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
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Our recent drug interaction trial with clopidogrel shows that morphine decreases the concentrations and pharmacodynamic effects of clopidogrel, which could lead to treatment failure in susceptible individuals. We hypothesized that the pharmacodynamic consequences of drug-drug interactions would be less between morphine and ticagrelor. Materials and methods: Twenty-four healthy subjects received a loading dose of 180mg ticagrelor together with placebo or 5mg morphine intravenously in a randomized, double-blind, placebo-controlled, cross-over trial. Pharmacokinetics were determined by liquid chromatography tandem mass spectrometry, and ticagrelor pharmacodynamic effects were measured by platelet function tests (whole blood platelet aggregation: Multiplate, platelet plug formation: PFA-100, vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay). Results: Concomitant i.v. injection of morphine slows drug resorption of ticagrelor and its active metabolite (p<0.05) by one hour and decreases plasma levels of ticagrelor and its active metabolite by 25-31% (p<0.03) and the drug exposure (area under the curve) by 22-23% (p<0.01). Importantly, however, the pharmacodynamic effects of ticagrelor on platelet aggregation in whole blood, platelet plug formation, and VASP phosphorylation are not affected by morphine. Conclusions: Morphine co-administration moderately decreases ticagrelor plasma concentrations but does not inhibit its pharmacodynamic effects in healthy volunteers within 6 hours after drug administration. Limitations of our trial include the investigation in healthy volunteers under standardized conditions, which does not necessarily reflect a realistic emergency scenario. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12550
  • Nirmal Parajuli · Lucas Valtuille · Ratnadeep Basu · Konrad S Famulski · Philip F Halloran · Consolato Sergi · Gavin Y Oudit
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    ABSTRACT: Background: The molecular and cellular determinants of ventricular tachycardia (VT) in patients with non-ischemic dilated cardiomyopathy (NIDCM) remain poorly defined. Materials and methods: We examined 20 NIDCM hearts where VT was reported in 10 cases and VT was absent in 10 cases, using a double-blinded case control study design, and assessed the molecular and cellular features of the adverse myocardial remodeling. Results: Explanted hearts from patients with VT showed greater hypertrophic changes based on cardiomyocyte cross-sectional area and expression of disease markers, and increased myocardial fibrosis which extended into the left ventricular and right ventricular outflow tract regions. The VT group also showed increased oxidative stress with reduction in reduced glutathione levels. Connexin-43 levels in the intercalated discs showed increased levels in the VT group with reduced phosphorylation. Microarray mRNA analysis of gene expression in the left ventricle (LV) free wall revealed several families of genes which were differentially upregulated or downregulated in hearts with documented VT compared to hearts without VT. Notably, we identified reduced expression of the Ca(2+) -activated K(+) channel (KCNN2) and increased expression of the transient receptor potential cation channel 7 (TRPM7) and intracellular chloride channel 3 (CLIC3). Western blot analysis on LV membrane fractions showed reduced KCNN2 and increased TRPM7 levels in hearts with VT. Conclusions: In explanted human hearts with NIDCM, VT is associated with greater hypertrophy, oxidative stress and myocardial fibrosis, differential gene expression, and altered ion channel levels indicative of a distinctive adverse myocardial remodelling process associated with clinically-significant VT. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12549
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    ABSTRACT: Objective Meta-analysis is aiming to evaluate the effects of cardiac shock wave therapy (CSWT) on patients with ischemic heart disease (ICH).Background After 10 years of study, CSWT has been broadly applied to ICH treatment, but the actual effectiveness has never been well evaluated with a meta-analysis.MethodsMEDLINE, EMBASE, Science Direct, Cochrane Controlled Trials Register database and Chinese database were searched. The randomized controlled trials, single-arm and cohort study related to in patients with ICH undergoing CSWT were included and 14 articles were finally analyzed. The data related to the study design, patient characteristics, and outcomes were extracted. All the selected data were calculated with random effects models in weighted mean differences (WMD) and heterogeneity was carefully evaluated as well.Results(i)CSWT improves the angina pectoris symptom (including the decrease of Canadian Cardiovascular Society class (CCS) [-0.86(-1.12,-0.65),P<0.00001],nitroglycerin dosage(times/weeks)[-0.71(-1.08,-0.33),P=0.0002] and a increase of Seattle Angina Questionnaire score[5.64(3.12, 8.15),P<0.0001)]); (ii) CSWT leads to a reduce in heart failure(including a reduction of New York Heart Association functional class [-0.49(-0.62,-0.37),P<0.00001],a stable rise in 6 Minute Walking distance[68.38(39.70, 97.05),P<0.00001] and a growth in left ventricular ejection fraction with echocardiography screening[6.73(4.67,8.80),P<0.00001].);(iii)CSWT improves myocardial viability within improving in Total score of perfusion imaging[-5.19 (-8.08, -2.30), P=0.0004] and Total score of metabolism imaging[-5.33(-7.77, -2.90),P<0.0001].Conclusions The meta-analysis suggests that CSWT may offer beneficial effects to ICH patients, although there was significant heterogeneity across the studies.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12546
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    ABSTRACT: Background: Even though current treatment guidelines for idiopathic membranous glomerulonephritis (iMGN) exist, many questions regarding an optimal therapy remain unanswered. Complete remission cannot be achieved in all patients; relapses occur, in some cases frequently, and side-effects from the immunosuppressive therapy are common. Therapeutic options in high-risk patients not responding to standard immunosuppressive therapies are limited. Recent research reveals that the human M-type phospholipase A2 receptor (PLA2 R) is a causative factor in iMGN that parallels clinical disease activity. However, in some patients this correlation is not evident and additional undetermined factors seem to play a role. Design: We evaluated a new rescue protocol including plasma exchanges (PE) against albumin, intravenous immunoglobulins (IVIGs) and rituximab for 10 patients with a biopsy proven diagnosis of iMGN that were therapy-resistant to all conventional regimens and had a urinary protein to creatinine ratio of more than 10,000 mg/g Crea. We compared this protocol with standard immunosuppressive protocols including monthly alternating prednisolone plus cyclophosphamide (18 patients), cyclosporine plus prednisolone (23 patients) and rituximab alone (8 patients) in a retrospective design. Results: Our rescue regimen with PE, IVIGs and rituximab achieved partial remission in 90% of patients that had been otherwise refractory to therapy. The mean time to partial remission was 2.1 months. Furthermore two anti-PLA2 R-negative patients were also treated with this rescue regimen, achieving partial remission after one month and four months CONCLUSION: A combination of PE, IVIGs and rituximab is a treatment option to consider for high-risk patients with iMGN that are refractory to conventional therapy. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12545
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    ABSTRACT: Background: Coronary microvascular dysfunction (CMD) is an important feature of hypertrophic cardiomyopathy (HCM), which contributes negatively to symptoms and long-term outcome. Previous in vivo imaging studies in HCM suggest that left ventricular outflow tract (LVOT) gradient and genetic status are important contributors to CMD. CMD may be caused by reduced capillary density. Here we investigated if a reduction in capillary density is related to genetic status or LVOT gradient severity in an in vitro study of HCM cardiac samples. Methods: Using immunofluorescence microscopy, we analysed capillaries (Cap) and cardiomyocytes (CM) in myectomy specimens from 18 HCM patients with maximum left ventricular (LV) wall thickness ≥15mm. All subjects exhibited significant LVOT obstruction, necessitating septal myectomy. In addition, control myocardium from the LV septal wall was collected at autopsy of 6 individuals that suffered a non-cardiac death. Results: CM area was higher in HCM patients compared to controls. Capillary density was significantly lower in HCM patients compared with controls (1425±262 vs 2543±509 Cap/mm(2) , P<0.001), as was the number of Cap per CM corrected for CM area (2.2±0.5 vs 4.2±0.9 Cap/CM area, P<0.001). Capillary density did not differ between genotype-negative and genotype-positive HCM patients at similar resting LVOT gradients. A significant correlation was present between resting LVOT gradient and CM area (r=0.73, P<0.001), capillary density (r=-0.74, P<0.001) and the number of Cap per CM corrected for CM area (r=-0.82, P<0.001). Conclusions: Our data indicate that LVOT gradient, rather than genetic status, is associated with reduced capillary density in HCM. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12544
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    ABSTRACT: Gastrointestinal conditions may be broadly separated into two classifications; organic and functional disease, with functional disorders accounting for the majority of patients with chronic gastrointestinal symptoms. Functional GI disorders (FGIDs) present with no obvious pathology or well accepted biochemical mechanism and, as such, treatment strategies are limited and focus on symptoms rather than cure. Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are the most widely recognised FGIDs and there is a growing body of evidence to suggest an underlying inflammatory phenotype in subsets with these conditions. Here we discuss the current knowledge of immune involvement in FGIDs, the commonalities between the different manifestations of FGIDs and propose a new hypothesis, potentially defining an underlying immunopathological basis of these conditions. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12548
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    ABSTRACT: Background: Gastric emptying (GE) is delayed in a subset of patients with inflammatory bowel disease (IBD). We have shown before that altered release of gastrointestinal hormones may contribute to GE disturbances, but overall effects of disease activity remain unclear. Thus, we aimed to evaluate GE in IBD patients during active disease and following therapy. Design: 20 healthy subjects (HC) and 26 IBD patients hospitalized because of an acute episode of their disease (Crohn's disease (CD) n=13, ulcerative colitis (UC) n=13) underwent a standardized (13) C-octanoic acid GE breath test (baseline test). Plasma glucose, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) were measured periodically throughout the test. 16 patients underwent a second GE test after 3-4 months of therapy. Results: At baseline, 9 IBD patients had pathologically delayed GE half time (T½>150min) (p=0.028 vs. HC). Moreover, T½ was significantly longer in the total group of IBD patients than in HC (129±12 min vs. 96±7, p=0.030). Postprandial GLP-1 responses were elevated in IBD (p=0.002 vs. HC) and correlated with T½ (p=0.05). Following therapy clinical activity indices and T½ were decreased in IBD (p≤0.01 vs. baseline), and T½ no longer differed from HC (p>0.5). Moreover, GLP-1 plasma levels decreased significantly (p=0.031). Conclusions: Higher disease activity in IBD is associated with prolonged GE and increased release of GLP-1. Following effective therapy, GE is accelerated and GLP-1 release decreases significantly. Thus, increased release of GLP-1 from the inflamed mucosa might contribute to GE disturbances in IBD. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12542
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    ABSTRACT: Background: Hyaluronic acid (HA), ASAT to Platelet Ratio Index (APRI), ASAT/ALAT ratio, Fibrosis 4 score (FIB4) and Fibroscan were studied as non-invasive markers of liver fibrosis (F) in chronic viral hepatitis B (CHB) and C (CHC), in an attempt to avoid the complications of liver puncture biopsy, considered the gold standard in the evaluation of F. The aim of our research was to study if HA, APRI, ASAT/ALAT ratio, FIB4 and Fibroscan are usefull non-imvasive markers in predicting severe F in Romanian patients. Patients and methods: This was a prospective multicenter transversal and observational study, which included 76 patients with CHB/CHC. The independent effect of studied markers was tested using multiple binary logistic regression. Results: In patients with CHB and CHC, the APRI cut-off value for F4 was 0.70 ng/mL (Se=77%, Sp=78%), the FIB4 cut-off value was 2.01 (Se=77%, Sp=69%) and the Fibroscan cut-off value was 13.15 (Se=92%, Sp=88%). For patients with CHB/CHC there was a significant linear positive correlation between F and HA (r=0.42, p=0.001), Fibroscan (r=0.67, p<0.001), APRI (r=0.46, p<0.001) and FIB4 (r=0.51, p<0.001). Considering age, sex and body mass index as possible confounding factors or covariates in multivariable logistic modeling, Fibroscan was the unique test able to significantly highlight the presence of F4 score in CHB/CHC patients (p=0.009) while FIB4 test seems to have a tendence to statistical significance. Conclusion: Fibroscan, APRI and FIB4 are useful non-invasive tests for the evaluation of F4 in patients with CHB and CHC. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 10/2015; DOI:10.1111/eci.12543
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    ABSTRACT: Background: The IL7RA polymorphisms have recently been associated associated with CD4+ T-cell decline in untreated HIV-infected subjects, and CD4+ T-cell recovery in patients on combination antiretroviral therapy (cART). The aim of this study was to evaluate whether IL7RA polymorphisms are associated with CD4+ T cell recovery in HIV-infected patients on long-term cART. Study design: We performed a retrospective study in 151 naïve cART patients with severe immunodeficiency (CD4+ counts ≤200 cells/mm(3) ). IL7RA polymorphisms genotyping was performed by using Sequenom's MassARRAY platform. The outcome variable was the time to achieve the first value of CD4+ count ≥500 cells/mm(3) during the follow-up. Results: Two different trends of CD4+ T cell recovery were found in Kaplan-Meier analysis. During the first 48 months, 60/151 (39.7%) of the patients reached CD4+ T cell values ≥500 cells/mm(3) , and no differences were observed between IL7RA genotypes. After the first 48 months of follow-up, 27/151 (17.8%) of the patients reached CD4+ T cell values ≥500 cells/mm(3) , with a different pattern of CD4+ recovery depending on IL7RA genotype. Patients with rs10491434 TT genotype and rs6897932 TT genotype were more likely of achieving CD4+ value ≥500 cells/mm(3) than patients with rs10491434 CT/CC genotype (adjusted hazard ratio (aHR)=3.59; p=0.005) and patients with rs6897932 CC/CT genotype (aHR=11.7; p<0.001). Conclusions: The IL7RA polymorphisms seem to be associated with CD4+ T cell recovery in HIV-infected patients who started cART with severe immunodeficiency, in the second phase of CD4+ T cell recovery after long-term cART. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 09/2015; DOI:10.1111/eci.12539
  • European Journal of Clinical Investigation 09/2015; DOI:10.1111/eci.12515
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    ABSTRACT: I read a recent article by Marik with a great interest [1]. Marik declares that he was a new clinical investigator and had been accused of self-plagiarism. In fact, self - plagiarism or duplication is classified as an unacceptable misconduct [2]. This can be seen around the world. Routinely, it is assumed that all authors and investigators have to know that they cannot recycle their results to make a new version of the old things. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 09/2015; DOI:10.1111/eci.12536
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    ABSTRACT: Bencsik et al. [1] have recently investigated the correlation between the markers of peroxynitrite–MMP signalling and hyperlipidaemia in patients with significant coronary stenosis. They provided the first demonstration that (i) serum nitrotyrosine correlates with matrix metalloproteinase (MMP)-9 activity, (ii) lipid parameters correlate with nitrotyrosine and MMP-2 activity, (iii) myocardial function correlates with creatinine, nitrotyrosine and MMP-9 activity, and (iv) creatinine correlates with nitrotyrosine and urea nitrogen with MMP-9 activity in patients with coronary artery disease. However, Bencsik et al. [1] performed gelatin zymography from serum samples to measure circulatory MMP-2 and MMP-9 activities.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 09/2015; DOI:10.1111/eci.12537
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    ABSTRACT: Background and aimsDifferent adipokines have been associated with atherosclerotic plaque rupture and cardiovascular events, such as acute ischemic stroke (AIS). However, the potential role of these molecules in post-ischemic brain injury remains largely unknown.Methods and methodsWe performed a sub-study analysis on non-obese patients with first atherothrombotic stroke (n=35) from a recently published prospective cohort. Primary end-point was to investigate the predictive value of serum leptin/adiponectin ratio on neurological recovery at 90-day after AIS. The secondary end-point was the predictive value of serum adipokine levels of clinical and radiological outcomes at a shorter follow up (at day 1 and 7 after AIS). The radiological evaluation included ischemic lesion volume and hemorrhagic transformation (HT). The clinical examination was based on National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS).ResultsAt day 1 after AIS, serum leptin and leptin/adiponectin ratio were increased and inversely correlated with both radiological and clinical parameters at all follow up time points. Once identified the best cut-off points by receiver operator curve (ROC) analysis, risk analysis showed that higher circulating leptin improved neurological recovery at day 90. In addition, leptin/adiponectin ratio maintained statistical significance after adjustment for age, gender and thrombolysis, also predicting the occurrence of HT in the first 7 days after AIS (adjusted OR 0.15 [95% CI 0.03-0.83); p=0.030]).Conclusions Higher leptin/adiponectin ratio at day 1 predicted better neurological outcomes in patients with atherothrombotic AIS and might be potentially useful as a prognostic biomarker of the disease.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 09/2015; DOI:10.1111/eci.12538
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    ABSTRACT: A recent pilot study suggested that exercise-induced myocardial ischemia may lead to a delayed release of cardiac biomarkers, so that later sampling e.g. at 4h after exercise could be used for diagnostic purpose. In an observational study we enrolled 129 consecutive patients referred for evaluation of a suspected coronary artery disease by rest/stress myocardial perfusion single-photon emission computed tomography. The treating cardiologist used all available clinical information to quantify clinical judgment regarding the presence of myocardial ischemia using a visual analogue scale twice: prior and after stress testing. BNP-levels were determined in a blinded fashion at rest, at peak stress, and 4 hours after peak stress. The presence of myocardial ischemia was adjudicated based on perfusion single-photon emission computed tomography and coronary angiography findings by an independent cardiologist. Myocardial ischemia was detected in 58 patients (45%). Patients with myocardial ischemia had significantly higher BNP-levels at all times, compared to patients without ischemia: BNP-rest (99 vs. 61pg/ml p= 0.007), BNP-stress (125 vs. 77pg/ml p= 0.02), BNP-4h (114 vs. 71pg/ml p= 0.018). Diagnostic accuracy as quantified by the area under the receiver-operating characteristics curve (AUC) was moderate for all time points (AUC 0.64-0.66). The change in BNP between rest and 4h did not provide added value, neither to the baseline BNP-level nor to clinical judgment. In contrast to our hypothesis, myocardial ischemia did not lead to a differential delayed release of BNP. Late sampling did not seem clinically useful. 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.12535
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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