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  • 1
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    Clinical significance of NTRK family gene expression in neuroblastomas
    Wiley ; 2012
    In:  Pediatric Blood & Cancer Vol. 59, No. 2 ( 2012-08), p. 226-232
    Details
    In: Pediatric Blood & Cancer, Wiley, Vol. 59, No. 2 ( 2012-08), p. 226-232
    Abstract: Neuroblastomas (NBs) are characterized by clinical heterogeneity, from spontaneous regression to relentless progression. The pattern of NTRK family gene expression contributes to these disparate behaviors. TrkA/ NTRK1 is expressed in favorable NBs that regress or differentiate, whereas TrkB/ NTRK2 and its ligand brain‐derived neurotrophic factor (BDNF) are co‐expressed in unfavorable NBs, representing an autocrine survival pathway. We determined the significance of NTRK family gene expression in a large, representative set of primary NBs. Patients and Methods We analyzed the expression of the following genes in 814 NBs using quantitative real‐time reverse transcriptase polymerase chain reaction (RT‐PCR): NTRK1 , NTRK2 , NTRK3 , P75/ NGFR , nerve growth factor ( NGF ), BDNF , IGFR1 , and EGFR . Expression (high vs. low) was dichotomized by median expression value and compared to clinical and biological variables as well as outcome. Results High NTRK1 expression was strongly correlated with favorable age, stage, MYCN status, histology, ploidy, risk group, and outcome ( P   〈  0.0001 for all). However, it did not add significantly to the panel of prognostic variables currently used for cooperative group trials. NTRK2 expression was associated with risk factors but not with outcome. High NGF expression was also associated with most risk factors and weakly with unfavorable outcome. Conclusions High expression of NTRK1 is strongly associated with favorable risk factors and outcome in a large, representative population of NB patients. It did not add significantly to the current risk prediction algorithm, but it may contribute to future expression classifiers. Indeed, prospective assessment of NTRK1 and NTRK2 expression will identify tumors that would be candidates for NTRK‐targeted therapy, either alone or in combination with conventional agents. Pediatr Blood Cancer 2012;59:226–232. © 2011 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    URL: Article
    DOI: 10.1002/pbc.v59.2
    DOI: 10.1002/pbc.23343
    Language: English
    Publisher: Wiley
    Publication Date: 2012
    detail.hit.zdb_id: 2130978-4
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  • 2
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    Association of physical activity and heart failure with preserved vs. reduced ejection fraction in the elderly: the Framingham Heart Study
    Wiley ; 2013
    In:  European Journal of Heart Failure Vol. 15, No. 7 ( 2013-07), p. 742-746
    Details
    In: European Journal of Heart Failure, Wiley, Vol. 15, No. 7 ( 2013-07), p. 742-746
    Abstract: Reduced physical activity is associated with increased risk of heart failure (HF) in middle‐aged individuals. We hypothesized that physical inactivity is also associated with greater HF risk in older individuals, and examined if the association was consistent for HF with preserved ejection fraction (HFPEF) vs. HF with a reduced ejection fraction (HFREF). Methods and results We evaluated 1142 elderly participants (mean age 76 years) from the Framingham Study without prior myocardial infarction and who attended a routine examination when daily physical activity was assessed systematically with a questionnaire. A composite score, the physical activity index (PAI), was calculated and modelled as tertiles, and related to incidence of HF, HFPEF, and HFREF on follow‐up using proportional hazards regression models adjusting for age and sex, and then additionally for standard HF risk factors. Participants with HF and EF 〈 45% vs. ≥45% were categorized as HFREF and HFPEF, respectively. On follow‐up (mean 10 years), 250 participants developed HF (108 with HFPEF, 106 with HFREF, 36 with unavailable EF). In age‐ and sex‐adjusted models, the middle and highest PAI tertiles were associated with a 15–56% lower risk of any HF, of HFREF, and of HFPEF, with a graded response across tertiles. In multivariable models, the association of higher PAI with lower risk of any HF and with HFPEF was maintained, whereas the association with HFREF was attenuated. Conclusions Our study of an older community‐based sample extends to the elderly and to HFPEF previous findings of a protective effect of physical activity on HF risk.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Article
    DOI: 10.1093/eurjhf/hft025
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 1500332-2
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  • 3
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    Biomarkers to identify and prevent new‐onset heart failure in the community
    Wiley ; 2016
    In:  European Journal of Heart Failure Vol. 18, No. 11 ( 2016-11), p. 1351-1352
    Details
    In: European Journal of Heart Failure, Wiley, Vol. 18, No. 11 ( 2016-11), p. 1351-1352
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    URL: Article
    DOI: 10.1002/ejhf.2016.18.issue-11
    DOI: 10.1002/ejhf.636
    Language: English
    Publisher: Wiley
    Publication Date: 2016
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  • 4
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    Distinct short-lived and long-lived antibody-producing cell populations
    Wiley ; 1986
    In:  European Journal of Immunology Vol. 16, No. 10 ( 1986), p. 1297-1301
    Details
    In: European Journal of Immunology, Wiley, Vol. 16, No. 10 ( 1986), p. 1297-1301
    Type of Medium: Online Resource
    ISSN: 0014-2980 , 1521-4141
    URL: Issue
    URL: Journal
    URL: Article
    DOI: 10.1002/eji.v16:10
    DOI: 10.1002/(ISSN)1521-4141
    DOI: 10.1002/eji.1830161018
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 1986
    detail.hit.zdb_id: 1491907-2
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  • 5
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    Sex‐specific associations of obesity and N‐terminal pro‐B‐type natriuretic peptide levels in the general population
    Wiley ; 2018
    In:  European Journal of Heart Failure Vol. 20, No. 8 ( 2018-08), p. 1205-1214
    Details
    In: European Journal of Heart Failure, Wiley, Vol. 20, No. 8 ( 2018-08), p. 1205-1214
    Abstract: Obese subjects have lower natriuretic peptide levels, but males and females have different anthropometric characteristics and fat distribution. Whether obesity‐associated lowering of natriuretic peptides differs among males and females is unknown. Therefore, we investigated sex‐specific associations of obesity and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) levels among adults in the general population. Methods and results Using 8260 participants (50.1% females) from the Prevention of REnal and Vascular ENd‐stage Disease (PREVEND) cohort, we evaluated the relationship of NT‐proBNP levels with obesity‐associated parameters, i.e. waist circumference (WC), body mass index (BMI) and body weight in the overall population, and in males and females separately. NT‐proBNP levels were higher in females (median, interquartile range: 50.5, 28.2–87.0 ng/L) than in males (24.3, 10.1–54.6 ng/L; P   〈  0.001). In the overall population, NT‐proBNP levels were significantly lower in heavier individuals and displayed a ‘U‐shaped’ relationship with increasing WC, but were not associated with BMI. After sex stratification, there was no significant association between NT‐proBNP concentrations and anthropometric measures in females. However, in males increasing WC and BMI were associated with higher NT‐proBNP levels ( P   〈  0.05) while increasing body weight was associated with slightly lower NT‐proBNP levels ( P   〈  0.05). Age strongly confounded the association of NT‐proBNP levels with obesity, and age‐associated increases in NT‐proBNP were significantly higher in males than in females ( P   〈  0.001). In multivariable adjusted analyses, the inverse association of obesity and NT‐proBNP levels was also significantly modified by sex: NT‐proBNP levels were lower with increasing WC, BMI and body weight among females compared with males ( P interaction   〈  0.05). After also accounting for BMI, abdominal obesity was associated with lower NT‐proBNP levels in females, but not in males ( P interaction   〈  0.001). Conclusions Natriuretic peptide deficiency in obesity mostly pertains to females with abdominal obesity, whereas the relationship between obesity and natriuretic peptides appears to be more complex in males.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    URL: Article
    DOI: 10.1002/ejhf.2018.20.issue-8
    DOI: 10.1002/ejhf.1209
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 6
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    Heart failure with preserved ejection fraction according to the HFA‐PEFF score in COVID ‐19 patients: clinical correlates and echocardiographic findings
    Wiley ; 2021
    In:  European Journal of Heart Failure Vol. 23, No. 11 ( 2021-11), p. 1891-1902
    Details
    In: European Journal of Heart Failure, Wiley, Vol. 23, No. 11 ( 2021-11), p. 1891-1902
    Abstract: Viral‐induced cardiac inflammation can induce heart failure with preserved ejection fraction (HFpEF)‐like syndromes. COVID‐19 can lead to myocardial damage and vascular injury. We hypothesised that COVID‐19 patients frequently develop a HFpEF‐like syndrome, and designed this study to explore this. Methods and results Cardiac function was assessed in 64 consecutive, hospitalized, and clinically stable COVID‐19 patients from April–November 2020 with left ventricular ejection fraction (LVEF) ≥50% (age 56 ± 19 years, females: 31%, severe COVID‐19 disease: 69%). To investigate likelihood of HFpEF presence, we used the HFA‐PEFF score. A low (0–1 points), intermediate (2–4 points), and high (5–6 points) HFA‐PEFF score was observed in 42%, 33%, and 25% of patients, respectively. In comparison, 64 subjects of similar age, sex, and comorbidity status without COVID‐19 showed these scores in 30%, 66%, and 4%, respectively (between groups: P  = 0.0002). High HFA‐PEFF scores were more frequent in COVID‐19 patients than controls (25% vs. 4%, P  = 0.001). In COVID‐19 patients, the HFA‐PEFF score significantly correlated with age, estimated glomerular filtration rate, high‐sensitivity troponin T (hsTnT), haemoglobin, QTc interval, LVEF, mitral E/A ratio, and H 2 FPEF score (all P   〈  0.05). In multivariate, ordinal regression analyses, higher age and hsTnT were significant predictors of increased HFA‐PEFF scores. Patients with myocardial injury (hsTnT ≥14 ng/L: 31%) vs. patients without myocardial injury, showed higher HFA‐PEFF scores [median 5 (interquartile range 3–6) vs. 1 (0–3), P   〈  0.001] and more often showed left ventricular diastolic dysfunction (75% vs. 27%, P   〈  0.001). Conclusion Hospitalized COVID‐19 patients frequently show high likelihood of presence of HFpEF that is associated with cardiac structural and functional alterations, and myocardial injury. Detailed cardiac assessments including echocardiographic determination of left ventricular diastolic function and biomarkers should become routine in the care of hospitalized COVID‐19 patients.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    URL: Article
    DOI: 10.1002/ejhf.v23.11
    DOI: 10.1002/ejhf.2210
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 7
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    Sex‐related differences in contemporary biomarkers for heart failure: a review
    Wiley ; 2020
    In:  European Journal of Heart Failure Vol. 22, No. 5 ( 2020-05), p. 775-788
    Details
    In: European Journal of Heart Failure, Wiley, Vol. 22, No. 5 ( 2020-05), p. 775-788
    Abstract: The use of circulating biomarkers for heart failure (HF) is engrained in contemporary cardiovascular practice and provides objective information about various pathophysiological pathways associated with HF syndrome. However, biomarker profiles differ considerably among women and men. For instance, in the general population, markers of cardiac stretch (natriuretic peptides) and fibrosis (galectin‐3) are higher in women, whereas markers of cardiac injury (cardiac troponins) and inflammation (sST2) are higher in men. Such differences may reflect sex‐specific pathogenic processes associated with HF risk, but may also arise as a result of differences in sex hormone profiles and fat distribution. From a clinical perspective, sex‐related differences in biomarker levels may affect the objectivity of biomarkers in HF management because what is considered to be ‘normal’ in one sex may not be so in the other. The objectives of this review are, therefore: (i) to examine the sex‐specific dynamics of clinically relevant HF biomarkers in the general population, as well as in HF patients; (ii) to discuss the overlap between sex‐related and obesity‐related effects, and (iii) to identify knowledge gaps to stimulate research on sex‐related differences in HF.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    URL: Article
    DOI: 10.1002/ejhf.v22.5
    DOI: 10.1002/ejhf.1771
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 8
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    The association of chronic kidney disease and microalbuminuria with heart failure with preserved vs. reduced ejection fraction
    Wiley ; 2017
    In:  European Journal of Heart Failure Vol. 19, No. 5 ( 2017-05), p. 615-623
    Details
    In: European Journal of Heart Failure, Wiley, Vol. 19, No. 5 ( 2017-05), p. 615-623
    Abstract: Chronic kidney disease ( CKD ) and microalbuminuria are associated with incident heart failure ( HF ), but their relative contributions to HF with preserved vs. reduced EF ( HFpEF and HFrEF ) are unknown. We sought to evaluate the associations of CKD and microalbuminuria with incident HF subtypes in the community‐based Framingham Heart Study ( FHS ). Methods and results We defined CKD as glomerular filtration rate 〈 60 mL /min/1.73 m 2 , and microalbuminuria as a urine albumin to creatinine ratio ( UACR ) ≥17 mg/g in men and ≥25 mg/g in women. We observed 754 HF events (324 HFpEF /326 HFrEF /104 unclassified) among 9889 FHS participants with serum creatinine measured (follow‐up 13 ± 4 years). In Cox models adjusted for clinical risk factors, CKD (prevalence = 9%) was associated with overall HF [hazard ratio ( HR ) 1.24, 95% confidence interval ( CI ) 1.01–1.51], but was not significantly associated with individual HF subtypes. Among 2912 individuals with available UACR (follow‐up 15 ± 4 years), 192 HF events (91 HFpEF /93 HFrEF /8 unclassified) occurred. Microalbuminuria (prevalence = 17%) was associated with a higher risk of overall HF ( HR 1.71, 95% CI 1.25–2.34) and HFrEF ( HR 2.10, 95% CI 1.35–3.26), but not HFpEF ( HR 1.26, 95% CI 0.78–2.03). In cross‐sectional analyses, microalbuminuria was associated with LV systolic dysfunction (odds ratio 3.19, 95% CI 1.67–6.09). Conclusions Microalbuminuria was associated with incident HFrEF prospectively, and with LV systolic dysfunction cross‐sectionally in a community‐based sample. In contrast, CKD was modestly associated with overall HF but not differentially associated with HFpEF vs. HFrEF . The mechanisms responsible for the relationship of microalbuminuria to future development of HFrEF warrant further investigation.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    URL: Article
    DOI: 10.1002/ejhf.2017.19.issue-5
    DOI: 10.1002/ejhf.778
    Language: English
    Publisher: Wiley
    Publication Date: 2017
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  • 9
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    Predictors and outcomes of heart failure with mid‐range ejection fraction
    Wiley ; 2018
    In:  European Journal of Heart Failure Vol. 20, No. 4 ( 2018-04), p. 651-659
    Details
    In: European Journal of Heart Failure, Wiley, Vol. 20, No. 4 ( 2018-04), p. 651-659
    Abstract: While heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid‐range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community. Methods and results We pooled data from four community‐based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41–49%], HFpEF (EF ≥50%), and HFrEF (EF ≤40%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12 years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P  ≤ 0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin‐C, and high‐sensitivity troponin ( P  ≤ 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence interval (CI) 1.81–2.20] than of HFmrEF (HR 1.51, 95% CI 1.20–1.90, P  = 0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95% CI 1.41–1.73, P  = 0.68 for difference). All‐cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person‐years, P  = 0.02), but comparable to that of HFrEF (46 events per 1000 person‐years, P  = 0.78). Conclusions We found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    URL: Article
    DOI: 10.1002/ejhf.2018.20.issue-4
    DOI: 10.1002/ejhf.1091
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 10
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    Preclinical Alterations in Myocardial Microstructure in People with Metabolic Syndrome
    Wiley ; 2017
    In:  Obesity Vol. 25, No. 9 ( 2017-09), p. 1516-1522
    Details
    In: Obesity, Wiley, Vol. 25, No. 9 ( 2017-09), p. 1516-1522
    Abstract: Metabolic syndrome (MetS) can lead to myocardial fibrosis, diastolic dysfunction, and eventual heart failure. This study evaluated alterations in myocardial microstructure in people with MetS by using a novel algorithm to characterize ultrasonic signal intensity variation. Methods Among 254 participants without existing cardiovascular disease (mean age 42 ± 11 years, 75% women), there were 162 with MetS, 47 with obesity without MetS, and 45 nonobese controls. Standard echocardiography was performed, and a novel validated computational algorithm was used to investigate myocardial microstructure based on sonographic signal intensity and distribution. The signal intensity coefficient (SIC [left ventricular microstructure]) was examined. Results The SIC was significantly higher in people with MetS compared with people with ( P   〈  0.001) and without obesity ( P  = 0.04), even after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, and the ratio of triglyceride (TG) to high‐density lipoprotein (HDL) cholesterol ( P   〈  0.05 for all). Clinical correlates of SIC included TG concentrations ( r  = 0.21, P  = 0.0007) and the TG/HDL ratio ( r  = 0.2, P  = 0.001). Conclusions This study's findings suggest that preclinical MetS and dyslipidemia in particular are associated with altered myocardial signal intensity variation. Future studies are needed to determine whether the SIC may help detect subclinical diseases in people with metabolic disease, with the ultimate goal of targeting preventive efforts.
    Type of Medium: Online Resource
    ISSN: 1930-7381 , 1930-739X
    URL: Issue
    URL: Article
    DOI: 10.1002/oby.v25.9
    DOI: 10.1002/oby.21936
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2027211-X
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