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Endometrial carcinomas (ECs) exhibit well-recognized characteristics on MRI sequences. In T2-weighted imaging (T2WI), the tumor presents as a diffuse or well-delineated soft tissue mass with an epicenter in the endometrial cavity and a heterogeneous intermediate signal relative to the hyperintense normal endometrium and hypointense myometrium. In diffusion-weighted imaging (DWI), tumors are hyperintense at a high b value in correspondence with the hypointense signal in the apparent diffusion coefficient (ADC) map. In dynamic contrast-enhanced MRI (DCE-MRI), endometrial tumors can show slower enhancement than the myometrium in the early phases and a hypointense signal in the later phases. In summary, dynamic sequences assist in the evaluation of continuous enhancement of the subendometrial zone (best evaluated approximately 35–40 seconds after the injection of gadolinium) and the estimated degree of myometrial invasion (best evaluated during the equilibrium phase—2.5 minutes after the injection of the contrast) and permit an adequate evaluation of the presence of infiltration of the cervical stroma (CSI), ideally evaluated 4 to 5 minutes after the injection of the contrast.1

MRI is the method of choice for the evaluation of endometrial carcinomas (ECs), from detection to evaluation of recurrent disease. Although the staging of ECs is done surgically using the system of the International Federation of Gynecology and Obstetrics (FIGO), preoperative assessment based on MRI findings helps in risk stratification and decision-making. The main parameters evaluated include the degree and depth of myometrial invasion, parametrial extent, and cervical stromal infiltration. The combination of T2-weighted imaging, dynamic contrast-enhanced MRI, and diffusion-weighted imaging increases the accuracy of EC diagnosis and staging. A proposed step-by-step guide was developed to help the radiologist formulate hypotheses and guide clinical reasoning from the approach of the patient to the preparation of the final report. A structured report is also proposed with the objective of improving report quality and facilitating communication with the treating physicians.

MRI is the method of choice for the evaluation of endometrial carcinomas (ECs), from detection to evaluation of recurrent disease. Although the staging of ECs is done surgically using the system of the International Federation of Gynecology and Obstetrics (FIGO), preoperative assessment based on imaging findings helps in risk stratification and decision-making. The main parameters evaluated include the degree and depth of myometrial invasion, parametrial extent, and cervical stromal infiltration. The combination of T2-weighted imaging, dynamic contrast-enhanced MRI, and diffusion-weighted imaging increases the accuracy of EC diagnosis and staging.

Herein, we present the European Society for Vascular Surgery Guidelines pertinent to the secondary prevention of cerebrovascular events in patients with carotid artery stenosis including lipid lowering therapy, antiplatelet therapy and other risk factor modification. These recommendations are based on current evidence from clinical trials. There is a need for aggressive prevention treatment in patients with carotid artery disease. We also discuss the diagnosis and grading of carotid artery stenosis.

Herein, we present the European Society for Vascular Surgery Guidelines pertinent to the secondary prevention of cerebrovascular events in patients with carotid artery stenosis including lipid lowering therapy, antiplatelet therapy and other risk factor modification. These recommendations are based on current evidence from clinical trials. There is a need for aggressive prevention treatment in patients with carotid artery disease. We also discuss the diagnosis and grading of carotid artery stenosis.

To analyze the role of risk factors associated with moderate or severe airway injuries in children who underwent endotracheal intubation.

In this work, we describe the ability of living hemocytes from an insect (Manduca sexta, Lepidoptera) to hydrolyze extracellular ATP. In these intact cells, there was a low level of ATP hydrolysis in the absence of any divalent metal (8.24 ± 0.94 nmol of Pi/h × 106 cells). The ATP hydrolysis was stimulated by MgCl2 and the Mg2+-dependent ecto-ATPase activity was 15.93 ± 1.74 nmol of Pi/h × 106 cells. Both activities were linear with cell density and with time for at least 90 min. The addition of MgCl2 to extracellular medium increased the ecto-ATPase activity in a dose-dependent manner. At 5 mM ATP, half-maximal stimulation of ATP hydrolysis was obtained with 0.33 mM MgCl2. This stimulatory activity was not observed when Ca2+ replaced Mg2+. The apparent Km values for ATP−4 and Mg-ATP2− were 0.059 and 0.097 mM, respectively. The Mg2+-independent ATPase activity was unaffected by pH in the range between 6.6 and 7.4, in which the cells were viable. However, the Mg2+-dependent ATPase activity was enhanced by an increase of pH. These ecto-ATPase activities were insensitive to inhibitors of other ATPase and phosphatase activities, such as oligomycin, sodium azide, bafilomycin A1, ouabain, furosemide, vanadate, sodium fluoride, tartrate, and levamizole. To confirm the observed hydrolytic activities as those of an ecto-ATPase, we used an impermeant inhibitor, DIDS (4,4′-diisothiocyanostilbene-2,2′-disulfonic acid), as well as suramin, an antagonist of P2-purinoreceptors and inhibitor of some ecto-ATPases. These two reagents inhibited the Mg2+-independent and the Mg2+-dependent ATPase activities to different extents. Interestingly, lipopolysaccharide, a component of cell walls of gram-negative bacteria that increase hemocyte aggregation and phagocytosis, increased the Mg2+-dependent ecto-ATPase activity in a dose-dependent manner but did not modify the Mg2+-independent ecto-ATPase activity.

Organisms and cellular systems are required to adapt to stress conditions like high temperature, often responding by accumulating organic solutes, such as sugars. This accumulation is associated with the effectiveness of these osmolytes in minimizing protein denaturation and membrane damage under stress conditions. In this work, we have studied the effect of sugars on the protection against thermal inactivation of mitochondrial F0F1-ATPase complex, in preparations of submitochondrial particles containing or depleted of inhibitor protein. We observed that after 15 min of pre-incubation at 70 °C of latent MgATP-submitochondrial particles (with inhibitor protein) in the presence of 1.5 ? of sucrose or trehalose, or 3.0 ? of glucose or fructose, about 80% of enzyme activity remained active. In the same conditions, but in the absence of sugars, the activity of the particles was completely abolished. Submitochondrial particles depleted of the inhibitor protein (AS-particles) were almost completely inactivated after 3 min of pre-incubation at 70 °C in the absence of sugars and more than 60% of the enzyme activity remained active when these particles were pre-incubated in the presence of sugars. In such condition, the enzyme acquires a more compact and heat-stable conformation. Sugars, as well as the inhibitor protein, inhibit reversibly F0F1-ATPase complex activity and protect this enzyme against inactivation by high temperature. Interestingly, the protection, promoted by sugars, of particles containing inhibitor protein is higher than of particles depleted of inhibitor protein, suggesting a synergism between sugar and inhibitor protein.

In this work, we describe the ability of living cells of Entamoeba histolytica to hydrolyze extracellular ATP. In these intact parasites, whose viability was determined by motility and by the eosin method, ATP hydrolysis was low in the absence of any divalent metal (78 nmol Pi/h/105 cells). Interestingly, in the presence of 5 mM MgCl2 an ecto-ATPase activity of 300 nmol Pi/h/105 cells was observed. The addition of MgCl2 to the extracellular medium increased the ecto-ATPase activity in a dose-dependent manner. At 5 mM ATP, half-maximal stimulation of ATP hydrolysis was obtained with 1.23 mM MgCl2. Both activities were linear with cell density and with time for at least 1 h. The ecto-ATPase activity was also stimulated by MnCl2 and CaCl2 but not by SrCl2, ZnCl2, or FeCl3. In fact, FeCl3 inhibited both Mg2+-dependent and Mg2+-independent ecto-ATPase activities. The Mg2+-independent ATPase activity was unaffected by pH in the range between 6.4 and 8.4, in which the cells were viable. However, the Mg2+-dependent ATPase activity was enhanced concomitantly with the increase in pH. In order to discard the possibility that the ATP hydrolysis observed was due to phosphatase or 5′-nucleotidase activities, several inhibitors for these enzymes were tested. Sodium orthovanadate, sodium fluoride, levamizole, and ammonium molybdate had no effect on the ATPase activities. In the absence of Mg2+ (basal activity), the apparent Km for ATP4− was 0.053 ± 0.008 mM, whereas at saturating MgCl2 concentrations, the corresponding apparent Km for Mg-ATP2− for Mg2+-dependent ecto-ATPase activity (difference between total and basal ecto-ATPase activity) was 0.503 mM ± 0.062. Both ecto-ATPase activities were highly specific for ATP and were also able to hydrolyze ADP less efficiently. To identify the observed hydrolytic activities as those of an ecto-ATPase, we used suramin, a competitive antagonist of P2 purinoreceptors and an inhibitor of some ecto-ATPases, as well as the impermeant agent 4′-4′-diisothiocyanostylbenzene-2′-2′-disulfonic acid. These two reagents inhibited the Mg2+-independent and the Mg2+-dependent ATPase activities to different extents, and the inhibition by both agents was prevented by ATP. A comparison among the ecto-ATPase activities of three amoeba species showed that the noninvasive E. histolytica and the free-living E. moshkovskii were less efficient than the pathogenic E. histolytica in hydrolyzing ATP. As E. histolytica is known to have a galactose-specific lectin on its surface, which is related to the pathogenesis of amebiasis, galactose was tested for an effect on ecto-ATPase activities. It stimulated the Mg2+-dependent ecto-ATPase but not the Mg2+-independent ATPase activity.

The uncompacted void content of fine aggregate, or fine aggregate angularity (FAA), was introduced in the Superpave mixture design system to screen smooth or rounded fine aggregates that may result in mixtures with low rutting resistance. The assumption is that fine aggregates with lower FAA values have lower shear strength (internal friction) and lower resistance to rutting. Continued implementation and evaluation of the Superpave system has led to numerous questions regarding the validity of this assumption and of the use of the FAA test in general. Nine fine aggregates were used to evaluate the FAA test and to determine whether it was a reliable indicator of fine aggregate shear strength. FAA tests were performed using three gradations and the three standard test methods (A, B, and C). Microscopic analysis was conducted to obtain independent visual measures of angularity and texture. Direct shear tests were performed at four confining stresses to determine shear strength parameters. Results indicated that FAA values were related to visual measures of texture and angularity. However, although FAA value contributed to shear strength, it appeared that other factors such as toughness, gradation, and packing characteristics of the fine aggregate overshadow its effect. For the fine aggregates tested, the FAA test rejected aggregates with high shear strength and accepted aggregates with low shear strength. It was concluded that FAA values alone may not be adequate to assess shear resistance of fine aggregate. Direct shear strength may be a better parameter, but additional work is required to evaluate its validity and feasibility.

The uncompacted void content of fine aggregate, or fine aggregate angularity (FAA), was introduced in the Superpave mixture design system to screen smooth or rounded fine aggregates that may result in mixtures with low rutting resistance. The assumption is that fine aggregates with lower FAA values have lower shear strength (internal friction) and lower resistance to rutting. Continued implementation and evaluation of the Superpave system has led to numerous questions regarding the validity of this assumption and of the use of the FAA test in general. Nine fine aggregates were used to evaluate the FAA test and to determine whether it was a reliable indicator of fine aggregate shear strength. FAA tests were performed using three gradations and the three standard test methods (A, B, and C). Microscopic analysis was conducted to obtain independent visual measures of angularity and texture. Direct shear tests were performed at four confining stresses to determine shear strength parameters. Results indicated that FAA values were related to visual measures of texture and angularity. However, although FAA value contributed to shear strength, it appeared that other factors such as toughness, gradation, and packing characteristics of the fine aggregate overshadow its effect. For the fine aggregates tested, the FAA test rejected aggregates with high shear strength and accepted aggregates with low shear strength. It was concluded that FAA values alone may not be adequate to assess shear resistance of fine aggregate. Direct shear strength may be a better parameter, but additional work is required to evaluate its validity and feasibility.

A complete inactivation is observed after a 3 min pre-incubation at 70 °C with mitochondrial F0F1-ATPase complex depleted of the ATPase natural inhibitor protein (ammonium-Sephadex submitochondrial particles) and activated MgATP-submitochondrial par­ticles (particles that after a 4 h-pre-incubation at 42 °C released the endogenous inhibitor protein). However, latent MgATP-submitochondrial particles (particles containing the inhibi­tor protein) pre-incubated under the same conditions are totally inactivated only after 15 min of pre-incubation. When ammonium-Sephadex particles are reconstituted with 20 µg/ml of purified ATPase inhibitor protein there is an increase of 15-fold in the half-time for ther­mal inactivation (t0.5), showing that the inhibitor protein protects the mitochondrial F0F1-ATPase complex against thermal inactivation.

This study shows that incubation of rat liver mitochondria in the presence of the thiol/ amino reagent 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DID S) is followed by inhibition of both succinate supported respiration and oxidative phosphorylation. Half-maximal inhibition of succinic dehydrogenase activity and succinate oxidation by mitochondria was attained at 55.3 and 60.8 µm DIDS, respectively. DIDS did inhibit the net ATP synthesis and ATP ? [32P]Pi exchange reaction catalyzed by submitochondrial particles in a dose-dependent manner (Ki= 31.7 µm and Ki= 32.7 µm), respectively. The hydrolytic activities of uncoupled heart submitochondrial particles and purified F1-ATPase were also inhibited 50% by 31.9 and 20.9 µm DIDS, respectively.

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No relevant conflicts of interest to declare.

Thomas: ERYTECH Pharma: Consultancy. Bertrand:ERYTECH Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vey:Celgene: Honoraria; Roche: Honoraria; Janssen: Honoraria. Bonin:ERYTECH Pharma: Employment. Godfrin:ERYTECH Pharma: Employment. El Hariry:ERYTECH Pharma: Employment.

Bertrand: ERYTECH Pharma: Consultancy. Thomas:ERYTECH Pharma: Consultancy. Vey:Roche: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Bonin:ERYTECH Pharma: Employment. El Hariry:ERYTECH Pharma: Employment.

Background

Background

Background

Bertrand: ERYTECH Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Thomas:ERYTECH Pharma: Consultancy. Vey:Celgene: Honoraria; Roche: Honoraria; Janssen: Honoraria. Bonin:ERYTECH Pharma: Employment. Godfrin:ERYTECH Pharma: Employment. El Hariry:ERYTECH Pharma: Employment.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Introduction

As clinical trials for relapsed Acute Myeloid Leukaemia (AML) patients do not accurately reflect the daily clinical reality, data regarding the outcome of these patients is scarce. We thus conducted a retrospective analysis to quantify the prospects of salvage treatment of primary refractory or first-relapse AML patients and to assess the contribution of allograft and intensive treatment regimens with respect to major risk groups in a real-life setting.We performed a retrospective analysis of 163 patients diagnosed from 2005-2012, in 5 haematological centres in the north of France (Lille, Amiens, Roubaix, Valenciennes and Lens). We considered every patient in that time frame who was treated following an intensive pathway. Statistical analysis as performed using Kaplan-Meier survival analysis and logrank test in the SPSS softwareThe mean age at diagnosis was 45 (range 16-70 years) and the median age at relapse was 48 (ranging 17-70 years). The median time from diagnosis to relapse was 8 months. 20.6% of patients were considered primary refractory (relapse within 60 days from diagnosis). The median overall survival was 28 months (95% CI was 17-38 months). There was no statistically significant survival difference between primary refractory patients and first relapsed patients. Unsurprisingly, survival was significantly (p<0.05) higher in the transplanted patients (48 months) than in the non-transplanted group (19 months) and in those who achieved CR (48 months) than in those who didn’t (14 months). Risk stratification was established using the European Leukaemia Network (ELN) classification and the repartition was as followed: favourable (14.3%), intermediate I (18.3%), intermediate II (41.8%) and unfavourable (23.5%). 65% of patients achieved a complete remission (CR). This percentage varied by risk group as follows: favorable (84%), intermediate I (67%), intermediate II (59%) and adverse (39%). Median overall survivals were not statistically significantly different in between the groups but there was a trend suggesting than intermediate I performed poorly (median OS: 19months versus 48 months for favourable, 35 for intermediate II and 18 months for unfavourable patients). When considering treatment regimens, there were no significant difference between the regimens used (Mitoxantrone-Cytarabine-Quinine (MAQ) (n=26), Amsacrine-Cytarabine (n=62), Fludarabine-Cytarabine-Mitoxantrone (FLAN)(n=24), Idarubicine or Daunorubicine Cytarabine (n=21), Clofarabine-Cytarabine (n=4), Mylotarg based (n=9) and other (HDAC, Cytarabine as a single agent)(n=16). The median OS for these groups were respectively 16, 44, 24, not reached, 20, 21 and 11 months. Further analysis is hindered by the size of the groups.This data suggests that for patients with favourable disease delaying transplant to first relapse and treating them with intensive salvage regimen is a valuable option. High risk patients still perform poorly. The relative low representation of these patients (23.6%) is probably due to the fact that these patients are transplanted upfront and often not treated using intensive regimens at relapse. Discussion remains for the intermediate patients. In our study, although numbers are small, they do not seem to behave similarly. The outcome of intermediate I patients resembles more unfavourable patients: this should be considered when discussing both upfront transplantation and management at first relapse.This data suggests that delaying transplant for low risk patients is feasible and associated with a good outcome. Salvage intensive chemotherapy and transplant is an effective approach for these patients. Intermediate I patients behave like unfavourable patients and should thus be considered for upfront transplantation and experimental treatments.Preudhomme: CELGENE: Research Funding. Quesnel:CELGENE: Research Funding. Berthon:CELGENE: Research Funding.

As clinical trials for relapsed Acute Myeloid Leukaemia (AML) patients do not accurately reflect the daily clinical reality, data regarding the outcome of these patients is scarce. We thus conducted a retrospective analysis to quantify the prospects of salvage treatment of primary refractory or first-relapse AML patients and to assess the contribution of allograft and intensive treatment regimens with respect to major risk groups in a real-life setting.