up were highest among high-income countries (all
P
<0.01). After adjustment for race, geographic region, and clinical characteristics, compared with lower-middle–income countries, enrollment from higher income countries was associated with increased 30-day mortality or rehospitalization (high income: odds ratio, 1.70; 95% CI, 1.02–2.85; upper-middle-income: odds ratio, 2.16; 95% CI, 1.23–3.81), driven by higher rates of rehospitalization. Mortality was similar at 30 and 180 days. The association between higher country income and the 30-day composite end point was similar across geographic regions, with exception of Latin America (
P
for interaction, 0.03).

Conclusions:
In this global acute heart failure trial, patients from higher income countries had lower rates of protocol completion, higher rates of adverse events, and similar mortality rates. After adjustment for race, geographic region, and clinical factors, enrollment from a higher income country was associated with worse clinical outcomes, driven by higher rates of rehospitalization. Variation in enrolling country income level may influence study end points and trial performance independent of geographic region.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00475852.
Impact of Missing Stroke Severity Data on the Accuracy of Hospital Ischemic Stroke Mortality Profiling
Authors: Thompson Michael P. , Luo Zhehui , Gardiner Joseph , Burke James F. , Nickles Adrienne , Reeves Mathew J. 
Published: October 2018

Background:
The Centers for Medicare and Medicaid Services have proposed 30-day ischemic stroke risk-standardized mortality rates that include adjustment for stroke severity using the National Institute of Health Stroke Scale (NIHSS), which is often undocumented. We used simulations to quantify the effect of missing NIHSS data on the accuracy of hospital-level ischemic stroke risk-standardized mortality rate profiling for 100 hypothetical hospitals with different case volumes.

Methods and Results:
We generated simulated data sets of patients with NIHSS scores and other predictors of 30-day mortality based on empirical analysis of data from 7654 patients with ischemic stroke in the Michigan Stroke Registry. We assigned and rank-ordered a true (known) 30-day mortality rate to each hospital in the simulated data sets of N=100 hospitals with either low (100 patients with stroke), medium (300), or high (500) case volumes. We then estimated and rank-ordered 30-day risk-standardized mortality rates for the N=100 hospitals in each simulated data set using hierarchical logistic regression models. In each data set, we systematically varied the rate of missing NIHSS data and whether missing NIHSS data was independent (missing completely at random) or dependent (missing not at random) on the NIHSS score. With no missing NIHSS data, the Spearman correlation between the true hospital performance rank order assigned during data set generation and the estimated 30-day risk-standardized mortality rate rank order was 0.72, 0.88, and 0.91 in low, medium, and high volume hospitals, respectively. However, this fell to as low as 0.50, 0.71, and 0.79 as missing NIHSS data reached 70%.

Conclusions:
Missing NIHSS data had substantial detrimental effects on the accuracy of profiling of ischemic stroke mortality, especially in lower volume hospitals. Even with complete NIHSS documentation, significant limitations in ischemic stroke mortality profiling remain.
Meta‐Analysis Global Group in Chronic (MAGGIC) Heart Failure Risk Score: Validation of a Simple Tool for the Prediction of Morbidity and Mortality in Heart Failure With Preserved Ejection Fraction
Authors: Rich Jonathan D. , Burns Jacob , Freed Benjamin H. , Maurer Mathew S. , Burkhoff Daniel , Shah Sanjiv J. 
Published: October 2018

Background

The Meta‐Analysis Global Group in Chronic Heart Failure (
MAGGIC
) mortality risk score, derived from a large sample of patients with heart failure (
HF
) across the spectrum of ejection fraction (
EF
), has not yet been externally validated in a well‐characterized
HF
with preserved
EF
cohort with adjudicated morbidity outcomes.

Methods and Results

We evaluated the
MAGGIC
risk score (composed of 13 clinical variables) in 407 patients with
HF
with preserved
EF
enrolled in a prospective registry and used Cox regression to evaluate its association with morbidity/mortality. We used receiver‐operating characteristic analysis to compare the predictive ability of the
MAGGIC
risk score with the more complex Seattle Heart Failure Model, and we determined the value of adding B‐type natriuretic peptide to the
MAGGIC
risk score for risk prediction. During a mean follow‐up time of 3.6±1.8 years, 28% died, 32% were hospitalized for
HF
, and 55% had a cardiovascular hospitalization and/or death. The
MAGGIC
score, a mean±
SD
of 18±7, was significantly associated with mortality (
P
<0.0001),
HF
hospitalizations (
P
<0.0001), and the combined end point of cardiovascular‐related hospitalizations or death (hazard ratio, 1.8 [95% confidence interval, 1.6–2.1], per 1‐
SD
increase in the
MAGGIC
score;
P
<0.0001). Receiver‐operating characteristic analyses showed that
MAGGIC
and Seattle Heart Failure Model performed similarly in predicting
HF
with preserved
EF
outcomes, but the
MAGGIC
score demonstrated better calibration for hospitalization outcomes. Further analyses showed that B‐type natriuretic peptide was additive to the
MAGGIC
risk score for predicting outcomes (
P
<0.01 by likelihood ratio test).

Conclusions

The
MAGGIC
risk score is a simple, yet powerful method of risk stratification for both morbidity and mortality in
HF
with preserved
EF
.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01030991.
The Menorah: Cult, History, and Myth Exhibiting the Past and Future of Catholic-Jewish Relations
Authors: Fine Steven 
Published: October 2018

AbstractLa Menorà: Culto, Storia E Mito, The Menorah: Worship, History and Myth was a monumental exhibition mounted by the Vatican Museums and the Jewish Museum of Rome in the Spring of 2017. Bringing together many of the most important artifacts relating to the history of the biblical lampstand in both Jewish and Christian traditions, this exhibition marks a milestone in Jewish-Catholic engagement, and was an active agent in that process. This article presents this act of museological diplomacy, describing many of its most significant artifacts as well as the historiographic challenges presented by this exhibition.
Systematic Review of Supraclavicular Artery Island Flap vs Free Flap in Head and Neck Reconstruction
Authors: Sukato Daniel C. , Timashpolsky Alisa , Ferzli George , Rosenfeld Richard M. , Gordin Eli A. 
Published: October 2018

ObjectiveThe aim of this systematic review is to compare the surgical outcomes of supraclavicular artery island flap (SCAIF) and free tissue transfer (FTT) in head and neck reconstruction.Data SourcesPubMed, Web of Science, and EMBASE databases.Review MethodsIndependent screening and data extraction were performed by 2 authors. Only studies that directly compared SCAIF and FTT were included. Data were pooled with random‐effects meta‐analysis to determine the standardized mean differences (SMDs), risk differences, and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistics. The Methodological Index for Non‐Randomized Studies tool was used to evaluate extent of bias in studies.ResultsThe initial query yielded 661 results, of which 4 comparative studies remained for final analysis. The pooled sample sizes for the SCAIF and FTT cohorts were 100 and 84, respectively. SCAIF was associated with reduction of operative time by a large effect size (SMD, 1.65; 95% confidence interval, 0.78‐2.52). The harvested flap areas and perioperative complications, including rates of total flap loss, partial flap necrosis, and recipient/donor site dehiscences, were comparable between the 2 procedures with low to high heterogeneity among studies.ConclusionSCAIF requires less operative time and has comparable short‐term perioperative results to FTT. The findings of this study support the viability of SCAIF as an alternative to FTT and provide evidence for its inclusion in the reconstructive armamentarium of major head and neck ablation and trauma.
Gross Pathology of Routine Pediatric Tonsillectomy Specimens: Optimizing the Value of Patient Care
Authors: Hobbs Elizabeth A. , Hanson Joshua A. , Nicholas Robert G. , Johnson Benjamin R. , Hawley Karen A. 
Published: October 2018

ObjectiveThis investigation seeks to evaluate the effect of gross pathologic analysis on our management of patients undergoing routine tonsillectomy and to evaluate charges and reimbursement.Study DesignRetrospective chart review from 2005 through 2016.SettingAcademic medical center.Subjects and MethodsParticipants were pediatric patients aged 14 years and younger undergoing tonsillectomy for either sleep‐disordered breathing or tonsillitis, with tonsillectomy specimens evaluated by pathology, and without any risk factors for pediatric malignancy. Records were reviewed for demographics, surgical indications, and pathology. Abnormal reports prompted an in‐depth review of the chart. Charges and reimbursement related to both hospital and professional fees for gross tonsil analysis were evaluated.ResultsFrom 2005 to 2016, 3183 routine pediatric tonsillectomy cases were performed with corresponding specimens that were sent for gross analysis revealing no significant pathologic findings; 1841 were males and 1342 were females. Ten cases underwent microscopy by pathologist order, revealing normal tonsillar tissue. The mean charge per patient for gross analysis was $60.67 if tonsils were together as 1 specimen and $77.67 if tonsils were sent as 2 separate specimens; respective reimbursement amounts were $28.74 and $35.90.ConclusionsGross pathologic analysis did not change our management of routine pediatric tonsillectomy patients. Foregoing the practice at our institution would eliminate $19,171.72 to $24,543.72 in charges and $9081.40 to $11,344.40 in reimbursement per year. Eliminating this test would improve the value of patient care by saving health care resources without compromising clinical outcomes.