European Journal of Clinical Investigation (Eur J Clin Investig)

Publisher: European Society for Clinical Investigation, Wiley

Journal description

The Journal of the European Society for Clinical Investigation. The European Journal of Clinical Investigation publishes papers in the field of clinical investigation, provided they contribute to the advancement of knowledge in this field. The term 'clinical investigation' is interpreted widely and includes studies relevant to humans in health or disease, including such studies that may have taken place with animals.

Current impact factor: 2.73

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 2.734
2013 Impact Factor 2.834
2012 Impact Factor 3.365
2011 Impact Factor 3.018
2010 Impact Factor 2.736
2009 Impact Factor 2.643
2008 Impact Factor 2.784
2007 Impact Factor 2.701
2006 Impact Factor 2.847
2005 Impact Factor 2.684
2004 Impact Factor 2.53
2003 Impact Factor 2.346
2002 Impact Factor 2.193
2001 Impact Factor 2.255
2000 Impact Factor 2.071
1999 Impact Factor 1.922
1998 Impact Factor 1.907
1997 Impact Factor 1.693
1996 Impact Factor 2.15
1995 Impact Factor 2.174
1994 Impact Factor 2.224
1993 Impact Factor 2.349
1992 Impact Factor 1.99

Impact factor over time

Impact factor

Additional details

5-year impact 2.74
Cited half-life 8.30
Immediacy index 0.58
Eigenfactor 0.01
Article influence 0.83
Website European Journal of Clinical Investigation website
Other titles European journal of clinical investigation (Online)
ISSN 1365-2362
OCLC 46653881
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details


  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • Some journals have separate policies, please check with each journal directly
    • On author's personal website, institutional repositories, arXiv, AgEcon, PhilPapers, PubMed Central, RePEc or Social Science Research Network
    • Author's pre-print may not be updated with Publisher's Version/PDF
    • Author's pre-print must acknowledge acceptance for publication
    • Non-Commercial
    • Publisher's version/PDF cannot be used
    • Publisher source must be acknowledged with citation
    • Must link to publisher version with set statement (see policy)
    • If OnlineOpen is available, BBSRC, EPSRC, MRC, NERC and STFC authors, may self-archive after 12 months
    • If OnlineOpen is available, AHRC and ESRC authors, may self-archive after 24 months
    • Publisher last contacted on 07/08/2014
    • This policy is an exception to the default policies of 'Wiley'
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Blood pressure (BP) and metabolic response to thiazide diuretics might be varied in patients with different hypertension subtypes and ethnicities. This study aimed to investigate the response of BP and metabolic profiles to short-term thiazide treatment in an Asian cohort with different hypertension subtypes. Design: Serial ethnic Chinese non-diabetic subjects with hypertension were evaluated. After diet instruction and lifestyle modification for 2 weeks, patients who still had elevated systolic BP (SBP≥140 mmHg) and/or diastolic BP (DBP≥90 mmHg) were given 50 mg of hydrochlorothiazide daily for 2 weeks. The responses of BP and metabolic profiles were evaluated before and after treatment according to the patient's baseline BP subtype - isolated systolic hypertension (ISH), systolo-diastolic hypertension (SDH), and isolated diastolic hypertension (IDH). Results: Hydrochlorothiazide treatment significantly reduced the BP in all 92 patients (62 males, aged 45.7 ± 9.6 years) irrespective of their baseline BP subtypes. In the patients with SDH (n=39) or IDH (n=40), hydrochlorothiazide treatment significantly increased serum adiponectin (P=0.001 and 0.007, respectively) and reduced asymmetric dimethylarginine levels (P<0.001, in both groups). Serum cholesterol (P=0.027) and fasting blood sugar levels (P=0.044) were significantly improved only in the IDH patients. Furthermore, IDH was independently associated with changes in fasting blood sugar (β=-11.178, P=0.022) and cholesterol (β=-22.654, P=0.027). Conclusions: The characteristics of the Asian hypertensive patients with diastolic hypertension can present a favorable metabolic response to the short-term hydrochlorothiazide treatment. The potential positive effect on cardiovascular risk should be validated in long-term studies in this diastolic type of hypertension. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 11/2015; DOI:10.1111/eci.12571
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    ABSTRACT: Background: The risk of pancreatic cancer associated with incretin-based therapies is controversial. Methods: This study retrospectively analyzed the National Health Insurance database including patients with newly diagnosed type 2 diabetes mellitus at an age ≥25 years between 1999 and 2010. A total of 71,137 ever users of sitagliptin and 933,046 never users were followed for pancreatic cancer until December 31, 2011. A time-dependent approach was used to calculate incidence and estimate hazard ratios adjusted for propensity score using Cox regression. Results: During follow-up, 83 ever users and 3,658 never users developed pancreatic cancer, representing an incidence of 73.6 and 55.0 per 100,000 person-years, respectively. The adjusted hazard ratio (95% confidence intervals) for ever versus never users was 1.40 (1.13-1.75). The respective adjusted hazard ratio for the first, second, and third tertile of cumulative dose <14,700, 14,700-33,700 and >33,700 mg was 1.83 (1.28-2.62), 1.97 (1.41-2.76) and 0.72 (0.45-1.15). For average daily dose of <50, 50-99.9 and ≥100 mg, the respective hazard ratio was 3.10 (1.17-8.26), 1.01 (0.63-1.61) and 1.53 (1.18-1.97). Conclusions: Sitagliptin is significantly associated with a higher risk of pancreatic cancer, especially when the cumulative dose is <33,700 mg. The risk diminished in users with a higher cumulative dose. The daily dose of sitagliptin should better be kept <100 mg and its use should be reconsidered in patients who suffer from severe renal impairment and thus a daily dose of <50 mg is always recommended. Future studies are required to confirm the findings with more appropriate adjustment for smoking. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 11/2015; DOI:10.1111/eci.12570
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    ABSTRACT: In November 2015, the Council of the European Society of Clinical Investigation (ESCI) evaluated all clinical research articles published in the European Journal of Clinical Investigation (EJCI) from November 2014 to October 2015. Six articles by Chung and co-workers [1], Caballero et al. [2], de Beus et al. [3], Distelmaier et al. [4], Deetman et al. [5], Sciatti et al. [6] were selected for the final round and the Council on the basis of quality, novelty and impact selected for the 2016 ESCI Award for Best Clinical Research Article the study by Caballero and co-workers entitled "Influence of aortic regurgitation after TAVI on left ventricular filling pattern" [2]. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 11/2015; DOI:10.1111/eci.12569
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    ABSTRACT: Background: The role of neutrophils in the beginning and the progression of the atherosclerotic process did not receive much attention until the last years. On the contrary recent data, in both the experimental animals and humans, suggest important effects of these cells with possible clinical consequences. Materials and methods: This narrative review was based on the papers found on PubMed and MEDLINE up to July 2015. The search terms used were "neutrophil, atherosclerosis" in combination with "recruitment, chemokine, plaque destabilization, and pathophysiology". Results: Different models demonstrate the presence and the actions of neutrophils in the early steps of the atherogenesis confirming the fundamental role of these cells in the response of the innate immune system to different pathogens (in this context the modified lipoproteins). However also the late phases of the atherosclerotic process, in particular the destabilization of a mature plaque, seem to be modulated by the neutrophils, possibly through the interaction with recently discovered biological systems such as the endocannabinoids. Conclusions: The understanding of the mechanisms involved in the modulation exerted by neutrophils in atherosclerosis is pivotal in terms of the complete definition of the overall picture. This approach will certainly give us new targets and new pharmacological opportunities for the anti-inflammatory strategy of the cardiovascular prevention. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 11/2015; DOI:10.1111/eci.12566
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    ABSTRACT: Background: Chrousos syndrome is a rare pathologic condition characterized by generalized, partial resistance of target-tissues to glucocorticoids and caused by inactivating mutations of the human glucocorticoid receptor (hGR) gene. A novel case of Chrousos syndrome has been reported in a patient with adrenal incidentaloma, who harbored a heterozygous point mutation in the hGR gene, which resulted in threonine (T) to isoleucine (I) substitution at amino acid position 556 in the ligand-binding domain of the receptor. Objective: To delineate the molecular mechanisms through which the mutant receptor hGRαT556I causes Chrousos syndrome. Design and results: Compared with the wild-type receptor, the mutant receptor hGRαT556I demonstrated 50% reduction in its ability to transactivate glucocorticoid responsive genes and in the affinity for the ligand, 30% increase in the ability to transrepress the nuclear factor-κB target genes, and a 3,4-fold delay in the cytoplasmic-to-nuclear translocation. The mutant receptor hGRαT556I did not exert a dominant negative effect upon the hGRα-mediated transcriptional activity, it preserved its ability to bind to DNA and interacted with the glucocorticoid receptor-interacting protein 1 coactivator mostly through its activation function-1 domain. Structural biology studies revealed that the T556I mutation caused disruption of the hydrogen bond formed by the T556 with the =O group of P637 backbone, which resulted in significant relocation of the P637 bearing loop. This conformational alteration affected the local 3D arrangement of the receptor and, hence, the electrostatic surface of the region. Conclusions: The hGRαT556I causes Chrousos syndrome by impairing multiple steps of the glucocorticoid signal transduction pathway This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 11/2015; DOI:10.1111/eci.12563
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    ABSTRACT: Background: In patients with advanced refractory heart failure (HF) cardiac transplantation (HTX), conservative medical management and the implantation of a ventricular assist device (VAD) represent valuable options. The determination of the best therapeutic destination strategy for the individual patient remains a challenge. The aim of the present study was to assess the clinical outcome in advanced refractory HF patients either managed conservatively receiving optimal contemporary medical therapy ("conservative"), or underwent pulsatile flow VAD ("pVAD") or continuous flow VAD ("contVAD") implantation. Methods: 118 patients with INTERMACS profile >1 at baseline, who died, or fully completed a 24 month follow-up free from HTX were included into this retrospective analysis. All-cause mortality at 24 months was assessed and compared between the three groups. Results: 50 (42%) patients were managed conservatively, 25 (21%) received a pVAD and 43 (36%) a contVAD. NT-proBNP values were comparable between the three groups (median 4402 (IQR 2730-13390)pg/mL, 3580 (1602-6312)pg/mL and 3693 (2679-8065)pg/mL, p=0.256). Mean survival was 18.6 (95% CI 16.2-21.0) months for patients managed conservatively, 7.0 (3.9-10.0) for pVAD and 20.5 (18.2-22.8) for contVAD (overall Log-rank test p<0.001). Conservatively managed patients spent a mean of 22.4 (95%CI 22.1-22.8), pVAD 17.7 (15.4-20.1) and contVAD 21.6 (21.2-22.1) months out of hospital (conservative vs pVAD p<0.001; conservative vs contVAD p=0.015; pVAD vs contVAD p<0.001). Conclusion: In accordance with the literature, contVAD resulted in a significantly better clinical outcome than pVAD implantation. However, conservative management with current optimal medical therapy appears to remain a valuable option for patients with advanced HF. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 11/2015; DOI:10.1111/eci.12562
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    ABSTRACT: Recently, Ceron CS and Luison MR critically commented on our paper entitled "Serum lipids and cardiac function correlate with nitrotyrosine and MMP activity in CAD patients" (published in Eur J Clin Invest in 2015) in two major points. Here we respond to their letter in details and comment their criticisms on suitability of MMP activity assays in serum samples. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 11/2015; DOI:10.1111/eci.12560
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    ABSTRACT: Background: Hemodialysis patients suffer from chronic systemic inflammation and high incidence of cardiovascular disease. One cause for this may be the failure of diseased kidneys to eliminate immune mediators. Current hemodialysis treatment achieves insufficient elimination of proteins in the molecular weight range 15-45kD. Thus high cut-off dialysis might improve the inflammatory state. Design: In this randomized cross-over trial 43 hemodialysis patients were treated for three weeks with high cut-off or high-flux dialysis. Inflammatory plasma mediators, monocyte subpopulation distribution, and leucocyte gene expression were quantified. Results: High cut-off dialysis supplemented by a low-flux filter did not influence the primary end-point, expression density of CD162 on monocytes. Nevertheless, treatment reduced multiple immune mediators in plasma. Such reduction proved - at least for some markers - to be a sustained effect over the interdialytic interval. Thus, for example soluble TNF-Receptor1 concentration predialysis was reduced from median 13.3 (IQR 8.9-17.2) to 9.7 (IQR 7.5-13.2) ng/mL with high cut-off while remaining constant with high-flux treatment. The expression profile of multiple proinflammatory genes in leucocytes was significantly dampened. Treatment was well tolerated although albumin losses in high cut-off dialysis would be prohibitive against long-term use. Conclusions: The study shows for the first time that a dampening effect of high cut-off dialysis on systemic inflammation is achievable. Earlier studies had failed due to short study duration or insufficient dialysis efficacy. Removal of soluble mediators from the circulation influences cellular activation levels in leucocytes. Continued development of less albumin leaky membranes with similar cytokine elimination is justified. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12559
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    ABSTRACT: Context: Adipokines bearing the potential to cross the blood-brain-barrier (BBB) are promising candidates for the endocrine regulation of central nervous processes and of a postulated fat-brain axis. Objectives: Resistin and progranulin concentrations in paired serum and CSF samples of patients undergoing neurological evaluation and spinal puncture were investigated. Design: Samples of n=270 consecutive patients with various neurological diseases were collected without prior selection. Adipokine serum and CSF concentrations were measured by ELISA and serum and CSF routine parameters by standard procedures. Anthropometric data, medication and patient history were available. Results: Serum levels of resistin and progranulin were positively correlated among each other, with respective CSF levels, LDL cholesterol levels and markers of systemic inflammation. CSF resistin concentratons were generally low. Progranulin CSF concentrations and CSF/serum progranulin ratio were significantly higher in patients with infectious diseases, with disturbed BBB function and with elevated CSF cell count and presence of oligoclonal bands. Both adipokines are able to cross the BBB depending on a differing patency that increases with increasing grade of barrier dysfunction. Whereas resistin represents a systemic marker of inflammation, CSF progranulin levels strongly depend on the underlying disease and dysfunction of blood-CSF barrier. Conclusions: Resistin and progranulin represent novel and putative regulators of the fat-brain axis by their ability to cross the BBB under physiological and pathophysiological conditions. The presented data provide insight into the characteristics of BBB function regarding progranulin and resistin and the basis for future establishment of normal values for CSF concentrations and CSF/serum ratios. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12558
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    ABSTRACT: Background: A common complication of acute cardiac failure (AHF) is anemia, which negatively influences the clinical outcome. Causes of anemia include enhanced eryptosis, a suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation. Signaling triggering eryptosis include oxidative stress, increase of cytosolic Ca(2+) -activity ([Ca(2+) ]i ) and ceramide. The present study explored whether AHF is associated with accelerated eryptosis. Materials and methods: Erythrocytes were drawn from healthy volunteers (n = 10) and patients hospitalized for AHF (n=22). Phosphatidylserine exposure was estimated from annexin-V-binding, cell volume from forward scatter, [Ca(2+) ]i from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies and reactive oxygen species (ROS) abundance from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, as determined by flow cytometry. Results: In AHF-patients, hemoglobin concentration (11.5±0.5g/dl), and hematocrit (35.6±1.2%) were significantly lower than hemoglobin concentration (14.1±0.4g/dl), and hematocrit (40.1±1.0%) in healthy volunteers, even though reticulocyte number was significantly higher in AHF patients (2.3±0.3%) than in healthy volunteers (1.1±0.2%). The percentage of erythrocytes exposing phosphatidylserine was significantly higher in AHF patients (1.8±0.1%) than in healthy volunteers (1.4±0.2%). The forward scatter was significantly lower and the ROS abundance significantly larger in AHF patients than in healthy volunteers. In erythrocytes drawn from healthy volunteers, phosphatidylserine and ROS abundance was increased to significantly higher values following a 24 hours treatment with plasma from AHF patients than with plasma from healthy volunteers. Conclusion: AHF leads to anemia despite increased reticulocyte number and at least partially due to enhanced eryptosis. Underlying mechanisms include oxidative stress imposed by a plasma borne component. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12555
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    ABSTRACT: Background: Exercise preconditioning has been widely accepted as a being of safe and effective preventive measure for stroke. The purpose of this study was to investigate whether exercise preconditioning improves outcomes of ischemic stroke by promoting neuronal and glial expressing of heat shock protein (HSP) 20. Method: Adult male Sprague-Dawley rats (288 in number) were used to investigate the contribution of HSP20-containing neurons and HSP20-containing glial cells in the exercise-mediated neuroprotection in the stroke condition using middle cerebral artery occlusion. Result: Exercise preconditioning, in addition to increasing the numbers of both the HSP20-containg neurons (88±8 vs 43±4; n=8 each group; P<0.05) and the HSP20-containg astrocytes (102±10 vs 56±5; n=8; P<0.05) significantly attenuated stroke-induced brain infarct (140±9 mm3 vs 341±20 mm3; n=8 per group; P<0.01), neuronal apoptosis (20±5 vs 87±7; n=8 per group; n=8; P<0.01), glial apoptosis (29±5 vs 101±4; n=8; P<0.01), and neurological deficits (6.6±0.3 vs 11.7±0.8; n=8 per group; P<0.01). Reducing the numbers of both HSP20-containing neurons and HSP20-contaiing glia by intracerebral injection of pSUPER small interfering RNAί expressing HSP20 significantly reversed the beneficial effects of exercise preconditioning in attenuating stroke-induced cerebral infarct, neuronal and glial apoptosis, and neurological deficits. Conclusions: The numbers of both the HSP20-containing neurons and the HSP20-containing glia inversely correlated with the outcomes of ischemic stroke. In addition, preischemic treadmill exercise improves outcomes of ischemic stroke by increasing the numbers of both the HSP20-containing neurons and the HSP20-containing glia. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12551
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    ABSTRACT: The sympathetic nervous exerts a key role in cardiovascular homeostasis control by regulating cardiac output, systemic vascular resistance, heart rate, and blood pressure. Data collected during the past 30 years have unequivocally shown that in a considerable number of cardiovascular as well as non-cardiovascular disease there is a marked activation of the sympathetic nervous system which exerts in the long-term period unfavourable haemodynamic, metabolic, cardiovascular and renal effects. This paper will review the current knowledge on the alterations in sympathetic function described in cardiovascular disease, with particular focus on hypertension, heart failure and myocardial infarction. The consequences of the phoenomenon will be discussed together with its therapeutic implications. This will be done by examinining the impact of non-pharmacological as well as pharmacological interventions on sympathetic cardiovascular drive. The effects of new invasive approaches, such as carotid baroreceptor stimulation as well as renal nerves ablation, will be also briefly discussed. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12553
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    ABSTRACT: We sometimes encounter patients with microvascular angina (MVA), a disease characterized by anginal pain without abnormal coronary arteriographic findings or coronary spasm. More than 40 years have passed since MVA was first confirmed. The terms "syndrome X," "cardiac syndrome X," and "microvascular dysfunction" have also been used to describe conditions similar to MVA, but all with slightly different definitions. The cause of MVA seems almost certain to be organic and functional abnormalities of the small arteries of the heart. Patients with MVA are likely to suffer from endothelial dysfunction and other microvascular abnormalities of both the coronary and peripheral arteries. The major treatment of MVA has been medication, most often calcium channel blockers. The prognosis of MVA is generally excellent, although symptoms remain in many studies. Some MVA patients with accompanying hypertensive heart disease have gone on to develop progressive left ventricular dysfunction, with poor prognosis. The different definitions applied to the terms used to describe this condition, what we refer to here as MVA, can confound issues involved in diagnosis, prognosis, and proper treatment. Therefore, it is extremely important to distinguish primary MVA without underlying heart disease from secondary MVA to explore the disease mechanism and examine the clinical characteristics. It is more than 40 years since Likoff first confirmed this disease, therefore, all researchers know that strict diagnostic criteria for MVA should be immediately established. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12552
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    ABSTRACT: Transient Generalized Glucocorticoid Hypersensitivity is a rare disorder characterized by increased tissue sensitivity to glucocorticoids and compensatory hypoactivation of the hypothalamic-pituitary-adrenal axis. The condition itself and the underlying molecular mechanisms have not been elucidated. To present the clinical manifestations, endocrinologic evaluation and transcriptomic profile in a patient with Transient Generalized Glucocorticoid Hypersensitivity. A 9-year old girl presented with an 8-month history of clinical manifestations suggestive of Cushing syndrome. Endocrinologic evaluation revealed undetectable 08:00h ACTH (<1 pg/mL) and cortisol (0.025 μg/dL) concentrations, which remained decreased throughout the 24h period and did not respond to stimulation with ovine CRH. The disease gradually resolved spontaneously over the ensuing 3 months. Sequencing of the human glucocorticoid receptor gene revealed no mutations or polymorphisms. Western Blot analysis in peripheral blood mononuclear cells revealed equal protein expression of hGRα of the patient in the disease and post resolution phases compared with a control subject. Transcriptomic analysis in peripheral blood mononuclear cells in the disease and post resolution phases identified 903 differentially expressed genes. Of these, 106 genes were up-regulated and 797 were down-regulated in the disease compared with the resolution phase. Bioinformatics analysis on the differentially expressed gene networks revealed Nuclear Factor-κB as the predominant transcription factor influencing the expression of the majority of differentially expressed genes. Our findings indicate that a transient post-receptor defect, or a virus- or bacterium-encoded molecule may have enhanced glucocorticoid signal transduction, leading to transient generalized glucocorticoid hypersensitivity and hypoactivation of the HPA axis. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12554