Prospective randomised comparison of diagnostic confidence and image quality with normal-dose and low-dose CT pulmonary angiography at various body weights.

OBJECTIVES To find a threshold body weight (BW) below 100 kg above which computed tomography pulmonary angiography (CTPA) using reduced radiation and a reduced contrast material (CM) dose provides significantly impaired quality and diagnostic confidence compared with standard-dose CTPA. METHODS In this prospectively randomised study of 501 patients with suspected pulmonary embolism and BW <100 kg, 246 were allocated into the low-dose group (80 kVp, 75 ml CM) and 255 into the normal-dose group (100 kVp, 100 ml CM). Contrast-to-noise ratio (CNR) in the pulmonary trunk was calculated. Two blinded chest radiologists independently evaluated subjective image quality and diagnostic confidence. Data were compared between the normal-dose and low-dose groups in five BW subgroups. RESULTS Vessel attenuation did not differ between the normal-dose and low-dose groups within each BW subgroup (P = 1.0). The CNR was higher with the normal-dose compared with the low-dose protocol (P < 0.006) in all BW subgroups except for the 90-99 kg subgroup (P = 0.812). Subjective image quality and diagnostic confidence did not differ between CT protocols in all subgroups (P between 0.960 and 1.0). CONCLUSIONS Subjective image quality and diagnostic confidence with 80 kVp CTPA is not different from normal-dose protocol in any BW group up to 100 kg. KEY POINTS • 80 kVp CTPA is safe in patients weighing <100 kg • Reduced radiation and iodine dose still provide high vessel attenuation • Image quality and diagnostic confidence with low-dose CTPA is good • Diagnostic confidence does not deteriorate in obese patients weighing <100 kg.

Tall cell papillary thyroid carcinoma: new diagnostic criteria and mutations in BRAF and TERT

The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role of a minor TC component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates: BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations. Using a novel approach, we enriched a collective with PTCs that harbored an adverse outcome, which overcame the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of which had an adverse outcome. The proportion of TCs that constituted a poor prognosis was assessed. All of the tumors underwent sequencing for TERT promoter and BRAF V600E mutational status and were stained with an antibody to detect the BRAF V600E mutation. A 10% cutoff for TCs was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that TCs above 10% were the only significant factor for overall, tumor-specific, and relapse-free survival. Seven percent of the cases had a TERT promoter mutation, whereas 61% demonstrated a BRAF mutation. The presence of TC was significantly associated with TERT promoter and BRAF mutations. TERT predicted highly significant tumor relapse (P<0.001). PTCs comprised of at least 10% TCs are associated with an adverse clinical outcome and should be reported accordingly. BRAF did not influence patient outcome. Nevertheless, a positive status should encourage the search for TCs. TERT promoter mutations are a strong predictor of tumor relapse, but their role as a surrogate marker for TCs is limited.

Index Tracking Using Data-Mining Techniques and Mixed-Binary Linear Programming

Index tracking has become one of the most common strategies in asset management. The index-tracking problem consists of constructing a portfolio that replicates the future performance of an index by including only a subset of the index constituents in the portfolio. Finding the most representative subset is challenging when the number of stocks in the index is large. We introduce a new three-stage approach that at first identifies promising subsets by employing data-mining techniques, then determines the stock weights in the subsets using mixed-binary linear programming, and finally evaluates the subsets based on cross validation. The best subset is returned as the tracking portfolio. Our approach outperforms state-of-the-art methods in terms of out-of-sample performance and running times.

Hypereosinophiliesyndrome

In den vergangenen Jahren wurden zahlreiche neue Erkenntnisse zur Biologie eosinophiler Granulozyten, ihrer Rolle für die Gesundheit und bei Krankheiten gewonnen. Differenzierte Kenntnisse zur Pathogenese, neue diagnostische Methoden und Therapeutika haben das Verständnis zur Hypereosinophilie und damit assoziierten Erkrankungen und Syndromen fundamental geändert. In dieser Übersichtsarbeit diskutieren wir die gegenwärtige Klassifikation der Hypereosinophiliesyndrome und neue Therapieansätze.

First international external quality assessment of molecular diagnostics for Mers-CoV

BACKGROUND: Since the discovery of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, diagnostic protocols were quickly published and deployed globally. OBJECTIVES: We set out to assess the quality of MERS-CoV molecular diagnostics worldwide. STUDY DESIGN: Both sensitivity and specificity were assessed using 12 samples containing different viral loads of MERS-CoV or common coronaviruses (OC43, 229E, NL63, HKU1). RESULTS: The panel was sent to more than 106 participants, of which 99 laboratories from 6 continents returned 189 panel results.Scores ranged from 100% (84 laboratories) to 33% (1 laboratory). 15% of respondents reported quantitative results, 61% semi-quantitative (Ct-values or time to positivity) and 24% reported qualitative results. The major specific technique used was real-time RT-PCR using the WHO recommended targets upE, ORF1a and ORF1b. The evaluation confirmed that RT-PCRs targeting the ORF1b are less sensitive, and therefore not advised for primary diagnostics. CONCLUSIONS: The first external quality assessment MERS-CoV panel gives a good insight in molecular diagnostic techniques and their performances for sensitive and specific detection of MERS-CoV RNA globally. Overall, all laboratories were capable of detecting MERS-CoV with some differences in sensitivity. The observation that 8% of laboratories reported false MERS-CoV positive single assay results shows room for improvement, and the importance of using confirmatory targets.

CT based volume measurement and estimation in cases of pericardial effusion

The measurement of fluid volumes in cases of pericardial effusion is a necessary procedure during autopsy. With the increased use of virtual autopsy methods in forensics, the need for a quick volume measurement method on computed tomography (CT) data arises, especially since methods such as CT angiography can potentially alter the fluid content in the pericardium. We retrospectively selected 15 cases with hemopericardium, which underwent post-mortem imaging and autopsy. Based on CT data, the pericardial blood volume was estimated using segmentation techniques and downsampling of CT datasets. Additionally, a variety of measures (distances, areas and 3D approximations of the effusion) were examined to find a quick and easy way of estimating the effusion volume. Segmentation of CT images as shown in the present study is a feasible method to measure the pericardial fluid amount accurately. Downsampling of a dataset significantly increases the speed of segmentation without losing too much accuracy. Some of the other methods examined might be used to quickly estimate the severity of the effusion volumes.

Comparison among gold standard techniques used for the validation of methods for occlusal caries detection

The aim of this in vitro study was to assess the agreement among four techniques used as gold standard for the validation of methods for occlusal caries detection. Sixty-five human permanent molars were selected and one site in each occlusal surface was chosen as the test site. The teeth were cut and prepared according to each technique: stereomicroscopy without coloring (1), dye enhancement with rhodamine B (2) and fuchsine/acetic light green (3), and semi-quantitative microradiography (4). Digital photographs from each prepared tooth were assessed by three examiners for caries extension. Weighted kappa, as well as Friedman's test with multiple comparisons, was performed to compare all techniques and verify statistical significant differences. Results: kappa values varied from 0.62 to 0.78, the latter being found by both dye enhancement methods. Friedman's test showed statistical significant difference (P < 0.001) and multiple comparison identified these differences among all techniques, except between both dye enhancement methods (rhodamine B and fuchsine/acetic light green). Cross-tabulation showed that the stereomicroscopy overscored the lesions. Both dye enhancement methods showed a good agreement, while stereomicroscopy overscored the lesions. Furthermore, the outcome of caries diagnostic tests may be influenced by the validation method applied. Dye enhancement methods seem to be reliable as gold standard methods.

Diagnostic efficacy of SonoVue, a second generation contrast agent, in the assessment of extracranial carotid or peripheral arteries using colour and spectral Doppler ultrasound: a multicentre study

The purpose of this study was to demonstrate the improvement in diagnostic quality and diagnostic accuracy of SonoVue microbubble contrast-enhanced ultrasound (CE-US) versus unenhanced ultrasound imaging during the investigation of extracranial carotid or peripheral arteries. 82 patients with suspected extracranial carotid or peripheral arterial disease received four SonoVue doses (0.3 ml, 0.6 ml, 1.2 ml and 2.4 ml) with Doppler ultrasound performed before and following each dose. Diagnostic quality of the CE-US examinations was evaluated off-site for duration of clinically useful contrast enhancement, artefact effects and percentage of examinations converted from non-diagnostic to diagnostic. Accuracy, sensitivity and specificity were assessed as agreement of CE-US diagnosis evaluated by an independent panel of experts with reference standard modality. The median duration of clinically useful signal enhancement significantly increased with increasing SonoVue doses (p< or =0.002). At the dose of 2.4 ml of SonoVue, diagnostic quality evaluated as number of inconclusive examinations significantly improved, falling from 40.7% at baseline down to 5.1%. Furthermore, SonoVue significantly (p<0.01) increased the accuracy, sensitivity and specificity of assessment of disease compared with baseline ultrasound. SonoVue increases the diagnostic quality of Doppler images and improves the accuracy of both spectral and colour Doppler examinations of extracranial carotid or peripheral arterial disease.

Percutaneous coronary interventions in Europe: prevalence, numerical estimates, and projections based on data up to 2004

AIMS: A registry mandated by the European Society of Cardiology collects data on trends in interventional cardiology within Europe. Special interest focuses on relative increases and ratios in new techniques and their distributions across Europe. We report the data through 2004 and give an overview of the development of coronary interventions since the first data collection in 1992. METHODS AND RESULTS: Questionnaires were distributed yearly to delegates of all national societies of cardiology represented in the European Society of Cardiology. The goal was to collect the case numbers of all local institutions and operators. The overall numbers of coronary angiographies increased from 1992 to 2004 from 684 000 to 2 238 000 (from 1250 to 3930 per million inhabitants). The respective numbers for percutaneous coronary interventions (PCIs) and coronary stenting procedures increased from 184 000 to 885 000 (from 335 to 1550) and from 3000 to 770 000 (from 5 to 1350), respectively. Germany was the most active country with 712 000 angiographies (8600), 249 000 angioplasties (3000), and 200 000 stenting procedures (2400) in 2004. The indication has shifted towards acute coronary syndromes, as demonstrated by rising rates of interventions for acute myocardial infarction over the last decade. The procedures are more readily performed and perceived safer, as shown by increasing rate of "ad hoc" PCIs and decreasing need for emergency coronary artery bypass grafting (CABG). In 2004, the use of drug-eluting stents continued to rise. However, an enormous variability is reported with the highest rate in Switzerland (70%). If the rate of progression remains constant until 2010 the projected number of coronary angiographies will be over three million, and the number of PCIs about 1.5 million with a stenting rate of almost 100%. CONCLUSION: Interventional cardiology in Europe is ever expanding. New coronary revascularization procedures, alternative or complementary to balloon angioplasty, have come and gone. Only stenting has stood the test of time and matured to the default technique. Facilitated access to PCI, more complete and earlier detection of coronary artery disease promise continued growth of the procedure despite the uncontested success of prevention.

Radiofrequency ablation in children and adolescents: results in 154 consecutive patients

AIMS: The experience of using radiofrequency ablation (RFA) for the treatment of arrhythmias in children and adolescents is still limited. This study aimed to review the most recent results of RF ablation in children and adolescents in a highly experienced centre with access to both conventional techniques and non-fluoroscopic electroanatomic mapping (CARTO). METHODS AND RESULTS: A total of 154 consecutive patients younger than 19 years treated with RFA during the period 2000-04 were included. Numbers (%) or median (quartiles) are reported. Age was 15 (12-17) years, 70 (45%) were males. Five patients (3%) had congenital heart disease. RFA was successful in 147/154 patients (95%). Arrhythmia recurrence occurred in 11 patients (7%). Procedure time was 55 (35-90) min and fluoroscopy time was 8.8 (4-19) min. Number of RF applications was 4 (2-10) and number of RF applications >20 s was 2 (1-7). One patient (0.7%) had complicating high-grade atrioventricular block. CARTO was used in 18 RF ablation procedures (11%) performed in 15 patients. CONCLUSION: RF ablation can be undertaken in children and adolescents with a high success rate, few recurrences and complications, very short procedure times, and acceptable fluoroscopy times. Non-fluoroscopic electroanatomic mapping is helpful in selected patients.

A review identifies and classifies reasons for ordering diagnostic tests

OBJECTIVE: To consider the reasons and context for test ordering by doctors when faced with an undiagnosed complaint in primary or secondary care. STUDY DESIGN AND SETTING: We reviewed any study of any design that discussed factors that may affect a doctor's decision to order a test. Articles were located through searches of electronic databases, authors' files on diagnostic methodology, and reference lists of relevant studies. We extracted data on: study design, type of analysis, setting, topic area, and any factors reported to influence test ordering. RESULTS: We included 37 studies. We carried out a thematic analysis to synthesize data. Five key groupings arose from this process: diagnostic factors, therapeutic and prognostic factors, patient-related factors, doctor-related factors, and policy and organization-related factors. To illustrate how the various factors identified may influence test ordering we considered the symptom low back pain and the diagnosis multiple sclerosis as examples. CONCLUSIONS: A wide variety of factors influence a doctor's decision to order a test. These are integral to understanding diagnosis in clinical practice. Traditional diagnostic accuracy studies should be supplemented with research into the broader context in which doctors perform their work.

Comparison of five diagnostic methods for detecting bovine viral diarrhea virus infection in calves

Five diagnostic techniques performed on skin biopsies (shoulder region) and/or serum were compared for detection of bovine viral diarrhea virus infection in 224 calves 0-3 months of age, 23 calves older than 3 months but younger than 7 months, and 11 cattle older than 7 months. The diagnostic methods used were immunohistochemistry (IHC), 2 commercial antigen ELISAs, 1 commercial antibody ELISA, and real-time RT-PCR. Results of 249 out of 258 skin and serum samples were identical and correlated within the 3 antigen detection methods and the real-time RT-PCR used. Twenty-six of these 249 samples were BVDV-positive with all antigen detection methods and the real-time RT-PCR. Nine out of 258 samples yielding discordant results were additionally examined by RT-PCR, RT-PCR Reamplification (ReA), and antigen ELISA I on serum and by immunohistochemistry on formalin fixed and paraffin-embedded skin biopsies. Virus isolation and genotyping was performed as well on these discordant samples. In 3 cases, transiently infected animals were identified. Two samples positive by real-time RT-PCR were interpreted as false positive and were ascribed to cross-contamination. The antigen ELISA II failed to detect 2 BVDV-positive calves due to the presence of maternal antibodies; the cause of 2 false-positive cases in this ELISA remained undetermined. Only persistently infected animals were identified in skin samples by IHC or antigen ELISA I. The 3 antigen detection methods and the real-time RT-PCR used in parallel had a high correlation rate (96.5%) and similar sensitivity and specificity values.