Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography in the assessment of pleural abnormalities in cancer patients: A systematic review and a meta-analysis.

OBJECTIVE: To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the assessment of pleural abnormalities in cancer patients. METHODS: A comprehensive literature search of studies published through June 2013 regarding the role of (18)F-FDG-PET and PET/CT in evaluating pleural abnormalities in cancer patients was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odd ratio (DOR) of (18)F-FDG-PET or PET/CT on a per patient-based analysis were calculated. The area under the summary ROC curve (AUC) was calculated to measure the accuracy of these methods in the assessment of pleural abnormalities. Sub-analyses considering (18)F-FDG-PET/CT and patients with lung cancer only were carried out. RESULTS: Eight studies comprising 360 cancer patients (323 with lung cancer) were included. The meta-analysis of these selected studies provided the following results: sensitivity 86% [95% confidence interval (95%CI): 80-91%], specificity 80% [95%CI: 73-85%], LR+ 3.7 [95%CI: 2.8-4.9], LR- 0.18 [95%CI: 0.09-0.34], DOR 27 [95%CI: 13-56]. The AUC was 0.907. No significant improvement considering PET/CT studies only and patients with lung cancer was found. CONCLUSIONS: (18)F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of pleural abnormalities in cancer patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. The literature focusing on the use of (18)F-FDG-PET and PET/CT in this setting remains still limited and prospective studies are needed.

MP2RAGE Multiple Sclerosis Magnetic Resonance Imaging at 3 T.

OBJECTIVES: Lesion detection and characterization in multiple sclerosis (MS) are an essential part of its clinical diagnosis and an important research field. In this pilot study, we applied the recently introduced two inversion-contrast magnetization-prepared rapid gradient echo sequence (MP2RAGE) to patients with early-stage MS.¦MATERIALS AND METHODS: The MP2RAGE is a 3-dimensional (3D) magnetization-prepared rapid gradient echo derivative providing homogeneous T1 weighting and simultaneous T1 mapping. The MP2RAGE performance was compared with that of 2 clinical routine sequences (2D fluid-attenuated inversion recovery [FLAIR] and 3D magnetization-prepared rapid gradient echo [MP-RAGE]) and 2 state-of-the art clinical research sequences (the 3D FLAIR-SPACE [sampling perfection with application-optimized contrasts by using different flip-angle evolutions], a fluid-attenuated variable flip-angle fast spin echo technique, and the 3D double-inversion recovery SPACE). A cohort of 10 early-stage female MS patients (age, 31.6 ± 4.7 years; disease duration, 3.8 ± 1.9 years; median expanded disability status scale score, 1.75) and 10 age- and gender-matched controls were enrolled after approval of the local institutional review board was obtained. Multiple sclerosis lesions were identified and assigned to brain locations and tissue types by two experienced physicians in all 5 contrasts. Subsequently, lesions were manually delineated for comparison and statistical analysis of lesion count, volume and quantitative measures.¦RESULTS AND CONCLUSIONS: The results show that the 3D T1-weighted high-resolution MP2RAGE contrast provides a sensitive means for MS lesion assessment. The additional quantitative T1 relaxation time maps obtained with the MP2RAGE provide further potential diagnostic and prognostic information that could help (a) to better discriminate lesion subtypes and (b) to stage and predict the activity and the evolution of MS. Results also indicate that the T2-weighted double-inversion recovery and FLAIR-SPACE contrasts are attractive complements to the MP2RAGE for lesion detection.

Does introduction of thresholds in decision aids benefit the patient?: Comparison between findings-based and threshold-based diagnostic decision aids.

PURPOSE: To assess how different diagnostic decision aids perform in terms of sensitivity, specificity, and harm. METHODS: Four diagnostic decision aids were compared, as applied to a simulated patient population: a findings-based algorithm following a linear or branched pathway, a serial threshold-based strategy, and a parallel threshold-based strategy. Headache in immune-compromised HIV patients in a developing country was used as an example. Diagnoses included cryptococcal meningitis, cerebral toxoplasmosis, tuberculous meningitis, bacterial meningitis, and malaria. Data were derived from literature and expert opinion. Diagnostic strategies' validity was assessed in terms of sensitivity, specificity, and harm related to mortality and morbidity. Sensitivity analyses and Monte Carlo simulation were performed. RESULTS: The parallel threshold-based approach led to a sensitivity of 92% and a specificity of 65%. Sensitivities of the serial threshold-based approach and the branched and linear algorithms were 47%, 47%, and 74%, respectively, and the specificities were 85%, 95%, and 96%. The parallel threshold-based approach resulted in the least harm, with the serial threshold-based approach, the branched algorithm, and the linear algorithm being associated with 1.56-, 1.44-, and 1.17-times higher harm, respectively. Findings were corroborated by sensitivity and Monte Carlo analyses. CONCLUSION: A threshold-based diagnostic approach is designed to find the optimal trade-off that minimizes expected harm, enhancing sensitivity and lowering specificity when appropriate, as in the given example of a symptom pointing to several life-threatening diseases. Findings-based algorithms, in contrast, solely consider clinical observations. A parallel workup, as opposed to a serial workup, additionally allows for all potential diseases to be reviewed, further reducing false negatives. The parallel threshold-based approach might, however, not be as good in other disease settings.

The influence of the symmetry energy on the giant monopole resonance of neutron-rich nuclei analyzed in Thomas-Fermi theory

We analyze the influence of the density dependence of the symmetry energy on the average excitation energy of the isoscalar giant monopole resonance (GMR) in stable and exotic neutron-rich nuclei by applying the relativistic extended Thomas-Fermi method in scaling and constrained calculations. For the effective nuclear interaction, we employ the relativistic mean field model supplemented by an isoscalar-isovector meson coupling that allows one to modify the density dependence of the symmetry energy without compromising the success of the model for binding energies and charge radii. The semiclassical estimates of the average energy of the GMR are known to be in good agreement with the results obtained in full RPA calculations. The present analysis is performed along the Pb and Zr isotopic chains. In the scaling calculations, the excitation energy is larger when the symmetry energy is softer. The same happens in the constrained calculations for nuclei with small and moderate neutron excess. However, for nuclei of large isospin the constrained excitation energy becomes smaller in models having a soft symmetry energy. This effect is mainly due to the presence of loosely-bound outer neutrons in these isotopes. A sharp increase of the estimated width of the resonance is found in largely neutron-rich isotopes, even for heavy nuclei, which is enhanced when the symmetry energy of the model is soft. The results indicate that at large neutron numbers the structure of the low-energy region of the GMR strength distribution changes considerably with the density dependence of the nuclear symmetry energy, which may be worthy of further characterization in RPA calculations of the response function.

Nuclear and cytoplasmic triiodothyronine-binding sites in primary sensory neurons and Schwann cells: radioautographic study during development.

The effects of the thyroid hormones on target cells are mediated through nuclear T3 receptors. In the peripheral nervous system, nuclear T3 receptors were previously detected with the monoclonal antibody 2B3 mAb in all the primary sensory neurons throughout neuronal life and in peripheral glia at the perinatal period only (Eur. J. Neurosci. 5, 319, 1993). To determine whether these nuclear T3 receptors correspond to functional ones able to bind T3, cryostat sections and in vitro cell cultures of dorsal root ganglion (DRG) or sciatic nerve were incubated with 0.1 nM [125I]-labeled T3, either alone to visualize the total T3-binding sites or added with a 10(3) fold excess of unlabeled T3 to estimate the part due to the non-specific T3-binding. After glutaraldehyde fixation, radioautography showed that the specific T3-binding sites were largely prevalent. The T3-binding capacity of peripheral glia in DRG and sciatic nerve was restricted to the perinatal period in vivo and to Schwann cells cultured in vitro. In all the primary sensory neurons, specific T3-binding sites were disclosed in foetal as well as adult rats. The detection of the T3-binding sites in the nucleus indicated that the nuclear T3 receptors are functional. Moreover the concomitant presence of both T3-binding sites and T3 receptors alpha isoforms in the perikaryon of DRG neurons infers that: 1) [125I]-labeled T3 can be retained on the T3-binding 'E' domain of nascent alpha 1 isoform molecules newly-synthesized on the perikaryal ribosomes; 2) the alpha isoforms translocated to the nucleus are modified by posttranslational changes and finally recognized by 2B3 mAb as nuclear T3 receptor. In conclusion, the radioautographic visualization of the T3-binding sites in peripheral neurons and glia confirms that the nuclear T3 receptors are functional and contributes to clarify the discordant intracellular localization provided by the immunocytochemical detection of nuclear T3 receptors and T3 receptor alpha isoforms.

Les pneumopathies interstitielles diffuses chroniques: un mariage de raison entre pathologiste, clinicien et radiologue [Diffuse parenchymal lung disease, multidisciplinary approach and role of pathology]

The diagnostic approach to diffuse parenchymal lung disease (DPLD) and especially to the idiopathic interstitial pneumonias has changed over the last two decades, mostly thanks to the development of high resolution CT. Though far from replacing pathology, this additional tool has contributed to the definition of new and more precise diagnostic criteria especially for idiopathic interstitial pneumonias, integrating data provided by the three main contributors: lung specialist, radiologist and pathologist. The purpose of this article is to review the role of histopathology in the multidisciplinary approach of the diagnosis of DPLD and idiopathic interstitial pneumonias.

Stochastic resonance in nonpotential systems

We propose a method to analytically show the possibility for the appearance of a maximum in the signal-to-noise ratio in nonpotential systems. We apply our results to the FitzHugh-Nagumo model under a periodic external forcing, showing that the model exhibits stochastic resonance. The procedure that we follow is based on the reduction to a one-dimensional dynamics in the adiabatic limit and in the topology of the phase space of the systems under study. Its application to other nonpotential systems is also discussed.

Scaffold attachment factor B1 directly interacts with nuclear receptors in living cells and represses transcriptional activity.

Transcriptional activity relies on coregulators that modify the chromatin structure and serve as bridging factors between transcription factors and the basal transcription machinery. Using the DE domain of human peroxisome proliferator-activated receptor gamma (PPARgamma) as bait in a yeast two-hybrid screen of a human adipose tissue library, we isolated the scaffold attachment factor B1 (SAFB1/HET/HAP), which was previously shown to be a corepressor of estrogen receptor alpha. We show here that SAFB1 has a very broad tissue expression profile in human and is also expressed all along mouse embryogenesis. SAFB1 interacts in pull-down assays not only with PPARgamma but also with all nuclear receptors tested so far, albeit with different affinities. The association of SAFB1 and PPARgamma in vivo is further demonstrated by fluorescence resonance energy transfer (FRET) experiments in living cells. We finally show that SAFB1 is a rather general corepressor for nuclear receptors. Its change in expression during the early phases of adipocyte and enterocyte differentiation suggests that SAFB1 potentially influences cell proliferation and differentiation decisions.

Simpson-Golabi-Behmel syndrome type 1 in a 27-week macrosomic preterm newborn: the diagnostic value of rib malformations and index nail and finger hypoplasia.

The Simpson-Golabi-Behmel syndrome type 1 (SGBS1, OMIM #312870) is an X-linked overgrowth condition comprising abnormal facial appearance, supernumerary nipples, congenital heart defects, polydactyly, fingernail hypoplasia, increased risk of neonatal death and of neoplasia. It is caused by mutation/deletion of the GPC3 gene. We describe a macrosomic 27-week preterm newborn with SGBS1 who presents a novel GPC3 mutation and emphasize the phenotypic aspects which allow a correct diagnosis neonatally in particular the rib malformations, hypoplasia of index finger and of the same fingernail, and 2nd-3rd finger syndactyly.

Le cancer est-il une maladie nouvelle? A propos du diagnostic des maladies tumorales dans le De Medicina de Celse [Is cancer a new disease? Apropos of diagnosis of tumor diseases in De Medicina by Celsus]

Cancer is a particularly common disease in modern societies. Moreover, epidemiology considers it typical of contemporary pathology. Nevertheless, the abundant ancient literature-in the De Medicina by Celsus, among others-leads us to believe that numerous benign and malignant tumours were observed if not identified as such. Hence, it is possible that both the change in medical conceptualization and the real increase in the prevalence are responsible for the actual importance of cancer

Progression of human carotid and femoral atherosclerosis: a prospective follow-up study by magnetic resonance vessel wall imaging.

AIMS: The time course of atherosclerosis burden in distinct vascular territories remains poorly understood. We longitudinally evaluated the natural history of atherosclerotic progression in two different arterial territories using high spatial resolution magnetic resonance imaging (HR-MRI), a powerful, safe, and non-invasive tool. METHODS AND RESULTS: We prospectively studied a cohort of 30 patients (mean age 68.3, n = 9 females) with high Framingham general cardiovascular disease 10-year risk score (29.5%) and standard medical therapy with mild-to-moderate atherosclerosis intra-individually at the level of both carotid and femoral arteries. A total of 178 HR-MRI studies of carotid and femoral arteries performed at baseline and at 1- and 2-year follow-up were evaluated in consensus reading by two experienced readers for lumen area (LA), total vessel area (TVA), vessel wall area (VWA = TVA - LA), and normalized wall area index (NWI = VWA/TVA). At the carotid level, LA decreased (-3.19%/year, P = 0.018), VWA increased (+3.83%/year, P = 0.019), and TVA remained unchanged. At the femoral level, LA remained unchanged, VWA and TVA increased (+5.23%/year and +3.11%/year, both P < 0.01), and NWI increased for both carotid and femoral arteries (+2.28%/year, P = 0.01, and +1.8%/year, P = 0.033). CONCLUSION: The atherosclerotic burden increased significantly in both carotid and femoral arteries. However, carotid plaque progression was associated with negative remodelling, whereas the increase in femoral plaque burden was compensated by positive remodelling. This finding could be related to anatomic and flow differences and/or to the distinct degree of obstruction in the two arterial territories.

Extremity exposure in nuclear medicine therapy with 90Y-labelled substances - Results of the ORAMED project

90Y-labelled radiopharmaceuticals offer promising prospects for radionuclide therapies of tumours, e.g. radioimmunotherapies (RIT), (EANM, 2007), peptide receptor radiotherapies (PRRT), (Otte et al., 1998), and selective internal radiotherapies (SIRT), (Salem and Thurston, 2006). 90Y, an almost pure high-energy beta radiation emitter (Eβ,max = 2.28 MeV), is a favourable radionuclide for therapeutic purposes. However, when preparing and performing these therapies, high activities of 90Y (>1 GBq) are to be manipulated and technicians, physicians and nurses may receive high skin exposures to the hands. If radiation protection standards are low, the exposure of staff can exceed the annual skin dose limit of 500 mSv. Within a particular work package (WP4) of the ORAMED project, comprehensive measurements in nuclear medicine departments of several hospitals in 6 European countries were carried out. The study focussed on 90Y-labelled substances such as Zevalin® and DOTATOC to achieve a representative database on staff exposure. This paper summarises the most important results and conclusions for individual monitoring of skin exposure of staff.

Necrotizing fasciitis: contribution and limitations of diagnostic imaging.

Necrotizing fasciitis is a rare, rapidly spreading, deep-seated infection causing thrombosis of the blood vessels located in the fascia. Necrotizing fasciitis is a surgical emergency. The diagnosis typically relies on clinical findings of severe sepsis and intense pain, although subacute forms may be difficult to recognize. Imaging studies can help to differentiate necrotizing fasciitis from infections located more superficially (dermohypodermitis). The presence of gas within the necrotized fasciae is characteristic but may be lacking. The main finding is thickening of the deep fasciae due to fluid accumulation and reactive hyperemia, which can be visualized using computed tomography and, above all, magnetic resonance imaging (high signal on contrast-enhanced T1 images and T2 images, best seen with fat saturation). These findings lack specificity, as they can be seen in non-necrotizing fasciitis and even in non-inflammatory conditions. Signs that support a diagnosis of necrotizing fasciitis include extensive involvement of the deep intermuscular fascias (high sensitivity but low specificity), thickening to more than 3mm, and partial or complete absence on post-gadolinium images of signal enhancement of the thickened fasciae (fairly high sensitivity and specificity). Ultrasonography is not recommended in adults, as the infiltration of the hypodermis blocks ultrasound transmission. Thus, imaging studies in patients with necrotizing fasciitis may be challenging to interpret. Although imaging may help to confirm deep tissue involvement and to evaluate lesion spread, it should never delay emergency surgical treatment in patients with established necrotizing fasciitis.