Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) characterized by clonal erythrocytosis and thrombocytosis, respectively. The main goal of therapy in ...PV and ET is to prevent thrombohemorrhagic complications. Despite a debated notion that red blood cells (RBCs) play a passive and minor role in thrombosis, there has been increasing evidence over the past decades that RBCs may play a biological and clinical role in PV and ET pathophysiology. This review summarizes the main mechanisms that suggest the involvement of PV and ET RBCs in thrombosis, including quantitative and qualitative RBC abnormalities reported in these pathologies. Among these abnormalities, we discuss increased RBC counts and hematocrit, that modulate blood rheology by increasing viscosity, as well as qualitative changes, such as deformability, aggregation, expression of adhesion proteins and phosphatidylserine and release of extracellular microvesicles. While the direct relationship between a high red cell count and thrombosis is well-known, the intrinsic defects of RBCs from PV and ET patients are new contributors that need to be investigated in depth in order to elucidate their role and pave the way for new therapeutical strategies.
In the bone marrow (BM) of adult mammals, haematopoietic stem cells (HSCs) are retained in micro-anatomical structures by adhesion molecules that regulate HSC quiescence, proliferation and ...commitment. During decades, researchers have used engraftment to study the function of adhesion molecules in HSC's homeostasis regulation. Since the 90's, progress in genetically engineered mouse models has allowed a better understanding of adhesion molecules involved in HSCs regulation by BM niches and raised questions about the role of adhesion mechanisms in conferring drug resistance to cancer cells nested in the BM. This has been especially studied in acute myeloid leukaemia (AML) which was the first disease in which the concept of cancer stem cell (CSC) or leukemic stem cells (LSCs) was demonstrated. In AML, it has been proposed that LSCs propagate the disease and are able to replenish the leukemic bulk after complete remission suggesting that LSC may be endowed with drug resistance properties. However, whether such properties are due to extrinsic or intrinsic molecular mechanisms, fully or partially supported by molecular crosstalk between LSCs and surrounding BM micro-environment is still matter of debate. In this review, we focus on adhesion molecules that have been involved in HSCs or LSCs anchoring to BM niches and discuss if inhibition of such mechanism may represent new therapeutic avenues to eradicate LSCs.
The contribution of artificial intelligence (AI) to medical imaging is currently the object of widespread experimentation. The development of deep learning (DL) methods, particularly convolution ...neural networks (CNNs), has led to performance gains often superior to those achieved by conventional methods such as machine learning. Radiomics is an approach aimed at extracting quantitative data not accessible to the human eye from images expressing a disease. The data subsequently feed machine learning models and produce diagnostic or prognostic probabilities. As for the multiple applications of AI methods in thoracic imaging, they are undergoing evaluation. Chest radiography is a practically ideal field for the development of DL algorithms able to automatically interpret X-rays. Current algorithms can detect up to 14 different abnormalities present either in isolation or in combination. Chest CT is another area offering numerous AI applications. Various algorithms have been specifically formed and validated for the detection and characterization of pulmonary nodules and pulmonary embolism, as well as segmentation and quantitative analysis of the extent of diffuse lung diseases (emphysema, infectious pneumonias, interstitial lung disease). In addition, the analysis of medical images can be associated with clinical, biological, and functional data (multi-omics analysis), the objective being to construct predictive approaches regarding disease prognosis and response to treatment.
An increasing number of newly developed drugs show bioavailability problems due to poor water solubility. Formulating the drugs as nanosuspensions may help to overcome these problems by increasing ...saturation solubility and dissolution velocity. In the present study the bioavailability of the poorly soluble fenofibrate following oral administration was investigated in rats. Four formulations were tested: a nanosuspension type DissoCube®, one solid lipid nanoparticle (SLN) preparation and two suspensions of micronized fenofibrate as reference formulations, one suspension in sirupus simplex and a second in a solution of hydroxyethy-cellulose in physiological saline. Both colloidal drug delivery systems showed approximately two-fold bioavailability enhancements in terms of rate and extent compared to the reference formulations. No significant differences were found in AUC
0–22 h as well as in
C
max and
t
max between the two colloidal delivery systems. In conclusion, nanosuspensions may be a suitable delivery system to improve the bioavailability of drugs with low water solubility.
In the framework of computer-aided diagnosis, this paper proposes a novel functionality for the computerized tomography (CT)-based investigation of the pulmonary airways. It relies on an energy-based ...three-dimensional (3-D) reconstruction of the bronchial tree from multislice CT acquisitions, up to the sixth- to seventh-order subdivisions. Global and local analysis of the reconstructed airways is possible by means of specific visualization modalities, respectively, the CT bronchography and the virtual bronchoscopy. The originality of the 3-D reconstruction approach consists in combining axial and radial propagation potentials to control the growth of a subset of low-order airways extracted from the CT volume by means of a robust mathematical morphology operator-the selective marking and depth constrained (SMDC) connection cost. The proposed approach proved to be robust with respect to a large spectrum of airway pathologies, including even severe stenosis (bronchial lumen obstruction/collapse). Validated by expert radiologists, examples of airway 3-D reconstructions are presented and discussed for both normal and pathological cases. They highlight the interest in considering CT bronchography and virtual bronchoscopy as complementary tools for clinical diagnosis and follow-up of airway diseases.
Objective: To compare the computed tomographic (CT) analysis of the distribution of gas and tissue in the lungs of patients with ARDS with that in healthy volunteers. Design: Prospective study over a ...53-month period.¶Setting: Fourteen-bed surgical intensive care unit of a university hospital. Patients and participants: Seventy-one consecutive patients with early ARDS and 11 healthy volunteers. Measurements and results: A lung CT was performed at end-expiration in patients with ARDS (at zero PEEP) and healthy volunteers. In patients with ARDS, end-expiratory lung volume (gas + tissue) and functional residual capacity (FRC) were reduced by 17 % and 58 % respectively, and an excess lung tissue of 701 ± 321 ml was observed. The loss of gas was more pronounced in the lower than in the upper lobes. The lower lobes of 27 % of the patients were characterized by "compression atelectasis," defined as a massive loss of aeration with no concomitant excess in lung tissue, and "inflammatory atelectasis," defined as a massive loss of aeration associated with an excess lung tissue, was observed in 73 % of the patients. Three groups of patients were differentiated according to the appearance of their CT: 23 % had diffuse attenuations evenly distributed in the two lungs, 36 % had lobar attenuations predominating in the lower lobes, and 41 % had patchy attenuations unevenly distributed in the two lungs. The three groups were similar regarding excess lung tissue in the upper and lower lobes and reduction in FRC in the lower lobes. In contrast, the FRC of the upper lobes was markedly lower in patients with diffuse or patchy attenuations than in healthy volunteers or patients with lobar attenuations. Conclusions: These results demonstrate that striking differences in lung morphology, corresponding to different distributions of gas within the lungs, are observed in patients whose respiratory condition fulfills the definition criteria of ARDS.PUBLICATION ABSTRACT
In this study hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) were used as polymeric carriers to improve controlled release performances of matrix tablets containing a ...soluble drug. The drug release behaviour of the systems containing these two polymers mixture and each material separately was investigated. To evaluate the effect of the dissolution medium pH, on the drug release performance, release tests were conducted at pH 1, 4.5 and 6.8. In vitro release studies demonstrated that the mixture of the two cellulose derivatives enables a better control of the drug release profiles at pH 4.5 and at 6.8 both in term of rate and mechanism. Texture analysis on the swollen tablets helps to understand drug release kinetic and mechanism. In fact, the results obtained confirm that a gel, which is characterized by high strength and consistence is less susceptible to erosion and chains disentanglement and the drug release mechanism is mainly governed by diffusion. On the contrary, gels, which show a low strength and texture, have low resistance to the fluid erosion action and the release of the active molecule is manly due to polymer relaxation and chains disentanglement moving the drug delivery kinetic towards an erosion/relaxation mechanism.
An overview of radiation hard planar and 3D pixel sensor technologies currently under development for ATLAS upgrades is presented. T*he first upgrade will be the installation in 2013 of an additional ...pixel layer inside the current Detector, the Insertable B Layer (IBL). The two technologies are competing to equip the IBL. The IBL sensor qualification procedure is described. Beam test results of un-irradiated and irradiated planar and 3D sensors are presented.
Abstract Background Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) enables the estimation of myocardial infarct (MI) extent. Nevertheless, manual quantification is time ...consuming and subjective. We sought to assess MI volume with different quantitative methods in both acute (AMI) and chronic MI (CMI). Methods CMR was performed 50 ± 21 h after MI in 52 patients and was repeated 100 ± 21 days later in a subgroup of 34 patients. Then, necrosis volumes were quantified using: 1) manual delineation, 2) automated fuzzy c-means method, and 3) + 2 to 6SD thresholding approaches. Results were compared against peak values of serum Troponin I (TnI), creatine kinase (CK) and left ventricular (LV) functional parameters: LV ejection fraction (LVEF), indexed end-diastolic (EDVi), end-systolic volumes (ESVi) and the number of hypokinetic segments (NbHk). Results For CMI, quantitative evaluation of infarct size using manual, + 2SD, + 3SD and fuzzy c-means provided equivalent results in terms of correlation coefficients for comparisons of MI volumes against LV function parameters (LVEF: r > 0.79, p < 0.0001; ESVi: r > 0.82, p < 0.0001, EDVi: r > 0.67, p < 0.0001, NbHk: r > 0.54, p < 0.0009). For AMI, + 2SD and fuzzy c-means approaches provided higher correlations for comparisons of AMI volumes against biochemical markers (CK: r > 0.79, p < 0.0001,TnI: r > 0.77, p < 0.0001) and chronic LV function parameters (LVEF: r > 0.82, p < 0.0001, NbHk: r > 0.59, p < 0.0002). Conclusions The fuzzy c-means and 2SD methods provided highest correlations with biochemical MI quantification as well as LV function parameters. The fuzzy c-means approach which does not require an arbitrary identification of the remote myocardium is fast and reproducible. It may be clinically useful in the evaluation of patients with MI.
Objectives: (a) To assess whether differences in lung morphology observed in patients with adult respiratory distress syndrome (ARDS) are associated with differences in cardiorespiratory parameters, ...lung mechanics, and outcome. (b) To propose a new ARDS Severity Score to identify patients with a high mortality risk. Design: Prospective study over a 53-month period. Setting: Fourteen-bed surgical intensive care unit of a university hospital. Patients and participants: Seventy-one consecutive patients with early ARDS. Measurements and results: Cardiorespiratory parameters were measured using a Swan-Ganz catheter, the pressure-volume (PV) curve was measured using the gross syringe method, and fast spiral computed tomography (CT) was performed. Patients with diffuse attenuations (n = 16) differed from patients with lobar attenuations (n = 26) regarding: (a) mortality rate (75 % vs. 42 %, p = 0.05), (b) incidence of primary ARDS (82 % vs. 50 %, p = 0.03), (c) respiratory compliance (47 ± 12 vs. 64 ± 16 ml per cmH2O^sup -1^ p = 0.04), and (d) lower inflexion point (8.4 ± 2.0 vs. 4.6 ± 2.0 cmH2O, p = 0.001). A third group of patients with patchy attenuations (n = 29) had a mortality rate of 41 %, a respiratory compliance of 56 ± 18 ml per cmH2O^sup -1^ and a lower inflexion point of 6.3 ± 2.7 cmH2O. The bedside chest radiograph accurately assessed lung morphology in only 42 % of the patients. In contrast to the scores based on the bedside chest radiograph, a new ARDS Severity Score based on CT lung morphology and cardiorespiratory parameters identified a subgroup of patients with a high mortality rate (≥ 60 %). Conclusions: In patients with ARDS, differences in lung morphology are associated with differences in outcome and lung mechanics. A new ARDS Severity Score based on CT lung morphology and cardiorespiratory parameters accurately identified patients with the most severe forms of ARDS and a mortality rate above 60 %.PUBLICATION ABSTRACT
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