Les points essentiels des nouvelles recommandations internationales pour la prise en charge de la maladie thromboembolique veineuse chez les patients atteints de cancer

La maladie thromboembolique veineuse (MTEV) associée au cancer est la deuxième cause de décès chez les patients cancéreux après la progression de la maladie [1]. L’incidence de la MTEV associée au cancer augmente dans le monde entier. Les patients atteints de cancer sont quatre à sept fois plus susceptibles de développer une MTEV que les patients sans cancer [2, 3]. Plusieurs facteurs sont responsables de cette augmentation de l'incidence de la MTEV, notamment le type de cancer, l'utilisation de cathéters veineux centraux pour la chimiothérapie et d'autres traitements anticancéreux chirurgicaux et médicaux associés comme la radiothérapie, les agents antiangiogéniques, médicaments immunomodulateurs, la thérapie hormonale et les agents de stimulation de l’érythropoïèse) [4, 5, 6].Le traitement de la TEV établie chez les patients atteints de cancer est complexe. La chimiothérapie systémique peut entraîner des interactions médicamenteuses qui pourraient altérer l'efficacité des traitements anticancéreux ou des anticoagulants oraux, et pourraient également provoquer une thrombopénie, ce qui augmente le risque de saignement [7]. Déterminer la nécessité d'une prophylaxie de la MTEV chez les patients atteints de cancer est un autre défi en raison des risques très variables de risques thrombotique et hémorragique selon les différents types de cancer, les différents stades de la maladie et les traitements anticancéreux [7].L'initiative internationale sur la thrombose et le cancer (International Initiative on Thrombosis and Cancer « ITAC ») a élaboré les premières directives internationales fondées sur des données probantes en 2013 pour fournir aux cliniciens des recommandations pratiques et accessibles pour le traitement et la prévention de la thrombose associée au cancer. Ces recommandations ont été mises à jour en 2016 et ensuite approuvées par la Société internationale sur la thrombose et l'hémostase (International Society on Thrombosis and Haemostasis « ISTH »). Une mise à jour 2019 de ces lignes directrices élaborées par un groupe d’experts internationaux, en lien avec l’Institut National du Cancer (INCa), selon une approche « Grading of Recommendations Assessment, Development and Evaluation » a été publiée dans le Lancet Oncology en septembre 2019. La méthodologie et le manuscrit et le manuscrit ont été revus et validés par l’ISTHLa maladie thromboembolique veineuse (MTEV) associée au cancer est la deuxième cause de décès chez les patients cancéreux après la progression de la maladie [1]. L’incidence de la MTEV associée au cancer augmente dans le monde entier. Les patients atteints de cancer sont quatre à sept fois plus susceptibles de développer une MTEV que les patients sans cancer [2, 3]. Plusieurs facteurs sont responsables de cette augmentation de l'incidence de la MTEV, notamment le type de cancer, l'utilisation de cathéters veineux centraux pour la chimiothérapie et d'autres traitements anticancéreux chirurgicaux et médicaux associés comme la radiothérapie, les agents antiangiogéniques, médicaments immunomodulateurs, la thérapie hormonale et les agents de stimulation de l’érythropoïèse) [4, 5, 6].Le traitement de la TEV établie chez les patients atteints de cancer est complexe. La chimiothérapie systémique peut entraîner des interactions médicamenteuses qui pourraient altérer l'efficacité des traitements anticancéreux ou des anticoagulants oraux, et pourraient également provoquer une thrombopénie, ce qui augmente le risque de saignement [7]. Déterminer la nécessité d'une prophylaxie de la MTEV chez les patients atteints de cancer est un autre défi en raison des risques très variables de risques thrombotique et hémorragique selon les différents types de cancer, les différents stades de la maladie et les traitements anticancéreux [7].L'initiative internationale sur la thrombose et le cancer (International Initiative on Thrombosis and Cancer « ITAC ») a élaboré les premières directives internationales fondées sur des données probantes en 2013 pour fournir aux cliniciens des recommandations pratiques et accessibles pour le traitement et la prévention de la thrombose associée au cancer. Ces recommandations ont été mises à jour en 2016 et ensuite approuvées par la Société internationale sur la thrombose et l'hémostase (International Society on Thrombosis and Haemostasis « ISTH »). Une mise à jour 2019 de ces lignes directrices élaborées par un groupe d’experts internationaux, en lien avec l’Institut National du Cancer (INCa), selon une approche « Grading of Recommendations Assessment, Development and Evaluation » a été publiée dans le Lancet Oncology en septembre 2019.  La méthodologie et le manuscrit et le manuscrit ont été revus et validés par l’IST

Assessment of corroded API 5L X52 pipe elbow using a modified failure assessment diagram

Pipe elbows (bends) are considered critical pressurized components in the piping systems and pipelines due to their stress intensification and the effect of bend curvature. They are prone and hence more exposed to different corrosion failure modes than straight pipes. Late detection of such elbow damages can lead to different dangerous and emergency situations which cause environmental disasters, pollution, substantial consumer losses and a serious threat to human life. A comprehensive safety and reliability assessment of pipe elbows, including usage of prediction models, can provide significant increases in the service life of pipelines. It is well known that the limit pressure is an important parameter to assess the piping integrity. In this paper, the integrity assessment of damaged pipeline elbows made of API 5L X52 steel was done within the framework of numerical modeling using the finite element method (FEM) and finite element analysis (FEA). The evaluation of numerically FEM modeled limit pressure in the corroded elbow containing a rectangular parallelepiped-shaped corrosion defect with rounded corners at the intrados section was done and compared to different codes for calculating limit pressure. Moreover, the area with the corrosion defects with different relative defect depth to wall thickness ratios was FEM modeled at the intrados section of the pipe elbow where the highest hoop stress exists. The results showed that the codes for straight pipes could not be applied for the pipe elbows due to the significantly higher error in the obtained limit pressure value compared with numerically FEM obtained results. However, the results for modified codes, adapted for the pipe elbow case using the Goodall formula for calculation of the hoop stress in pipe elbows with defects are pretty consistent with the numerical FEA results. The notch failure assessment diagram (NFAD) was also used for the straight pipe and pipe bends with different corrosion defect depth ratios, while the obtained critical defect depth ratios further highlighted the criticality of pipe elbows as an essential pipeline component

Exercise in type 2 diabetes: to resist or to endure?

There is now evidence that a single bout of endurance (aerobic) or resistance exercise reduces 24 h post-exercise subcutaneous glucose profiles to the same extent in insulin-resistant humans with or without type 2 diabetes. However, it remains to be determined which group would benefit most from specific exercise protocols, particularly with regard to long-term glycaemic control. Acute aerobic exercise first accelerates translocation of myocellular glucose transporters via AMP-activated protein kinase, calcium release and mitogen-activated protein kinase, but also improves insulin-dependent glucose transport/phosphorylation via distal components of insulin signalling (phosphoinositide-dependent kinase 1, TBC1 domain family, members 1 and 4, Rac1, protein kinase C). Post-exercise effects involve peroxisome-proliferator activated receptor-γ coactivator 1α and lead to ATP synthesis, which may be modulated by variants in genes such as NDUFB6. While mechanisms of acute resistance-type exercise are less clear, chronic resistance training activates the mammalian target of rapamycin/serine kinase 6 pathway, ultimately increasing protein synthesis and muscle mass. Over the long term, adherence to rather than differences in metabolic variables between specific modes of regular exercise might ultimately determine their efficacy. Taken together, studies are now needed to address the variability of individual responses to long-term resistance and endurance training in real life

EMG-Normalised Kinase Activation during Exercise Is Higher in Human Gastrocnemius Compared to Soleus Muscle

In mice, certain proteins show a highly confined expression in specific muscle groups. Also, resting and exercise/contraction-induced phosphorylation responses are higher in rat skeletal muscle with low mitochondrial content compared to muscles with high mitochondrial content, possibly related to differential reactive oxygen species (ROS)-scavenging ability or resting glycogen content. To evaluate these parameters in humans, biopsies from soleus, gastrocnemius and vastus lateralis muscles were taken before and after a 45 min inclined (15%) walking exercise bout at 69% VO2max aimed at simultaneously activating soleus and gastrocnemius in a comparable dynamic work-pattern. Hexokinase II and GLUT4 were 46–59% and 26–38% higher (p<0.05) in soleus compared to the two other muscles. The type I muscle fiber percentage was highest in soleus and lowest in vastus lateralis. No differences were found in protein expression of signalling proteins (AMPK subunits, eEF2, ERK1/2, TBC1D1 and 4), mitochondrial markers (F1 ATPase and COX1) or ROS-handling enzymes (SOD2 and catalase). Gastrocnemius was less active than soleus measured as EMG signal and glycogen use yet gastrocnemius displayed larger increases than soleus in phosphorylation of AMPK Thr172, eEF2 Thr56 and ERK 1/2 Thr202/Tyr204 when normalised to the mean relative EMG-signal. In conclusion, proteins with muscle-group restricted expression in mice do not show this pattern in human lower extremity muscle groups. Nonetheless the phosphorylation-response is greater for a number of kinase signalling pathways in human gastrocnemius than soleus at a given activation-intensity. This may be due to the combined subtle effects of a higher type I muscle fiber content and higher training status in soleus compared to gastrocnemius muscle

Chronic CaMKII inhibition blunts the cardiac contractile response to exercise training

Activation of the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a critical role modulating cardiac function in both health and disease. Here, we determined the effect of chronic CaMKII inhibition during an exercise training program in healthy mice. CaMKII was inhibited by KN-93 injections. Mice were randomized to the following groups: sham sedentary, sham exercise, KN-93 sedentary, and KN-93 exercise. Cardiorespiratory function was evaluated by ergospirometry during treadmill running, echocardiography, and cardiomyocyte fractional shortening and calcium handling. The results revealed that KN-93 alone had no effect on exercise capacity or fractional shortening. In sham animals, exercise training increased maximal oxygen uptake by 8% (p < 0.05) compared to a 22% (p < 0.05) increase after exercise in KN-93 treated mice (group difference p < 0.01). In contrast, in vivo fractional shortening evaluated by echocardiography improved after exercise in sham animals only: from 25 to 32% (p < 0.02). In inactive mice, KN-93 reduced rates of diastolic cardiomyocyte re-lengthening (by 25%, p < 0.05) as well as Ca2+ transient decay (by 16%, p < 0.05), whereas no such effect was observed after exercise training. KN-93 blunted exercise training response on cardiomyocyte fractional shortening (63% sham vs. 18% KN-93; p < 0.01 and p < 0.05, respectively). These effects could not be solely explained by the Ca2+ transient amplitude, as KN-93 reduced it by 20% (p < 0.05) and response to exercise training was equal (64% sham and 47% KN-93; both p < 0.01). We concluded that chronic CaMKII inhibition increased time to 50% re-lengthening which were recovered by exercise training, but paradoxically led to a greater increase in maximal oxygen uptake compared to sham mice. Thus, the effect of chronic CaMKII inhibition is multifaceted and of a complex nature

Increased Plasticity in Invasive Populations of a Globally Invasive Cactus

Biological invasions pose global threats to biodiversity and ecosystem functions. Invasive species often display a high degree of phenotypic plasticity, enabling them to adapt to new environments. This study examines plasticity to water stress in native and invasive Opuntia ficus-indica populations, a prevalent invader in arid and semi-arid ecosystems. Through controlled greenhouse experiments, we evaluated three native and nine invasive populations. While all plants survived the dry treatment, natives exhibited lower plasticity to high water availability with only a 36% aboveground biomass increase compared to the invasives with a greater increase of 94%. In terms of belowground biomass, there was no significant response to increased water availability for native populations, but plants from the invasive populations showed a 75% increase from the dry to the wet treatment. Enhanced phenotypic plasticity observed in invasive populations of O. ficus-indica is likely a significant driver of their success and invasiveness across different regions, particularly with a clear environmental preference towards less arid conditions. Climate change is expected to amplify the invasion success due to the expansion of arid areas and desertification. Opuntia ficus-indica adapts to diverse environments, survives dry spells, and grows rapidly in times of high-water supply, making it a candidate for increased invasion potential with climate change

La province des complexes annulaires alcalins sursaturés de l'Adrar des Iforas, Mali

IF=1.219info:eu-repo/semantics/publishe