bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher left ventricular mass–wall stress–heart rate product and outcome in aortic valve stenosis
Authors: Gerdts Eva , Saeed Sahrai , Midtbø Helga , Rossebø Anne , Chambers John Boyd , Einarsen Eigir , Bahlmann Edda , Devereux Richard 
Published: June 2019

ObjectiveWhether increased myocardial oxygen demand could help explain the association of left ventricular (LV) hypertrophy with higher adverse event rate in patients with aortic valve stenosis (AS) is unknown.MethodsData from 1522 patients with asymptomatic mostly moderate AS participating in the Simvastatin-Ezetimibe in AS study followed for a median of 4.3 years was used. High LV mass–wall stress–heart rate product was identified as >upper 95% CI limit in normal subjects. The association of higher LV mass–wall stress–heart rate product with major cardiovascular (CV) events, combined CV death and hospitalised heart failure and all-cause mortality was tested in Cox regression analyses, and reported as HR and 95% CI.ResultsHigh LV mass–wall stress–heart rate product was found in 19% at baseline, and associated with male sex, higher body mass index, hypertension, LV hypertrophy, more severe AS and lower LV ejection fraction (all p<0.01). Adjusting for these confounders in time-varying Cox regression analysis, 1 SD higher LV mass–wall stress–heart rate product was associated with higher HR of major CV events (HR 1.16(95% CI 1.06 to 1.29)), combined CV death and hospitalised heart failure (HR 1.29(95% CI 1.09 to 1.54)) and all-cause mortality (HR 1.34(95% CI 1.13 to 1.58), all p<0.01).ConclusionIn patients with initially mild–moderate AS, higher LV mass–wall stress–heart rate product was associated with higher mortality and heart failure hospitalisation. Our results suggest that higher myocardial oxygen demand is contributing to the higher adverse event rate reported in AS patients with LV hypertrophy.Trial registration numberNCT000092677;Post-results.
Fat‐Specific Protein 27 Regulation of Vascular Function in Human Obesity
Authors: Karki Shakun , Farb Melissa G. , Sharma Vishva M. , Jash Sukanta , Zizza Elaina J. , Hess Donald T. , Carmine Brian , Carter Cullen O. , Pernar Luise I. , Apovian Caroline M. , Puri Vishwajeet , Gokce Noyan 
Published: June 2019

Background

Pathophysiological mechanisms that connect obesity to cardiovascular disease are incompletely understood. FSP27 (Fat‐specific protein 27) is a lipid droplet‐associated protein that regulates lipolysis and insulin sensitivity in adipocytes. We unexpectedly discovered extensive
FSP
27 expression in human endothelial cells that is downregulated in association with visceral obesity. We sought to examine the functional role of
FSP
27 in the control of vascular phenotype.

Methods and Results

We biopsied paired subcutaneous and visceral fat depots from 61 obese individuals (body mass index 44±8 kg/m
2
, age 48±4 years) during planned bariatric surgery. We characterized depot‐specific
FSP
27 expression in relation to adipose tissue microvascular insulin resistance, endothelial function and angiogenesis, and examined differential effects of
FSP
27 modification on vascular function. We observed markedly reduced vasodilator and angiogenic capacity of microvessels isolated from the visceral compared with subcutaneous adipose depots. Recombinant
FSP
27 and/or adenoviral
FSP
27 overexpression in human tissue increased endothelial nitric oxide synthase phosphorylation and nitric oxide production, and rescued vasomotor and angiogenic dysfunction (
P
<0.05), while si
RNA
‐mediated
FSP
27 knockdown had opposite effects. Mechanistically, we observed that
FSP
27 interacts with vascular endothelial growth factor‐A and exerts robust regulatory control over its expression. Lastly, in a subset of subjects followed longitudinally for 12±3 months after their bariatric surgery, 30% weight loss improved metabolic parameters and increased angiogenic capacity that correlated positively with increased
FSP
27 expression (
r
=0.79,
P
<0.05).

Conclusions

Our data strongly support a key role and functional significance of
FSP
27 as a critical endogenous modulator of human microvascular function that has not been previously described.
FSP
27 may serve as a previously unrecognized regulator of arteriolar vasomotor capacity and angiogenesis which are pivotal in the pathogenesis of cardiometabolic diseases linked to obesity.
Therapeutic Effect of Targeting Branched‐Chain Amino Acid Catabolic Flux in Pressure‐Overload Induced Heart Failure
Authors: Chen Mengping , Gao Chen , Yu Jiayu , Ren Shuxun , Wang Menglong , Wynn R. Max , Chuang David T. , Wang Yibin , Sun Haipeng 
Published: June 2019

Background
Branched‐chain amino acid (BCAA) catabolic defect is an emerging metabolic hallmark in failing hearts in human and animal models. The therapeutic impact of targeting BCAA catabolic flux under pathological conditions remains understudied.

Methods and Results
BT2 (3,6‐dichlorobenzo[b]thiophene‐2‐carboxylic acid), a small‐molecule inhibitor of branched‐chain ketoacid dehydrogenase kinase, was used to enhance BCAA catabolism. After 2 weeks of transaortic constriction, mice with significant cardiac dysfunctions were treated with vehicle or BT2. Serial echocardiograms showed continuing pathological deterioration in left ventricle of the vehicle‐treated mice, whereas the BT2‐treated mice showed significantly preserved cardiac function and structure. Moreover, BT2 treatment improved systolic contractility and diastolic mechanics. These therapeutic benefits appeared to be independent of impacts on left ventricle hypertrophy but associated with increased gene expression involved in fatty acid utilization. The BT2 administration showed no signs of apparent toxicity.

Conclusions
Our data provide the first proof‐of‐concept evidence for the therapeutic efficacy of restoring BCAA catabolic flux in hearts with preexisting dysfunctions. The BCAA catabolic pathway represents a novel and potentially efficacious target for treatment of heart failure.
Dietary Pattern Specific Protein Biomarkers for Cardiovascular Disease: A Cross‐Sectional Study in 2 Independent Cohorts
Authors: Warensjö Lemming Eva , Byberg Liisa , Stattin Karl , Ahmad Shafqat , Lind Lars , Elmståhl Sölve , Larsson Susanna C. , Wolk Alicja , Michaëlsson Karl 
Published: June 2019

Background
Mechanisms related to the influence of diet on the development of cardiovascular disease are not entirely understood, and protein biomarkers may help to understand these pathways. Studies of biomarkers identified with multiplex proteomic methods and dietary patterns are largely lacking.

Methods and Results

Dietary patterns were generated through principal component analysis in 2 population‐based Swedish cohorts, the EpiHealth (EpiHealth study; n=20 817 men and women) and the SMCC (Swedish Mammography Cohort Clinical [n=4650 women]). A set of 184 protein cardiovascular disease biomarkers were measured with 2 high‐throughput, multiplex immunoassays. Discovery and replication multivariable linear regression analyses were used to investigate the associations between the principal component analysis–generated dietary patterns and the cardiovascular disease–associated protein biomarkers, first in the EpiHealth (n=2240) and then in the Swedish Mammography Cohort Clinical. Four main dietary patterns were identified in the EpiHealth, and 3 patterns were identified in the Swedish Mammography Cohort Clinical. The
healthy
and the
Western/traditional
patterns were found in both cohorts. In the EpiHealth, 57 protein biomarkers were associated with 3 of the dietary patterns, and 41 of these associations were replicated in the Swedish Mammography Cohort Clinical, with effect estimates ranging from 0.057 to 0.083 (
P
‐value range, 5.0×10
−2
–1.4×10
−9
) for each SD increase in the relative protein concentration. Independent associations were established between dietary patterns and the 21 protein biomarkers. Two proteins, myeloperoxidase and resistin, were associated with both the
healthy
and the
light meal
pattern but in opposite directions.

Conclusions
We have discovered and replicated independent associations between dietary patterns and 21 biomarkers linked to cardiovascular disease, which have a role in the pathways related to inflammation, endothelial and immune function, cell adhesion, and metabolism.
Early Rapid Decline in Kidney Function in Medically Managed Patients With Atherosclerotic Renal Artery Stenosis
Authors: Cooper Emily L. , Xie Yanmei , Nguyen Hanh , Brewster Pamela S. , Sholl Haden , Sharrett Megan , Ren Kaili , Chen Tian , Tuttle Katherine R. , Haller Steven T. , Jamerson Kenneth , Murphy Timothy P. , D'Agostino Ralph B. , Massaro Joseph M. , Henrich William , Cooper Christopher J. , Cutlip Donald E. , Dworkin Lance D. , Shapiro Joseph I. 
Published: June 2019

Background
Early rapid declines of kidney function may occur in patients with atherosclerotic renal artery stenosis with institution of medical therapy. The causes and consequences are not well understood.

Methods and Results

Patients enrolled in the medical therapy–only arm of the CORAL (Cardiovascular Outcomes With Renal Artery Lesions) study were assessed for a rapid decline (
RD
) in estimated glomerular filtration rate (
eGFR
), defined as a ≥30% decrease from baseline to either 3 months, 6 months, or both. In the medical therapy–only cohort,
eGFR
was available in 359 subjects at all time points, the subjects were followed for a median of 4.72 years, and 66 of 359 (18%) subjects experienced an early
RD
. Baseline log cystatin C (odds ratio, 1.78 [1.11–2.85];
P
=0.02), age (odds ratio, 1.04 [1.00–1.07];
P
<0.05), and Chronic Kidney Disease Epidemiology Collaboration creatinine
eGFR
(odds ratio, 1.86 [1.15–3.0];
P
=0.01) were associated with an early
RD
. Despite continued medical therapy only, the
RD
group had an improvement in
eGFR
at 1 year (6.9%;
P
=0.04). The
RD
and nondecline groups were not significantly different for clinical events and all‐cause mortality (
P
=0.78 and
P
=0.76, respectively). Similarly, renal replacement therapy occurred in 1 of 66 (1.5%) of the
RD
patients and in 6 of 294 (2%) of the nondecline patients. The regression to the mean of improvement in
eGFR
at 1 year in the
RD
group was estimated at 5.8±7.1%.

Conclusions
Early rapid declines in kidney function may occur in patients with renal artery stenosis when medical therapy is initiated, and their clinical outcomes are comparable to those without such a decline, when medical therapy only is continued.
Prevalence and determinants of vitamin D deficiency in infants and toddlers in the Netherlands: a pilot study
Authors: Hoevenaar-Blom Marieke P , Wielders Jos PM , Groeneveld Henk , de Leeuw Elly , Schmits Ruben JH , Pepermans Carolien , Pasker-de Jong Pieternel CM , Hogeman Paul HG 
Published: June 2019

Background Little is known of the vitamin D status of young infants and toddlers and its determinants in West Europe. The prevalence and determinants of vitamin D deficiency of children aged 6–48 months in the centre of the Netherlands (52°N) is investigated. Methods In a cross-sectional population study, randomly recruited infants and toddlers ( n = 150) were studied using an online questionnaire and a physical examination either in late summer ( n = 52) or in late winter ( n = 98). Vitamin D analysis was performed by capillary blood sampling using dried bloodspots plus LC-MS/MS. Results In late winter, 32% of the children were vitamin D deficient (<50 nmol/L 25OH vitamin D3) with 5% severely deficient (<25 nmol/L). In late summer, 2% were deficient. The odds of vitamin D deficiency were higher in children aged 24–48 months, for those not using formula milk and those not adhering to the supplementation guidelines. Conclusion One-third of Dutch infants and toddlers were found to be vitamin D deficient in late winter. Suggested strategies for raising the vitamin D status may include improving the adherence to supplementation, a sensible sun exposure or the use of fortified foods. Special attention is needed for the children aged 24–48 months.
Novel ketamine analogues cause a false positive phencyclidine immunoassay
Authors: Skaugen John M , Scoccimarro Anthony , Pizon Anthony F , Rymer Jacqueline A , Giannoutsos Spiros , Ekins Sean , Krasowski Matthew D , Tamama Kenichi 
Published: June 2019

Background Immunoassays are commonly used to test for drugs of abuse in patients in a variety of settings. The increasing prevalence of ‘designer’ drugs causes difficulties for the toxicology laboratory and may result in unexpected false positives and identification of unfamiliar compounds. Within the past decade, there have been a variety of ketamine and phencyclidine analogues identified, particularly as drugs of abuse. Method We present a case of intoxication with a novel ketamine analogue, deschloro-N-ethyl-ketamine, causing a false positive phencyclidine immunoassay. Additionally, we performed spiking studies and 2D molecular similarity calculations for deschloro-N-ethyl-ketamine, ketamine and three other analogues on the Siemens Viva-E EMIT-II phencyclidine assay to assess their cross-reactivity. Results Four of the tested compounds (deschloro-N-ethyl-ketamine, 3-methoxy-phencyclidine, 3-methoxy-eticyclidine and methoxetamine) cause false positive phencyclidine immunoassay results, while ketamine gives a negative result. The cross-reactivity data are in accord with the similarity calculations of these molecules, further validating the ability of 2D molecular similarity analysis to predict the molecular cross-reactivity in immunoassays. Conclusions The cross-reactivity data of phencyclidine and ketamine analogues presented in this study could help toxicology laboratories and clinicians in evaluating unexpected results, particularly when novel PCP and ketamine analogues are being considered.
Computed tomography findings and in-hospital mortality in patients with rupture of type B aortic dissection
Authors: Otsuka Tetsuhiro , Sueyoshi Eijun , Tasaki Yutaro , Uetani Masataka 
Published: June 2019

Background The relationships between the computed tomography (CT) findings and outcomes of patients with ruptured type B aortic dissection have not been clarified. Purpose To evaluate the initial CT findings of patients with ruptured type B aortic dissection and investigate the relationships between the initial CT findings and in-hospital mortality. Material and Methods This study was approved by the institutional review board. Thirty-three patients were diagnosed with ruptured Stanford type B aortic dissection at our hospital between 2007 and 2016 (21 men, 12 women; mean age = 76.1±10.7 years). We retrospectively evaluated the initial CT findings of ruptured type B aortic dissection and the relationships between clinical factors and in-hospital mortality using logistic regression analysis. Results Type B aortic dissections ruptured in the acute and chronic phases in 23 and 10 patients, respectively. The initial CT images showed various findings, including an open false lumen (58%), arch involvement (88%), hematomas in the pleural space (55%), hematomas in the pericardial space (18%), and the extravasation of vascular contrast material (12%). The mean maximum diameter of the affected aorta was 49.5 ± 16.1 mm. Among the 33 patients, 14 died at hospital. Female gender (hazard ratio = 10.284; 95% confidence interval [CI] = 1.61–65.54; P = 0.0136) and the presence of a hematoma in the pleural space (hazard ratio = 6.803; 95% CI = 1.07–43.24; P = 0.0421) were found to be predictors of in-hospital mortality. Conclusion Female gender and the presence of a hematoma in the pleural space are significant predictors of in-hospital mortality in patients with ruptured type B aortic dissection.
Levetiracetam for prophylactic treatment of pediatric migraine: A randomized double-blind placebo-controlled trial
Authors: Montazerlotfelahi Hadi , Amanat Man , Tavasoli Ali Reza , Agah Elmira , Zamani Gholam Reza , Sander Josemir W , Badv Reza Shervin , Mohammadi Mahmoud , Dehghani Mahdieh , Heidari Morteza , Hosseini Seyed Ahmad , Salehi Mona , Ashrafi Mahmoud Reza 
Published: June 2019

Introduction Few drugs are available for migraine prophylaxis in children. Levetiracetam is a broad-spectrum anti-seizure drug that has been suggested to be effective in reducing adult migraine episodes. We assessed the safety and efficacy of levetiracetam in the prevention of pediatric migraine. Methods A randomized double-blind placebo-controlled trial was performed. Eligible participants were aged 4–17 years old with at least four migrainous episodes monthly or had severe disabling or intolerable episodes. Primary endpoints were the mean changes in monthly frequency and intensity of headaches from the baseline phase to the last month of the double-blind phase. Safety endpoint was the adverse effects reported. Results Sixty-one participants (31 taking levetiracetam and 30 taking placebo) completed the study. All had a significant reduction in frequency and intensity of episodes that was significantly greater in the levetiracetam arm. Sixty eight percent of individuals in the treatment group reported more than 50% reduction of episodes at the end of the trial compared with 30% in the placebo group ( p-value: 0.007). Irritability, day-time sedation, and mild tic were reported. Conclusion Levetiracetam may be useful in migraine prevention and may decrease migraine episodes and severity. Trial Registration The study is prospectively registered with Iranian Registry of Clinical Trials; IRCT.ir, number IRCT2017021632603N1.
Positive experience with treatment is associated with better surgical outcome in trapeziometacarpal osteoarthritis
Authors: Tsehaie Jonathan , van der Oest Mark J. W. , Poelstra Ralph , Selles Ruud W. , Feitz Reinier , Slijper Harm P. , Hovius Steven E. R. , Porsius Jarry T. ,   the Hand-Wrist Study Group
Published: June 2019

The aim of this study was to investigate the association between patients’ experiences with trapeziometacarpal arthroplasty and treatment outcomes in terms of patient-reported outcome measures, grip and pinch strength. We included 233 patients who received a Weilby procedure for trapeziometacarpal osteoarthritis. Before surgery and 12 months after surgery, patients completed the Michigan Hand Outcomes Questionnaire, and their pinch and grip strengths were measured. At 3 months after surgery, a patient-reported experience measure was completed. Using regression analysis, significantly positive associations were found between the Michigan Hand questionnaire and the patient-reported experience measure, with the strongest significant associations being for patients’ experiences with information provision. No significant associations were found between the patients’ experience and strength outcomes. The results highlight the potential importance of positive experience with the treatment process to improve treatment outcomes in patients undergoing surgery for trapeziometacarpal osteoarthritis. Level of evidence: IV
Occult obstructive coronary artery disease is associated with prolonged cardiac troponin elevation following strenuous exercise
Authors: Kleiven Øyunn , Omland Torbjørn , Skadberg Øyvind , Melberg Tor H , Bjørkavoll-Bergseth Magnus F , Auestad Bjørn , Bergseth Rolf , Greve Ole J , Aakre Kristin M , Ørn Stein 
Published: June 2019

Background Sudden cardiac death among middle-aged recreational athletes is predominantly due to myocardial ischaemia. This study examined whether measuring cardiac troponin I and T (cTnI and cTnT) after strenuous exercise could identify occult obstructive coronary artery disease. Design Prospective observational study. Methods Subjects were recruited from 1002 asymptomatic recreational cyclists completing a 91-km mountain bike race (North Sea Race Endurance Exercise Study). No subject had known cardiovascular disease or took cardiovascular medication. Blood samples were collected within 24 h before and 3 h and 24 h after the race. Coronary computed tomography angiography was performed in 80 participants with the highest post-exercise cTnI and in 40 reference subjects with moderately elevated cTnI values. Results Study subjects ( N = 120) were 45 (36–52) years old and 74% were male. There were similar demographics in the High-cTnI group and the Reference group. The cTn concentrations were highest at 3 h post-race: cTnI, 224 (125–304) ng/L; cTnT, 89 (55–124) ng/L. Nine subjects had obstructive coronary artery disease on coronary computed tomography angiography, eight of whom were High-cTnI responders. Two subjects had myocardial bridging, both High-cTnI responders. Troponin concentrations at 24 h post-race were higher in subjects with obstructive coronary artery disease than in the rest of the cohort ( n = 109): cTnI, 151 (72–233) ng/L vs. 24 (19–82) ng/L, p = 0.005; cTnT, 39 (25–55) ng/L vs. 20 (14–31) ng/L, p = 0.002. The areas under the receiver operating characteristic curves for predicting obstructive coronary artery disease were 0.79, p = 0.005 (cTnI) and 0.82, p = 0.002 (cTnT). Conclusion In subjects with occult obstructive coronary artery disease there was a prolonged elevation of cTn following strenuous exercise.
Revisiting the obesity paradox in heart failure: Per cent body fat as predictor of biomarkers and outcome
Authors: Aimo Alberto , Januzzi James L , Vergaro Giuseppe , Clerico Aldo , Latini Roberto , Meessen Jennifer , Anand Inder S , Cohn Jay N , Gravning Jørgen , Ueland Thor , Nymo Ståle H , Brunner-La Rocca Hans-Peter , Bayes-Genis Antoni , Lupón Josep , de Boer Rudolf A , Yoshihisa Akiomi , Takeishi Yasuchika , Egstrup Michael , Gustafsson Ida , Gaggin Hanna K , Eggers Kai M , Huber Kurt , Tentzeris Ioannis , Ripoli Andrea , Passino Claudio , Emdin Michele 
Published: June 2019

Aims Obesity defined by body mass index (BMI) is characterized by better prognosis and lower plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure. We assessed whether another anthropometric measure, per cent body fat (PBF), reveals different associations with outcome and heart failure biomarkers (NT-proBNP, high-sensitivity troponin T (hs-TnT), soluble suppression of tumorigenesis-2 (sST2)). Methods In an individual patient dataset, BMI was calculated as weight (kg)/height (m) 2 , and PBF through the Jackson–Pollock and Gallagher equations. Results Out of 6468 patients (median 68 years, 78% men, 76% ischaemic heart failure, 90% reduced ejection fraction), 24% died over 2.2 years (1.5–2.9), 17% from cardiovascular death. Median PBF was 26.9% (22.4–33.0%) with the Jackson–Pollock equation, and 28.0% (23.8–33.5%) with the Gallagher equation, with an extremely strong correlation ( r = 0.996, p < 0.001). Patients in the first PBF tertile had the worst prognosis, while patients in the second and third tertile had similar survival. The risks of all-cause and cardiovascular death decreased by up to 36% and 27%, respectively, per each doubling of PBF. Furthermore, prognosis was better in the second or third PBF tertiles than in the first tertile regardless of model variables. Both BMI and PBF were inverse predictors of NT-proBNP, but not hs-TnT. In obese patients (BMI ≥ 30 kg/m2, third PBF tertile), hs-TnT and sST2, but not NT-proBNP, independently predicted outcome. Conclusion In parallel with increasing BMI or PBF there is an improvement in patient prognosis and a decrease in NT-proBNP, but not hs-TnT or sST2. hs-TnT or sST2 are stronger predictors of outcome than NT-proBNP among obese patients.