Martin Uffmann

Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score

IntroductionFrequent assessments of rheumatoid arthritis (RA) disease activity allow timely adaptation of therapy, which is essential in preventing disease progression. However, values of acute phase reactants (APRs) are needed to calculate current composite activity indices, such as the Disease Activity Score (DAS)28, the DAS28-CRP (i.e. the DAS28 using C-reactive protein instead of erythrocyte sedimentation rate) and the Simplified Disease Activity Index (SDAI). We hypothesized that APRs make limited contribution to the SDAI, and that an SDAI-modification eliminating APRs – termed the Clinical Disease Activity Index (CDAI; i.e. the sum of tender and swollen joint counts [28 joints] and patient and physician global assessments [in cm]) – would have comparable validity in clinical cohorts.MethodData sources comprised an observational cohort of 767 RA patients (average disease duration 8.1 ± 10.6 years), and an independent inception cohort of 106 patients (disease duration 11.5 ± 12.5 weeks) who were followed prospectively.ResultsOur clinically based hypothesis was statistically supported: APRs accounted only for 15% of the DAS28, and for 5% of the SDAI and the DAS28-CRP. In both cohorts the CDAI correlated strongly with DAS28 (R = 0.89–0.90) and comparably to the correlation of SDAI with DAS28 (R = 0.90–0.91). In additional analyses, the CDAI when compared to the SDAI and the DAS28 agreed with a weighted kappa of 0.70 and 0.79, respectively, and comparably to the agreement between DAS28 and DAS28-CRP. All three scores correlated similarly with Health Assessment Questionnaire (HAQ) scores (R = 0.45–0.47). The average changes in all scores were greater in patients with better American College of Rheumatology response (P < 0.0001, analysis of variance; discriminant validity). All scores exhibited similar correlations with radiological progression (construct validity) over 3 years (R = 0.54–0.58; P < 0.0001).ConclusionAPRs add little information on top (and independent) of the combination of clinical variables included in the SDAI. A purely clinical score is a valid measure of disease activity and will have its greatest merits in clinical practice rather than research, where APRs are usually always available. The CDAI may facilitate immediate and consistent treatment decisions and help to improve patient outcomes in the longer term.

Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis

Background: Early treatment prevents progression of joint damage in rheumatoid arthritis (RA), but diagnosis in early disease is impeded by lack of appropriate diagnostic criteria. Objective: To study the value of rheumatoid factor (RF), anti-cyclic citrullinated peptide autoantibodies (anti-CCP), and anti-RA33 autoantibodies for diagnosis of RA and prediction of outcome in patients with very early arthritis. Methods: The prospective follow up inception cohort included 200 patients with very early (<3 months) inflammatory joint disease. Autoantibodies were measured at baseline and analysed in a tree based model which aimed at determining the added diagnostic value of testing for anti-CCP and anti-RA33 as compared with RF alone. Results: RA was diagnosed in 102 patients, while 98 developed other inflammatory arthropathies. Receiver operator curve analysis showed an optimum cut off level for RF at 50 U/ml, above which anti-CCP and anti-RA33 had no additional diagnostic value. Remarkably, RF ⩾50 U/ml and anti-CCP showed similar sensitivity and high specificity for RA, but overlapped considerably. Anti-RA33 was less specific and did not correlate with RF or anti-CCP. Among patients with RA, 72% showed at least one of these three autoantibodies, compared with 15% of non-RA patients. RF ⩾50 U/ml and anti-CCP were predictors of erosive disease, whereas anti-RA33 was associated with mild disease. Conclusions: Stepwise autoantibody testing in early inflammatory joint disease, starting with RF, followed by anti-CCP (in patients with RF <50 U/ml), and finally anti-RA33, should be used as a sensitive and effective strategy for distinguishing patients with RA at high risk for poor outcome.

Clinical value of MRI liver-specific contrast agents: a tailored examination for a confident non-invasive diagnosis of focal liver lesions

Screening of the liver for hepatic lesion detection and characterization is usually performed with either ultrasound or CT. However, both techniques are suboptimal for liver lesion characterization and magnetic resonance (MR) imaging has emerged as the preferred radiological investigation. In addition to unenhanced MR imaging techniques, contrast-enhanced MR imaging can demonstrate tissue-specific physiological information, thereby facilitating liver lesion characterization. Currently, the classes of contrast agents available for MR imaging of the liver include non-tissue-specific extracellular gadolinium chelates and tissue-specific hepatobiliary or reticuloendothelial agents. In this review, we describe the MR features of the more common focal hepatic lesions, as well as appropriate imaging protocols. A special emphasis is placed on the clinical use of non-specific and liver-specific contrast agents for differentiation of focal liver lesions. This may aid in the accurate diagnostic workup of patients in order to avoid invasive procedures, such as biopsy, for lesion characterization. A diagnostic strategy that considers the clinical situation is also presented.

Response to therapy with interferon alpha-2b and prednisolone in aggressive systemic mastocytosis: report of five cases and review of the literature

Aggressive systemic mastocytosis (ASM) is a hematopoietic neoplasm characterized by infiltration of visceral organs by neoplastic mast cells (MCs) with consecutive organopathy and respective clinical and laboratory findings (so called C-Findings). Whereas, it is generally appreciated that patients with ASM are candidates for pharmacological intervention, no ideal drug or drug combination have been identified yet. One drug proposed to work in ASM is interferon alpha-2b (IFN-alpha2b). However, little is known so far about the quality of responses to IFN-alpha2b and actual response rates. We here report on five ASM patients treated with either a combination of IFN-alpha2b (3x3 million units per week) and prednisolone (n=4), or IFN-alpha2b alone (n=1). During therapy, two of the five patients showed a major response defined by complete resolution of C-Finding(s), one a partial response (partial regression of C-Findings), and one a stable disease (no changes in C-Findings). In one patient, progression to mast cell leukemia was seen after 3 months. In contrast to the other patients, this patient exhibited >10% MCs in his bone marrow (bm) smear at first presentation. In summary, our data confirm beneficial effects of IFN-alpha2b (plus prednisolone) for a group of patients with ASM, whereas patients with mast cell leukemia may require more aggressive therapy. Prospective trials with more patients are now required to further document these drug effects and to better define subgroups of patients with ASM who show good and long-lasting responses to IFN-alpha2b.

Digital radiography: The balance between image quality and required radiation dose

Although the transition from conventional screen-film imaging to digital image acquisition has been almost completed during the last couple of years, examination parameters, such as tube voltage, tube current, and filtration have been adopted from screen-film technology without further adjustments. Digital systems, however, are characterised by their flexibility: the acquisition dose can be reduced at the expense of image quality and vice versa. The imaging parameters must be optimised according to the best performance of a particular system. The traditional means of dose containment, such as positioning and collimation, are as valid for digital techniques as they were for conventional techniques. Digital techniques increasingly offer options for dose reduction. At the same time, there is a risk of substantially increasing the patient dose, possibly unawares, due to the lack of visual control. Therefore, implementation of dose indicators and dose monitoring is mandatory for digital radiography. The use of image quality classes according to the dose requirements of given clinical indications are a further step toward modern radiation protection.

Digital chest radiography: an update on modern technology, dose containment and control of image quality

The introduction of digital radiography not only has revolutionized communication between radiologists and clinicians, but also has improved image quality and allowed for further reduction of patient exposure. However, digital radiography also poses risks, such as unnoticed increases in patient dose and suboptimum image processing that may lead to suppression of diagnostic information. Advanced processing techniques, such as temporal subtraction, dual-energy subtraction and computer-aided detection (CAD) will play an increasing role in the future and are all targeted to decrease the influence of distracting anatomic background structures and to ease the detection of focal and subtle lesions. This review summarizes the most recent technical developments with regard to new detector techniques, options for dose reduction and optimized image processing. It explains the meaning of the exposure indicator or the dose reference level as tools for the radiologist to control the dose. It also provides an overview over the multitude of studies conducted in recent years to evaluate the options of these new developments to realize the principle of ALARA. The focus of the review is hereby on adult applications, the relationship between dose and image quality and the differences between the various detector systems.

Lung manifestation in asymptomatic patients with primary Sjögren syndrome : Assessment with high resolution CT and pulmonary function tests

The authors studied 37 consecutive patients with primary Sjögren syndrome and normal chest radiographs. Thin-section CT images were analyzed using a semiquantitative grading system. The presence, distribution, and severity of 9 morphologic parameters were assessed. In 34 patients, CT findings were correlated to pulmonary function tests (PFTs). Abnormal high resolution CT (HRCT) findings were seen in 24 of 37 patients (65%): interlobular septal thickening, n = 9; micronodules, n = 9; ground glass attenuation n = 4; parenchymal cysts, n = 5. Intralobular opacities, honey combing, bronchial wall thickening, bronchiectasis, and pleural irregularities were less frequent. Both HRCT and PFTs were normal in 10 patients. Computed tomography was normal in four patients with PFTs that indicated the presence of small airway disease. High resolution CT abnormalities were found in seven patients with normal PFT. The overall correlation between HRCT and PFTs was poor. High resolution CT and PFTs appear to be sensitive for both the early detection of parenchymal abnormalities and a decreases in lung function in asymptomatic patients with primary Sjögren syndrome. However, abnormal HRCT findings do not necessarily indicate a substantial alteration in PFTs.

Does marathon running cause acute lesions of the knee? Evaluation with magnetic resonance imaging

Abstract An investigation was conducted into whether running a marathon causes acute alterations in menisci, cartilage, bone marrow, ligaments, or joint effusions, which could be evaluated by magnetic resonance imaging (MRI). Twenty-two non-professional marathon runners underwent MRI of the knee before and immediately after running a marathon. Lesions of menisci and cartilage (five-point scale), bone marrow, ligaments (three-point scale), joint effusion, and additional findings were evaluated and a total score was assessed. Before the marathon, grade 1 lesions of the menisci were found in eight runners, and grade 2 lesions in five runners. After the marathon, an upgrading from a meniscal lesion grade 1 to grade 2 was observed in one runner. Before the marathon, grade 1 cartilage lesions were found in three runners, and grade 2 lesions in one runner, all of which remained unchanged after the marathon. Before and after the marathon, unchanged bone marrow edema was present in three runners and unchanged anterior cruciate ligament lesions (grade 1) were seen in two runners. Joint effusions were present in 13 runners in the pre-run scans, slightly increased in four runners after the marathon, and newly occurred in one runner after the marathon. A total score comprising all knee lesions in each runner showed an increase after the marathon in two runners, whereas no runner showed an improvement of the radiological findings (Wilcoxon signed-rank test, P>0.05). The evaluation of lesions of the knee with MRI shows that marathon running does not cause severe, acute lesions of cartilage, ligaments, or bone marrow of the knee in well-trained runners. Only subtle changes, such as joint effusions or increased intrameniscal signal alterations, were imaged after running a marathon.

Dedicated multi-detector CT of the esophagus: spectrum of diseases

Multi-detector computed tomography (CT) offers new opportunities in the imaging of the gastrointestinal tract. Its ability to cover a large volume in a very short scan time, and in a single breath hold with thin collimation and isotropic voxels, allows the imaging of the entire esophagus with high-quality multiplanar reformation and 3D reconstruction. Proper distention of the esophagus and stomach (by oral administration of effervescent granules and water) and optimally timed administration of intravenous contrast material are required to detect and characterize disease. In contrast to endoscopy and double-contrast studies of the upper GI tract, CT provides information about both the esophageal wall and the extramural extent of disease. Preoperative staging of esophageal carcinoma appears to be the main indication for MDCT. In addition, MDCT allows detection of other esophageal malignancies, such as lymphoma and benign esophageal tumors, such as leiomyma. A diagnosis of rupture or fistula of the esophagus can be firmly established using MDCT. Furthermore, miscellaneous esophageal conditions, such as achalasia, esophagitis, diverticula, and varices, are incidental findings and can also be visualized with hydro-multi-detector CT. Multi-detector CT is a valuable tool for the evaluation of esophageal wall disease and serves as an adjunct to endoscopy.

Digital radiography of the chest: detector techniques and performance parameters.

Substantial advances in detector technology characterize digital chest radiography. This article compares the various systems from a radiologists point of view. Computed radiography (CR) is a well-established system that is robust, has good reproducibility, and is relatively inexpensive. Image quality has been continuously improved in recent years while the physical size of the readout units has been reduced and the throughput increased. CR is the only digital system that can be used for bedside chest radiographs. Improved detector properties and dual reading have made it a dose-efficient system. Although now widely available, a 4K image matrix does not appear to offer a general diagnostic improvement for imaging the chest. New developments with respect to detector composition and readout process can be expected in the future. Direct radiography (DR) is the common name for different technologies that are characterized by a direct readout matrix that covers the whole exposure area. Conversion of x-ray intensity into electric signals can either be direct (selenium-based systems) or indirect (scintillator/photodiode systems). Advantages of DR systems are a high image quality and the potential for dose reduction. The role of selenium radiography (Thoravision) has decreased after the advent of DR systems although this dedicated chest unit offers high image quality at 400 speed acquisition dose. Especially in a PACS environment, CR and DR systems will increasingly substitute for conventional radiography with advantages for CR for bedside chest radiographs and for DR for high-end chest stands.