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

2016 Impact Factor Available summer 2017
2014 / 2015 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: To maintain the balance between the demand of the body and supply (cardiac output), cardiac performance is tightly regulated via the parasympathetic and sympathetic nervous systems. In heart failure, cardiac output (supply) is decreased due to pathologic remodeling of the heart. To meet the demands of the body, the sympathetic system is activated and catecholamines stimulate β-adrenergic receptors (β-ARs) to increase contractile performance and cardiac output. Although this is beneficial in the acute phase, chronic β-ARs stimulation initiates a cascade of alterations at the cellular level, resulting in a diminished contractile performance of the heart. Materials and methods: This narrative review includes results from previously published systematic reviews and clinical and basic research publications obtained via PubMed up to May 2015. Results: We discuss the alterations that occur during sustained β-AR stimulation in diseased myocardium, and emphasize the consequences of β-AR overstimulation for cardiac function. In addition, current treatment options as well as future therapeutic strategies to treat patients with heart failure to normalize consequences of β-AR overstimulation are discussed. Conclusions: The heart is able to protect itself from chronic stimulation of the β-ARs via desensitization and reduced membrane-availability of the β-ARs. However, ultimately this leads to an impaired downstream signalling and decreased protein kinase A (PKA)-mediated protein phosphorylation. β-blockers are widely used to prevent β-AR overstimulation and restore β-ARs in the failing hearts. However novel and more specific therapeutic treatments are needed to improve treatment of HF in the future. This article is protected by copyright. All rights reserved.
    No preview · Article · Feb 2016 · European Journal of Clinical Investigation
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    ABSTRACT: Objective: N(ε)-(carboxymethyl)lysine (CML) is one of the major advanced glycation end products in both diabetics and non-diabetics. CML depositions in the microvasculature, has recently been linked to the etiology of acute myocardial infarction and cognitive impairment in Alzheimer's disease, possibly related to local enhancement of inflammation and oxidative processes. We hypothesised that CML deposition in the microvasculature of the heart and brain is age-induced and that it could be inhibited by a diet intervention with docosahexaenoic acid (DHA), an omega-3 fatty acid known for its anti-inflammatory and anti-oxidative actions. Material and methods: ApoE -/- mice (n=50) were fed a western diet and were sacrificed after 40, 70 and 90 weeks. Part of these mice (n=20) were fed a western diet enriched with DHA from 40 weeks on. CML in cardiac and cerebral microvessels was quantified using immunohistochemistry. Results: Cardiac microvascular CML depositions significantly increased with an immunohistochemical score of 11.85 [5.92-14.60] at 40 weeks, to 33.17 [17.60-47.15] at 70 weeks (p=0.005). At the same time points, cerebral microvascular CML increased from 6.45; [4.78-7.30] to 12.99; [9.85-20.122] (p=0.003). DHA decreased CML in the intramyocardial vasculature at both 70 and 90 weeks, significant at 70 weeks (33.17;[17.60-47.15] vs. 14.73;[4.44-28.16] p=0.037). No such effects were found in the brain. Conclusions: Accumulation of N(ε)-(carboxymethyl)lysine in the cerebral and cardiac microvasculature is age-induced and is prevented by docosahexaenoic acid in the intramyocardial vessels of ApoE -/- mice. This article is protected by copyright. All rights reserved.
    No preview · Article · Feb 2016 · European Journal of Clinical Investigation
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    ABSTRACT: Background: Soluble urokinase plasminogen activator receptor (suPAR) is a stable inflammatory biomarker. In patients, suPAR is a marker of disease presence, severity and prognosis. In the general population, suPAR is predictive of disease development, such as diabetes and cardiovascular disease and, in smokers, predictive of long-term lung cancer development. Whether smoking cessation impacts the suPAR level is unknown. Materials and methods: Forty-eight smokers were randomized into three groups of 16: 1) continued to smoke 20 cigarettes per day, 2) refrained from smoking and used transdermal nicotine patches and 3) refrained from smoking and used placebo patches. Non-smokers were included for comparison. suPAR and C-reactive protein (CRP) levels were measured by ELISA. Results: At baseline, the suPAR level was significantly higher in the 48 smokers (median 3.2 ng/ml, IQR (2.5-3.9)) than in 46 never smokers (1.9 ng/ml (1.7-2.2)). In smokers randomised to smoking cessation, suPAR levels after four weeks of stopping were decreased and no longer significantly different from the never smokers values. SuPAR decreased in both those who received a placebo as well as nicotine patch. Interestingly, those with the highest suPAR level at time of smoking were also those with the highest level of suPAR after smoking cessation. In contrast, smoking or smoking cessation had no influence on CRP levels. Conclusion: Our study suggest that the suPAR level may aid to personalize the risk of smoking by identifying those smokers with the highest risk of developing disease and who may have the most benefit of smoking cessation. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · European Journal of Clinical Investigation
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    ABSTRACT: Background: The predictive role of Doppler Renal Resistive Index (RRI) for mortality was shown in chronic kidney disease. In selected populations of intensive care unit (ICU) RRI predicts Acute Kidney Injury (AKI) occurrence and anticipates persistent AKI. No data are available about mortality. We investigated whether RRI assay at AKI diagnosis could predict AKI mortality in a 10-bed mixed medical-surgical and trauma ICU of a tertiary referral teaching hospital.The association between RRI and persistent AKI at discharge was investigated. Methods: One hundred-25 out of 1512 patients admitted from January 2010 to March 2013 who developed AKI during ICU stay were enrolled. Kidney function was evaluated daily according to risk, injury, failure, loss and end stage (RIFLE) criteria. At AKI diagnosis we measured RRI. The association between RRI at AKI diagnosis and ICU-death or persistent AKI at ICU discharge was analyzed by multivariable logistic regression analysis. Results: At AKI diagnosis RRI was 0.77 (0.70-0.88) in survivors and 0.85 in non survivors(0.79 - 0.94) (p=0.002). RRI values were significantly associated with ICU-death (OR =1.63-95%CI 1.06-2.49,p=0.025).A RRI cut-off value of 0.77 was identified by ROC curve. Multivariate analysis selected RRI and abdominal hypertension as strongest predictors of AKI mortality. At AKI diagnosis RRI was 0.78 (0.70 - 0.85) or 0.85 (0.73 - 0.92)(p=0.026) in patients with or without persistent AKI at discharge. Multivariate analysis selected RRI at AKI diagnosis as the strongest predictor of persistent AKI. Conclusions: High RRI values at AKI diagnosis are strictly and independently associated with in-ICU mortality and persistent AKI at ICU discharge. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · European Journal of Clinical Investigation
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    ABSTRACT: Background: A defect in gallbladder contraction function plays a key role in the pathogenesis of gallstones. The cholecystokinin-1 receptor (CCK-1R) antagonists have been extensively investigated for their therapeutic effects on gastrointestinal and metabolic diseases in animal studies and clinical trials. However, it is still unknown whether they have a potential effect on gallstone formation. Design: To study whether the CCK-1R antagonists enhances cholelithogenesis, we investigated cholesterol crystallization, gallstone formation, hepatic lipid secretion, gallbladder emptying function, and intestinal cholesterol absorption in male C57BL/6J mice treated by gavage with devazepide (4 mg/day/kg) or vehicle (as controls) twice per day and fed the lithogenic diet for 21 days. Results: During 21 days of feeding, oral administration of devazepide significantly accelerated cholesterol crystallization and crystal growth to microlithiasis, with 40% of mice forming gallstones. Whereas, only agglomerated cholesterol monohydrate crystals were found in mice receiving vehicle. Compared to the vehicle group, fasting and postprandial residual gallbladder volumes in response to the high-fat meal were significantly larger in the devazepide group during cholelithogenesis, showing reduced gallbladder emptying and bile stasis. Moreover, devazepide significantly increased hepatic secretion of biliary cholesterol, but not phospholipids or bile salts. The percentage of intestinal cholesterol absorption was higher in devazepide-treated mice, increasing bioavailability of chylomicron-derived cholesterol in the liver for biliary hypersecretion into bile. These abnormalities induced supersaturated bile and rapid cholesterol crystallization. Conclusions: The potent CCK-1R antagonist devazepide increases susceptibility to gallstone formation by impairing gallbladder emptying function, disrupting biliary cholesterol metabolism, and enhancing intestinal cholesterol absorption in mice. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · European Journal of Clinical Investigation
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    ABSTRACT: Background: Cardiovascular disease (CVD) is the worldwide leading cause of morbidity and mortality. An early risk detection of apparently healthy people before CVD onset has clinical relevance in the prevention of cardiovascular events. We evaluated the association between the product of fasting plasma glucose and triglycerides (TyG index) and CVD. Material and methods: A total of 5014 patients of the Vascular Metabolic CUN cohort (VMCUN cohort) were followed up during a median period of 10 years. We used a Cox proportional hazard ratio with repeated-measures to estimate the risk of incidence of CVD across quintiles of the TyG index, calculated as ln[fasting triglycerides (mg/dL) x fasting plasma glucose (mg(dL)/2], and plotted a receiver operating characteristics (ROC) curve to compare a prediction model fitted on the variables used in the Framingham risk score, a new model containing the Framingham variables with the TyG index, and the risk of coronary heart disease. Results: A higher level of TyG index was significantly associated with an increased risk of developing CVD independent of confounding factors with a value of 2.32 (95% CI: 1.65-3.26) for those in the highest quintile, and 1.52 (95% CI: 1.07-2.16) for those in the fourth quintile. The areas under the curve (AUC) of the ROC plots were 0.708 (0.68-0.73) for the Framingham model, 0.719 (0.70-0.74) for the Framingham + TyG index model (p=0.014). Conclusions: The TyG index, a simple measure reflecting insulin resistance, might be useful to early identify individuals at a high risk of developing a cardiovascular event. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · European Journal of Clinical Investigation
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) and asthma are both characterized by heterogeneous chronic airway inflammation and obstruction as well as oxidative stress (OS). However, it is unknown whether OS occurs in early disease and how to best assess its presence. Plasma OS markers (TBARS, PSH, taurine, GSH, ergothioneine and paraoxonase 1 activity) and lung function tests were measured in patients with mild stable asthma (n=24) and mild stable COPD (n=29) and in age and sex-matched controls. Forced Expiratory Volume in 1 sec (FEV1 ) was associated with age both in patients and control groups. By contrast, FEV1 was positively correlated with PSH only in COPD (rho=0.49, p=0.007). In multiple logistic regression analysis, lower PSH was the only OS marker independently associated with increased odds of both asthma (OR=0.32, 95% CI 0.13-0.78, p=0.01) and COPD (OR=0.50, 95% CI 0.26-0.95, p=0.03). These findings suggest that proteins SH groups are a sensitive OS marker in early COPD and asthma. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · European Journal of Clinical Investigation
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    ABSTRACT: Background: The possible role of BRAF(V) (600E) mutation in the diagnosis and prognosis of papillary thyroid carcinoma (PTC) remains controversial. A systematic review to investigate the diagnostic and prognostic role of BRAF(V) (600E) mutation in patients with PTC is urgently needed. Methods: A systematic review of relevant literatures was performed in PubMed, Embase, and CENTRAL. The incremental accuracy (IA) of fine needle aspiration biopsy plus BRAF(V) (600E) mutation analysis over fine needle aspiration biopsy alone, and the statistical data about the association of BRAF(V) (600E) mutation and the prognosis of PTC (risk ratios (RR) for dichotomous data, standard mean differences for continuous data and hazard ratios (HRs) for disease free survival (DFS)) were pooled. Subgroup analysis was performed to explain the heterogeneities. Results: A total of 67 studies were included. The pooled IA was 2% (95% confidence interval (CI): 0.5-4%). The pooled RR for gender, multifocality, lymph node metastasis, extrathyroidal invasion, and pathological stage was 1.11 (95%CI: 0.98-1.25), 1.17 (95%CI: 1.09-1.24), 1.36 (95%CI: 1.20-1.53), 1.60 (95%CI: 1.41-1.82), and 1.49 (95%CI: 1.33-1.68), respectively. The pooled standard mean differences for age and tumor size were 0.14 (95%CI: 0.04-0.23) and 0.21 (95%CI: 0.1-0.32), respectively. The pooled HR for DFS was 1.96 (95%CI: 1.62-2.37). Subgroup analysis showed that these statistical results were affected by the geographical background of patients, study design and detection methods. Conclusions: BRAF(V) (600E) mutation analysis can not only be used in the diagnosis of PTC, but also can predict its pronosis. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · European Journal of Clinical Investigation
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    ABSTRACT: Background: The long-term risk-benefit effect of occasional and regular use of low-dose aspirin (≤ 100 mg per day) in primary prevention of vascular diseases and cancers was calculated. Methods: One representative database of 1,000,000 participants from Taiwan's National Health Insurance scheme in 1997-2000 was used. The potential study subjects were those aged 30-95 years, were found not to have been prescribed aspirin before 1 January 2000, but to have first been prescribed low-dose aspirin (≤ 100 mg per day) after that date, and were followed up to 31 December 2009. Participants prescribed low-dose aspirin < 20% during the study period were considered occasional users and those prescribed ≥ 80% regular users. After the propensity-score matching, rate differences of hemorrhage, ischemia, and cancer between these users were calculated their net clinical risk. Results: 1,720 pairs were analyzed. During the study period, hemorrhage and ischemia occurred in 25 (1.45%) and 67 participants (3.90%) in occasional users and 69 (4.01%) and 100 participants (5.81%) in regular users, whereas cancer occurred in 32 participants (1.86%) in occasional users and 26 participants (1.51%) in regular users. The crude and adjusted net clinical risks of low-dose aspirin use between the two frequency of users (≥ 80% vs. < 20%) were 4.12% (95% CI = 2.19%, 6.07%; P < 0.001) and 3.93% (95% CI = 2.01%, 5.84%; P < 0.001). Conclusions: A long-term regular use of low-dose aspirin might not be better than occasional use in the primary prevention against major vascular diseases and cancer. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · European Journal of Clinical Investigation
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    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.
    No preview · Article · Nov 2015 · European Journal of Clinical Investigation
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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.
    No preview · Article · Nov 2015 · European Journal of Clinical Investigation
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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.
    No preview · Article · Nov 2015 · European Journal of Clinical Investigation
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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.
    No preview · Article · Nov 2015 · European Journal of Clinical Investigation