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European Journal of Clinical Investigation

Na Wu, Xinghua Chen, Mingyang Li, Xiaolong Qu, Yueli Li, Weijia Xie, Long Wu, Ying Xiang, Yafei Li, Li Zhong
BACKGROUND: Carotid ultrasound is a non-invasive tool for risk assessment of coronary artery disease (CAD). There is no consensus on which carotid ultrasound parameter constitutes the best measurement of atherosclerosis. We investigated which model of carotid ultrasound parameters and clinical risk factors (CRF) have the highest predictive value for CAD. MATERIALS AND METHODS: We enrolled 2431 consecutive patients who have suspected CAD and underwent coronary angiography and carotid ultrasound with measurements of carotid intima-media thickness (CIMT), total number of plaques and areas of different types of plaques classified by echogenicity...
May 21, 2018: European Journal of Clinical Investigation
Sophie I Mavrogeni, Flora Bacopoulou, Despoina Apostolaki, George P Chrousos
Sudden cardiac death (SCD) is the non-traumatic death, due to loss of heart function that occurs suddenly and unexpectedly within 6 hours of a previously normal state of health. It is related to intense competitive sports promoting ventricular tachycardia (VT)/ventricular fibrillation (VF) in the presence of underlying abnormal substrate. A serial evaluation of cardiac physiologic changes taking place during training will allow the better understanding of athlete's heart and will facilitate its discrimination from other gray-zone cardiomyopathies...
May 21, 2018: European Journal of Clinical Investigation
Dirk Roos, Martin de Boer
Retrotransposable elements are stretches of DNA that encode proteins with the inherent ability to insert their own RNA or another RNA by reverse transcriptase as DNA into a new genomic location. In humans, the only autonomous retrotransposable elements are members of the Long INterspersed Element-1 (LINE-1) family. LINE-1s may cause gene inactivation and human disease. We present a brief summary of the published knowledge about LINE-1s in humans and the RNAs that these elements can transpose, and we focus on the effect of LINE-1-mediated retrotransposition on human neutrophil function...
May 17, 2018: European Journal of Clinical Investigation
Nicola Tamassia, Francisco Bianchetto-Aguilera, Fabio Arruda-Silva, Elisa Gardiman, Sara Gasperini, Federica Calzetti, Marco A Cassatella
Polymorphonuclear neutrophils are the most numerous leukocytes present in human blood, and function as crucial players in innate immune responses. Neutrophils are indispensable for the defence towards microbes, as they effectively counter them by releasing toxic enzymes, by synthetizing reactive oxygen species and by producing inflammatory mediators. Interestingly, recent findings have highlighted an important role of neutrophils also as promoters of the resolution of inflammation process, indicating that their biological functions go well beyond simple pathogen killing...
May 17, 2018: European Journal of Clinical Investigation
Sahra A Belambri, Loïc Rolas, Houssam Raad, Margarita Hurtado-Nedelec, Pham My-Chan Dang, Jamel El-Benna
Neutrophils are key cells of innate immunity and during inflammation. Upon activation, they produce large amounts of superoxide anion (O2 -. ) and ensuing reactive oxygen species (ROS) to kill phagocytized microbes. The enzyme responsible for O2 -. production is called the phagocyte NADPH oxidase. This is a multicomponent enzyme system that becomes active after assembly of four cytosolic proteins (p47phox , p67phox , p40phox and Rac2) with the transmembrane proteins (p22phox and gp91phox , which form the cytochrome b558 )...
May 14, 2018: European Journal of Clinical Investigation
Edoardo Sciatti, Enrico Vizzardi, Ivano Bonadei, Davide Fabbricatore, Francesco Prati, Mattia Pagnoni, Marco Metra
BACKGROUND: Nowadays there is an increased interest in the role of aortic stiffness in the pathophysiology of heart failure (HF), since it is a major determinant of left ventricular (LV) performance. We aimed at assessing the predictive value of the aortic stiffness parameters, measured by echocardiography, in patients affected by non-ischemic dilated cardiomyopathy (DCM) regarding three end-points: death, HF rehospitalization, combined death or HF rehospitalization in a long-term follow-up...
May 13, 2018: European Journal of Clinical Investigation
Sonja Vermeren, Utsa Karmakar, Adriano G Rossi
Neutrophils are amongst the first cells to be recruited to sites of infection or trauma. Neutrophil functional responsiveness is tightly regulated by many agents including soluble mediators and immune complexes. These immune cells can generate reactive oxygen species and degranulate to release abundant cytotoxic products, making them efficient at killing invading microorganisms such as bacteria and fungi. If neutrophil function is dysregulated, however, these cells have the potential to cause unwanted host tissue damage as exemplified by pathological and chronic inflammatory conditions...
May 7, 2018: European Journal of Clinical Investigation
Katia De Filippo, Sara M Rankin
Chemokines play a critical role in orchestrating the distribution and trafficking of neutrophils in homeostasis and disease. The CXCR4/CXCL12 chemokine axis has been identified as a central regulator of these processes. In this review we focus on the role of CXCR4/CXCL12 chemokine axis in regulating neutrophil release from the bone marrow and the trafficking of senescent neutrophils back to the bone marrow for clearance under homeostasis and disease. We also discuss the role of CXCR4 in fine-tuning neutrophil responses in the context of inflammation...
May 7, 2018: European Journal of Clinical Investigation
Trisha Greenhalgh, Sally Thorne, Kirsti Malterud
Faggion's claim that narrative reviews necessarily lack a predefined methodology is incorrect; in our paper we refer to (and reference) three specific methodological approaches to narrative review. He appears to have erroneously conflated our acknowledgement that narrative reviews may sometimes be done badly with the conclusion that they cannot be done well. He offers no evidence to substantiate his assertion that reproducibility should always be privileged over clarity and comprehensiveness (though as we said in the paper, we agree it sometimes should)...
May 3, 2018: European Journal of Clinical Investigation
Clovis Mariano Faggion
Greenhalgh et al. argued that narrative reviews provide 'interpretation and critique',1 which should be seen as 'complementary' to systematic reviews. While narrative reviews can facilitate discussion of relevant topics, they should not be used to support important policy and clinical decisions that address human disease2 because they lack a pre-defined methodology. This makes reproduction of the course taken by the authors impossible, which prevents a systematic check for biases that might affect both the results and the conclusions...
May 3, 2018: European Journal of Clinical Investigation
Ralph I Horwitz, Mary E Charlson, Burton H Singer
For the past 70 years, evidence generation for patient management in clinical medicine has been dominated by Evidence Based Medicine (EBM) with its emphasis on Randomized Controlled Trials (RCTs). EBM can tell us about the benefits of treatment in the average patient but not for the patient at hand; for how to initiate treatment but not how to adjust or modify therapy after treatment has started; for treatment efficacy when compared to placebo but less often when compared to other effective treatments; when outcomes are chosen as hard endpoints, but not when the predominant concerns of patients are physical limitations or social functioning or psychological distress...
April 27, 2018: European Journal of Clinical Investigation
Chiara Pantarelli, Heidi C E Welch
Rac-GTPases and their Rac-GEF activators play important roles in the recruitment and host defense functions of neutrophils. These proteins control the activation of adhesion molecules and the cytoskeletal dynamics that enable the adhesion, migration and tissue recruitment of neutrophils. They also regulate the effector functions that allow neutrophils to kill bacterial and fungal pathogens, and to clear debris. This review focusses on the roles of Rac-GTPases and Rac-GEFs in neutrophil adhesion, migration and recruitment...
April 23, 2018: European Journal of Clinical Investigation
Chia-Yu Wang, Sin-Jin Li, Twin-Way Wu, Han-Jen Lin, Jyun-Wei Chen, Harry J Mersmann, Shih-Torng Ding, Ching-Yi Chen
BACKGROUND: Pericardial adipose tissue (PAT) volume is highly associated with the presence and severity of cardiometabolic diseases, but the underlying mechanism is unknown. We previously demonstrated that a high-fat diet (HFD) induced metabolic dysregulation, cardiac fibrosis, and accumulation of more PAT in minipigs. This study used our obese minipig model to investigate the characteristics of PAT and omental visceral fat (VAT) induced by a HFD, and the potential link between PAT and HFD-related myocardial fibrosis...
April 23, 2018: European Journal of Clinical Investigation
Scott M Grundy, Corbin Williams, Gloria L Vega
The metabolic syndrome is a constellation of risk factors including dyslipidemia, dysglycemia, hypertension, a pro-inflammatory state, and a prothrombotic state. All of these factors are accentuated by obesity. However, obesity can be defined by body mass index (BMI), percent body fat, or by body fat distribution. The latter consists of upper body fat (subcutaneous and visceral fat) and lower body fat (gluteofemoral fat). Waist circumference is a common surrogate marker for upper body fat. In this study, data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999 - 2006 was examined for associations of metabolic risk factors with percent body fat, waist circumference, and BMI...
April 23, 2018: European Journal of Clinical Investigation
Diego Gómez-Moreno, José María Adrover, Andrés Hidalgo
Vascular inflammation underlies most forms of cardiovascular disease, which remains a prevalent cause of death among the global population. Advances in the biology of neutrophils, as well as insights into their dynamics in tissues, have revealed that these cells are prominent drivers of vascular inflammation though derailed activation within blood vessels. The development of powerful imaging techniques, as well as identification of cells and molecules that regulate their activation within vessels, including platelets and catecholamines, have been instrumental to better understand the mechanisms through which neutrophils protect or damage the organism...
April 23, 2018: European Journal of Clinical Investigation
Pien Hellebrekers, Nienke Vrisekoop, Leo Koenderman
Neutrophils are one of the most important effector cells of the innate immune response(1). They are traditionally seen as a homogenous population of short lived cells mainly involved in the defense against extracellular micro-organisms by phagocytosis and intracellular killing(1,2). The cells contain a large armamentarium that aids in this function and ranges from the production of reactive oxygen species by a membrane-bound NADPH oxidase to cytotoxic proteins and peptides residing in the different granules present in the cytoplasm(3)...
April 23, 2018: European Journal of Clinical Investigation
Suzanne Schol-Gelok, Tom van der Hulle, Joseph S Biedermann, Teun van Gelder, Frederikus A Klok, Liselotte M van der Pol, Jorie Versmissen, Menno V Huisman, Marieke J H A Kruip
BACKGROUND: Acute pulmonary embolism may be ruled out by combining non-high clinical probability and a normal D-dimer level. Both antiplatelet drugs and HMG-CoA reductase inhibitors (statins) have been associated with effects on thrombus formation, potentially influencing D-dimer levels in this setting, leading to a higher rate of false-negative tests. Therefore we determined whether D-dimer levels in patients with suspected pulmonary embolism are affected by concomitant use of antiplatelet drugs and/or statins and evaluated if the effect of antiplatelet drugs or statins might affect diagnostic accuracy...
April 22, 2018: European Journal of Clinical Investigation
Chao-Wen Cheng, Che-Chang Chang, Hsiu-Wen Chen, Ching-Yu Lin, Jin-Shuen Chen
BACKGROUND: Among multiple causes, diabetic nephropathy (DN) is the major underlying renal disease that leads to end-stage renal disease (ESRD), and early diagnosis can effectively prevent or delay the progression to ESRD. Therefore, the current study aimed to develop non-invasive, accurate detection markers. MATERIALS & METHODS: For this study, 62 diabetes mellitus (DM) patients, 59 DN patients, and 21 healthy controls (HCs) were recruited. All participants' serum samples were subjected to concavanalin (Con) A affinity chromatography, which utilizes glycoproteins to discover potential markers...
April 19, 2018: European Journal of Clinical Investigation
Kyungho Lee, Jung-Ho Shin, Jeeeun Park, Subin Hwang, Hye Ryoun Jang, Wooseong Huh, Ghee Young Kwon, Yoon-Goo Kim, Ha Young Oh, Jung Eun Lee, Dae Joong Kim
BACKGROUND: IgA nephropathy (IgAN) is the most frequent primary glomerular disease and the leading cause of end-stage renal disease. We investigated clinicopathologic predictors of renal survival in patients with IgAN with a focus on glomerular filtration rate (GFR) decline slope. MATERIALS AND METHODS: We screened all patients with primary IgAN between 1995 and 2012. Renal progression was defined as doubling of serum creatinine. Using serial serum creatinine levels during the first-year, we calculated the GFR decline slopes...
April 16, 2018: European Journal of Clinical Investigation
Charlotte Rebholz, Marcin Krawczyk, Frank Lammert
Gallstone disease (GD) belongs to the most frequent disorders in gastroenterology and causes high costs in our health-care systems. Gallstones are uncommon in children but frequent in adults, in particular in women, and are mostly triggered by exogenous risk factors. However, inherited predisposition also contributes to the gallstone risk. So far several GD-predisposing gene variants have been reported, with most prominent effects being conferred by a common variant (p.D19H) of the hepatic and intestinal cholesterol transporter ABCG5/G8...
April 10, 2018: European Journal of Clinical Investigation
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