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: 2.83

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 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 3.05
Cited half-life 8.00
Immediacy index 0.70
Eigenfactor 0.01
Article influence 0.90
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
    • On a non-profit server
    • 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
    ​ yellow

Publications in this journal

  • M Khodaeian · O Tabatabaei-Malazy · M Qorbani · F Farzadfar · P Amini · B Larijani
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    ABSTRACT: Data regarding the effect of vitamin C (VC) and vitamin E (VE) supplementation on insulin resistance in type 2 diabetes mellitus (T2DM) are controversial. We aimed to systematically review the current data on this topic. All randomized controlled trials (RCTs) conducted to assess the effect of VC and/ or VE on insulin resistance in diabetes, published in Google Scholar, and PubMed web databases until January 2014 were included. Exclusion criteria were studies conducted in animal, Type 1 DM, children or pregnant women. Main outcome measure was insulin resistance by homeostasis model assessment (HOMA) index. According to degree of heterogeneity, fixed or random effect model were employed by STATA software (11.0). We selected 14 RCTs involving 735 T2DM patients. VE, or mixture mode supplementation did not have significant effect on HOMA with a standardized mean difference (SMD): 0.017, 95% CI: -0.376 to 0.411, (p =0.932), and SMD: -0.035, 95% CI -0.634 to 0.025, (p =0.070), respectively by random-effect model. VC supplement alone did not improve insulin resistance with a SMD: -0.150, 95% CI -0.494 to 0.194, (p = 0.391) by fixed-effect model. Meta- regression test demonstrated that HOMA index may have not been influenced by the year of publication, dosage, or duration of treatment. Sole intake of VC, VE, or their combination with other antioxidants could not improve insulin resistance in diabetics. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 08/2015; DOI:10.1111/eci.12534
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    ABSTRACT: Obesity is strongly associated with metabolic syndrome. Recent research suggests that excess adipose tissue plays an important role in development of the syndrome. On the other hand, persons with a deficiency of adipose tissue (e.g. lipodystrophy) also manifest the metabolic syndrome. In some animal models, expansion of adipose tissue pools mitigates adverse metabolic components (e.g. insulin resistance, hyperglycemia, and dyslipidemia). Hence, there are conflicting data as to whether adipose tissue worsens the metabolic syndrome or protects against it. This conflict may relate partly to locations of adipose tissue pools. For instance, lower body adipose tissue may be protective whereas upper body adipose tissue may promote the syndrome. One view holds that in either case, the accumulation of ectopic fat in muscle and liver is the driving factor underlying the syndrome. If so, there may be some link between adipose-tissue fat and ectopic fat. But the mechanisms underlying this connection are not clear. A stronger association appears to exist between excessive caloric intake and ectopic fat accumulation. Adipose tissue may act as a buffer to reduce the impact of excess energy consumption by fat storage; but once a constant weight has been achieved, it is unclear whether adipose tissue influences levels of ectopic fat. Another mechanism whereby adipose tissue could worsen the metabolic syndrome is through release of adipokines. This is an intriguing mechanism, but the impact of adipokines on metabolic syndrome risk factors is uncertain. Thus many potential connections between adipose tissue and metabolic syndrome remain to unraveled. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 08/2015; DOI:10.1111/eci.12519
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    ABSTRACT: Background Tissue Doppler Imaging (TDI) is used to improve risk stratification in patients with chronic heart failure (CHF). So far, few studies have used this method to investigate the characteristics of subjects with CHF and Cheyne-Stokes breathing (CSB). The aim of this study was therefore to evaluate whether TDI assessment may predict the presence CSB in patients with CHF.MethodsA total of 41 consecutive patients with CHF enrolled in the Daunia Heart Failure Registry underwent echocardiography assessment and nocturnal polygraphy to evaluate the presence of sleep apnea and CSB. Conventional echocardiography and TDI parameters were calculated. We have also quantified by TDI a combined index (EAS-Index) of diastolic and systolic performance: E’/(A’ x S’).ResultsSubjects with evidence of CSB (N 8) were characterized by lower values of A’ (5.03±2.64 vs 7.88±2.64 cm/sec, p<0.01). A’ and EAS-index values were related to Cheyne-Stokes episode rates (r -0.49 and 0.52, p <0.05 and <0.01 respectively), EAS-index values also with the number of episodes of central apnea (r 0.39, p <0.05). A’ values predicted the presence of CSB at poly-somnography examination with an OR OR 0.62 (95% C.I. 0.40-0.96, p<0.05) even after correction for age and gender.ConclusionsTDI values (A’) are associated with the presence of sleep apnea at nocturnal polygraphy.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 08/2015; DOI:10.1111/eci.12520
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    ABSTRACT: Background Cancer of unknown primary (CUP) possesses distinct biology and peculiar natural history, in which the roles of the Winged and Hedgehog signalling pathways are unclear.Patients and Methods We constructed tissue microarrays and studied the immunohistochemical (IHC) expression of b-catenin, Smoothened (SMO), the transcription 3factors TCF, LEF, GLI1 in 87 CUP cases for prognostic significance.ResultsA low rate of IHC expression of proteins was seen, the cut off used being any expression in > 1% of tumor cells. At univariate analysis only nuclear IHC SMO expression displayed a statistically significant association with favorable outcome (median OS of 19 months in SMO-positive vs 12 months in SMO-negative cases, p=0.01). An activated Wnt pathway, defined as IHC expression of any of nuclear b-catenin, TCF, LEF, was significantly associated with favorable PFS (median 9 vs 5 months, p=0.037) and OS (median 19 vs 13 months, p=0.04). This prognostic impact on OS was mainly driven by nuclear expression of TCF and/or LEF (p=0.03). No prognostic significance of the Hedgehog pathway activation status, defined as IHC expression of SMO or nuclear GLI1, could be established. A favorable prognostic impact of the concurrent activation of both pathways was observed. A trend for association of activated Wnt with response to chemotherapy (Responders 67% among activated Wnt cases vs 35% among non-activated Wnt cases, p=0.07) was observed in CUP adenocarcinomas.Conclusions Activation of the Wnt pathway was a positive prognostic factor in a small CUP series, possibly via enhanced chemosensitivity. Independent validation is warranted.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 08/2015; DOI:10.1111/eci.12518
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    ABSTRACT: Background Differences in lipid parameters between patients with acute coronary syndromes and patients with stable coronary artery disease (CAD) are unclear and are addressed in the present study.Methods We enrolled 582 patients with angiographically proven stable CAD (of whom 26.9% had diabetes mellitus type 2 (T2DM)) and 182 patients with acute coronary syndromes (of whom 35.8% had T2DM).ResultsWhen compared to patients with stable CAD, HDL cholesterol and apolipoprotein A1 were significantly lower in patients with acute coronary syndromes (46 ± 16 mg/dl vs. 50 ± 16 mg/dl; p <0.001 and 139 ± 30 mg/dl vs. 155 ± 31 mg/dl; p <0.001, respectively). Analysis of covariance (ANCOVA) adjusting for age, gender, smoking, BMI, statin therapy, alcohol use, hypertension and diabetic state confirmed an independent impact of the acute coronary syndrome state on HDL-cholesterol and apolipoprotein A1 (F = 24.1; p <0.001). In contrast total cholesterol, LDL cholesterol, non HDL cholesterol and apolipoprotein B did not differ significantly between acute coronary syndromes and stable CAD patients.ConclusionHDL cholesterol and apolipoprotein A1 are lower in the acute coronary syndrome state than with stable CAD.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 08/2015; DOI:10.1111/eci.12513
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    ABSTRACT: Background Vascular calcification (VC) is highly prevalent in patients with chronic kidney disease (CKD). Low magnesium levels are associated with VC and recent in vitro studies confirm a protective role of magnesium, which is mediated by its entry into the VSMCs through the Transient Receptor Potential Melastatin 7 (TRPM7) channel. The role of Angiotensin II (Ang II) on VC is still unclear. Since Ang II is able to stimulate TRPM7 activity, we hypothesize that it might prevent VC. Thus, the aim of this study was to dissect the direct effect of Ang II on VC.Materials and methodsWe worked with a model of high phosphate (HP)-induced calcification in human aortic smooth muscle cells, which resembles the CKD-related VC.ResultsAddition of Ang II to cells growing in HP decreased calcification, which was associated with the up-regulation of the osteogenic factors BMP2, Runx2/Cbfa1, Osterix and ALP. A reduction of magnesium entry into the HP-calcifying cells was found. The treatment with Ang II avoided this reduction, which was reversed by the co-treatment with the TRPM7-inhibitor 2-APB. The protective effect of Ang II was related to AT1R-induced ERK1/2 MAPKinase activation. HP-induced calcification was also associated with the upregulation of the canonical Wnt/beta-catenin pathway, while its downregulation was related to attenuation of calcification by Ang II.Conclusionas hypothesized, Ang II prevented phosphate-induced calcification in VSMCs, which appears mediated by the increase of magnesium influx and by the activation of the ERK1/2 and the inhibition of the canonical Wnt/beta-catenin signaling pathwaysThis article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 08/2015; DOI:10.1111/eci.12517
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    ABSTRACT: Arachidonic acid (AA) is metabolized by cytochrome P450 (CYP) enzymes to vasoactive metabolites (mainly epoxyeicosatrienoic acids) which are known to play a protective role against damaging processes that may occur after re-oxygenation of the graft. We aimed to investigate whether the presence of functional polymorphisms along these metabolic routes may play a role in the outcome of renal transplantation. One-hundred-and-forty Caucasian renal transplant recipients and 137 donors were included. We determined the presence of seven common functional polymorphisms in the five genes governing the CYP-mediated AA metabolic pathway (CYP2C8, CYP2C9, CYP2J2, CYP4A11 and CYP4F2). Associations with parameters and events related to graft function and survival were retrospectively investigated throughout the first year after grafting. The CYP2J2*7 allele of the donor was significantly associated with higher risk for delayed graft function [OR=4.40 (1.45-13.37), p<0.01] and lower death-censored graft survival [107.90 (84.19-131.62) vs. 176.89 (166.47-187.32) months for CYP2J2*1/*1 grafts; log-rank p=0.015]. In addition, patients whose donors carried the CYP4A11 434S variant of the F434S polymorphism displayed impaired creatinine clearance, with statistically significant differences vs. 434FF subjects throughout the whole period of study (p<0.05, p<0.01, p<0.001 and p<0.05 for one week, one month, five months and one year after grafting, respectively). Taken together, these results indicate that variability in the CYP450 genes involved in the synthesis of eicosanoids from AA may have a significant impact on graft function and survival in renal transplantation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2015; DOI:10.1111/eci.12507
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    ABSTRACT: A suboptimal ventricular-arterial (VA) interaction may have a prolonged depressing effect on the failing heart after functional reserves forced to their limits under stress conditions such as exercise. The continuation of excessive load in the post-exercise period may be more important than the load during exercise, because the sum of post-exercise periods generally exceeds exercise time itself. We sought that exercise-induced changes in post-exercise VA coupling and pulsatile efficiency in patients with heart failure (HF). Thirty consecutive HF with reduced ejection fraction (EF) and thirty age-, sex- and peak VO2 -matched subjects with preserved EF were enrolled. Pre- and post-exercise echocardiographic and tonometric measurements were taken to calculate left ventricular and arterial elastances, arterial compliance and wave reflections, and steady and pulsatile power. VA coupling significantly deteriorated in HF group (from 1.50 ± 0.47 to 2.00 ± 0.75 mmHg.mL(-1) , P<0.01), but control group maintained basal favorable coupling status after exercise (from 1.04 ± 0.29 to 1.03 ± 0.24 mmHg.mL(-1) , P=0.77). Pulsatile percentage of total power significantly increased with exercise in HF group, whereas it showed a significant decrease in control group. The change in pulsatile power fraction was correlated with the change in augmentation pressure (r=0.41, ß=3.00, P<0.01) and inversely correlated with the change in total arterial compliance (r= -0.29, ß = -8.52, P=0.02). Our data indicates that exercise-induced VA decoupling and pulsatile inefficiency extend into post-exercise phase in patients with systolic dysfunction. The exact duration of these derangements requires further studies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2015; DOI:10.1111/eci.12504
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    ABSTRACT: Erythropoietic protoporphyria and X-Linked protoporphyria are genetic abnormalities of heme synthesis that result in excess production of protoporphyrin and that manifest as severe photosensitivity. These disorders are often associated with iron deficiency anemia [IDA]. Our aim was to determine whether hepcidin is increased in EPP/XLPP patients, resulting in decreased enteral iron absorption and IDA. Eight subjects with EPP, 1 with XLPP, and 9 controls had baseline blood and urine samples collected, and thereafter were given oral ferrous sulfate [660 mg]. Post-iron blood and urine samples were collected at 2, 4, 6, and 8 hours. Blood counts, serum cytokines, ferritin, and iron studies were analyzed at baseline. Serum iron studies, serum and urine hepcidin, and erythropoietin were analyzed at baseline and subsequent time points. At baseline, EPP-XLPP subjects had lower mean blood hemoglobin (13.9/15.3 g/dL) and serum ferritin (31.6/115 ng/mL) than controls. Serum iron levels increased markedly in both cohorts. Mean serum and urine hepcidin levels were significantly lower in the EPP-XLPP group at 4 and 8 h post-iron (serum-4 h, 3.79/26.6, 8 h, 5.79/34.6 nM; urine-4 h, 0.85/2.50, 8 h, 1.44/6.63 nmol/mmol creatinine). Serum cytokines and erythropoietin were normal and not different between groups. We conclude that serum and urine hepcidin are not inappropriately increased in EPP/XLPP subjects at baseline and do not increase over time as serum iron increases after oral ferrous sulfate. Levels of serum cytokines and Epo are normal in EPP/XLPP. The molecular basis for the iron-deficient phenotype in EPP/XLPP remains unknown. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2015; DOI:10.1111/eci.12503
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    ABSTRACT: The purpose of this study was to evaluate the effects of multiple sclerosis (MS) on the risk of venous thromboembolism (VTE) development. We identified patients diagnosed with MS in Taiwan between 1998 and 2010 by using the National Health Insurance Research Database and the Catastrophic Illness Patient Database (RCIPD). Each MS patient was frequency-matched to 4 controls according to age, sex, and the year of MS registration to the RCIPD. Patients with a history of VTE and incomplete information of age and sex were excluded. All patients were followed up from the index year until VTE diagnosis, loss to follow up, or the end of 2010. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of VTE in the MS and comparison cohorts by using Cox proportional hazards regression models. We followed up 1238 MS patients and 4952 comparison patients for approximately 6437 and 27 595 person-years, respectively. After adjusting for age, sex, and comorbidities, the MS patients exhibited a 6.87-fold increased risk of VTE compared with the control patients. Women with MS were associated with an 11.1-fold increased risk of VTE development compared with the non-MS women (95% CI: 2.70-45.5). The MS patients aged < 50 years exhibited a 14.8-fold increased risk of developing VTE compared with age-matched patients in the comparison cohort (95% CI: 2.99-73.4). The risk of VTE development increased with the duration of hospitalization stay. MS patients are associated with significantly greater risk of developing VTE compared with non-MS patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2015; DOI:10.1111/eci.12502
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    ABSTRACT: In 2013 we reported in this journal the absence of a relation between plasma ferritin and adiponectin levels in patients with manifest vascular disease[1]. Since then no studies have investigated this relation in this specific and important population. Research in the general population, including some patients with vascular disease, has again proven the inverse relation between plasma ferritin and adiponectin levels and also found a relation with adipose tissue insulin resistance[2, 3]. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2015; DOI:10.1111/eci.12499
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    ABSTRACT: We read with interest the recent article entitled "Prevalence of normal TSH value among patients with autonomously functioning thyroid nodule" by Treglia et al. (1). Their meta-analysis showed approximately half of patients with autonomously functioning thyroid nodules (AFTN) demonstrated by thyroid scintigraphy to have TSH values within normal range. Herein, we report our investigation of AFTN cases with normal TSH levels treated with radioiodine therapy (RIT). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2015; DOI:10.1111/eci.12497
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    ABSTRACT: Metastatic pheochromocytomas (PCs) and paragangliomas (PGLs) are rare neuroendocrine tumors with a strong genetic background. We searched the PubMed database through February 2015 to identify studies characterizing metastatic PCs/PGLs as well as currently established and evolving therapies. Large size tumors (>5 cm), PASS score greater than 6, and Ki-67 labelling index > 3% are the most robust indices of metastatic PCs/PGLs albeit with great variability. Germline succinate dehydrogenase complex, subunit B (SDHB) mutation constitutes the main reliable molecular predictor of malignancy. Plasma and urinary methoxytyramine are the biochemical markers characterizing metastatic PCs/PGLs along with evolving molecular markers such as miRNAs and SNAIL. Conventional imaging is used for tumor localization whereas 18F-FDG-PET for staging of metastatic PCs/PGLs especially those related to SDHB gene mutations. In addition, 68Ga-DOTATATE PET/CT is emerging as a highly sensitive alternative. Surgery remains the gold standard treatment in reducing tumor bulk and/or controlling the clinical syndrome. Treatment with 131I-MIBG or radiolabeled somatostatin analogues is considered for un-resectable disease. Conventional chemotherapy is reserved for more advanced and refractory to other therapies disease although new schemes are currently evolving. Recent genetic studies have highlighted a number of pathways involved in PCs/PGLs pathogenesis directing towards the use of targeted therapies which have still to be validated in clinical practice. Metastatic PCs/PGLs remain an orphan disease that is only curable by surgery. However advances in genomic analyses have improved the pathogenesis of these tumors and may lead to effective and more personalized treatments in the near future. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2015; DOI:10.1111/eci.12495
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    ABSTRACT: We have read with great interest the article entitled Prevalence of normal TSH value among patients with autonomously functioning thyroid nodule by Treglia et al (1). Autonomously functioning thyroid nodule (AFTN) are benign monoclonal tumors characterized by their capacity to grow and produce T4 and T3 independently of TSH regulation. AFTNs account for 5-10% of palpable nodules. Based on the assumption that normal TSH concentration rules out the presence of AFTNs, clinical guidelines on the management of thyroid nodules only recommend a thyroid scan if TSH concentration is subnormal. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 07/2015; DOI:10.1111/eci.12496