To improve management of patients with Graves' orbitopathy, a multi-center collaborative approach is necessary in order to have large enough sample sizes for meaningful randomized clinical trials. This is hampered by a lack of consensus on how to investigate the eye condition. The European Group on Graves' Orbitopathy aims to overcome this and has designed a preliminary case record form (CRF) to assess Graves' orbitopathy patients. This form was used in this first multi-center study. Aim: To investigate patient characteristics and treatment strategies in 152 new consecutively referred patients with thyroid eye disease seen in nine large European referral centers. Methods: Newly referred patients with Graves' orbitopathy were included who were seen between September and December 2000. Demographic data and a complete ophthalmological assessment were recorded. Results: One-hundred and fifty-two patients (77% females) were included. Diabetes was present in 9%, and glaucoma or cataract in 14% of patients. Forty percent were current smokers, 9% also had dermopathy, and only 33% reported a positive family history of thyroid disease. Mild eye disease was seen in 40%, moderately severe eye disease was seen in 33% and severe eye disease was seen in 28% of patients. Soft tissue involvement was the most frequent abnormality (seen in 75%), proptosis $ 21 mm was found in 63%, eye motility dysfunction in 49%, keratopathy in 16% and optic nerve involvement was found in 21% of patients. According to the clinical impression, 60% had active eye disease. Immunosuppressive treatment was planned more frequently in active patients (57/86; 66%) than in inactive patients (5/57, 9%; Chi-square 46.16; P , 0:02). There were no important differences among the eight centers regarding the severity and the activity of their patients. Conclusions: In view of the large number of patients recruited in only 4 months, multi-center studies in the eight EUGOGO centers appear to be feasible.

Yield and Accuracy of Diagnosing TLOC. Background: Transient loss of consciousness (TLOC) is a common clinical problem.Objective: The aim of this study was to assess the yield and accuracy of the initial evaluation, consisting of standardized history, physical examination, and ECG performed by attending physicians in patients with TLOC.Methods and Results: Five hundred and three adult patients (mean age 53 ± 19; 56% male) presenting with TLOC to the Academic Medical Center Amsterdam between February 2000 and May 2002 were included in this study. After initial evaluation, the physician made a certain, a highly likely (>80% certain), or no initial diagnosis. Initially undiagnosed patients received additional cardiological testing, additional history taking, and autonomic function tests. After 2 years of follow-up, an expert committee determined the final diagnoses.Two-year follow-up was obtained in 99% of the patients. The yield of certain diagnoses after the initial evaluation was 24%, increasing to 63% after including the highly likely diagnoses. The diagnostic accuracy of the initial certain diagnoses was 93% (95% CI 87-97%), decreasing to 88% (95% CI 84-91%) after inclusion of the initial highly likely diagnoses.Conclusion: Attending physicians can make a diagnosis based on initial evaluation in 63% of patients with TLOC, with an overall diagnostic accuracy of 88%. The use of additional testing, beyond history, physical examination, and ECG can be avoided in many patients with

BackgroundCoronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls.Methodology/Principal FindingsIn this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts.Conclusion/SignificanceTwo miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective study.

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