Ultrasound arterial anomalies in patients exposed to nilotinib therapy for chronic myeloid leukemia.

INTRODUCTION: Patients exposed to nilotinib for chronic myeloid leukemia (CML) appear to be at risk of arterial complication. The prevalence and aspect of ultrasound asymptomatic arterial lesions are unknown. OBJECTIVE: To describe prevalence and characteristics of ultrasound arterial anomalies in patients treated with nilotinib for CML. METHODS: Patients treated with nilotinib from 2006 to 2015 in the department of the Paoli-Calmettes Institute, Marseille, were included retrospectively. A vascular ultrasound screening was carried out from 2010. The arterial lesions at the first examination were described: plaque and its echogenicity, stenosis or occlusion. A vascular arterial anomaly (VAA) was defined by the presence of a clinical and/or ultrasound anomaly. Patients with or without VAA at initial vascular examination were compared using bivariate and multivariate analysis. RESULTS: 74 patients were included (51.4% men, mean age 54.5 years); 25 patients had ultrasound arterial anomalies (33.8%). Carotid bulb was the most involved territory (44%). Arterial anomalies were: 88% plaques, 44%>50% stenosis and 12% occlusion. 72.7% plaques were echolucent or hypoechogenic. A VAA was present in 25 patients with initial vascular evaluation (33.8%). Patients with VAA at baseline were significantly older (64.9 vs 49.3, P<0.001), older at nilotinib initiation (60.8 vs 46.5, P<0.001), with more arterial hypertension (40% vs 12.2%, P=0.01), with more cardiovascular risk factors (P=0.03). In patient with no cardiovascular risk factor 12.5% had VAA (n=24). CONCLUSION: Nilotinib seems to be associated to arterial lesions of unstable lipid-like appearance. The most involved arterial territory was the carotid bulb and the most common lesion was echolucent or hypoechogenic plaque. VAA can occur in patients without cardiovascular risk factors. This result encourages us to systematically screen and follow all patients exposed to nilotinib even those without cardiovascular risk factors.

Descriptive study of the general practitioners' perception of direct oral anticoagulants and the risk of genital bleeding in women of childbearing age.

AIM OF THE STUDY AND PATIENTS: Direct oral anticoagulants (DOA) tend to replace antivitamins K (VKA). The incidence of major and minor hemorrhages is higher in women, a difference potentially linked to genital hemorrhages. The objective is to assess the practices and perception of general practitioners of the use of oral anticoagulant therapy in women of childbearing age. MATERIALS AND METHODS: Descriptive, observational, transversal and monocentric study. An 11-items questionnaire was sent to 900 randomized general practitioners, assessing the type of patient, the type of anticoagulant prescribed, the management of genital bleeding, and the assessment of the quality of life of anticoagulated patients. RESULTS: DOA were the most prescribed anticoagulants. Genital hemorrhage was the second leading cause of minor hemorrhage. Most doctors (60.6%) believed they were due to VKAs. 25% reported an alteration in the quality of life of patients following these genital hemorrhages and 47.5% addressed this subject in consultation. CONCLUSION: Our study suggests that, according to the general practitioners interviewed, genital hemorrhage is more frequent on VKA than on DOA in women of reproductive age, which is contradictory with the data in the literature. The probably taboo subject is rarely mentioned in consultation and is responsible for a deterioration in the quality of life in these young patients. No recommendation exists on the management of this type of genital hemorrhage in these women. An algorithm is proposed for their management.

Reduction of visual acuity decreases capacity to evaluate radiographic image quality.

INTRODUCTION: To determine the impact of reduced visual acuity on the evaluation of a test object and appendicular radiographs. METHODS: Visual acuity was reduced by two different magnitudes using simulation glasses and compared to normal vision (no glasses). During phase one phantom images were produced for the purpose of counting objects by 13 observers and on phase 2 image appraisal of anatomical structures was performed on anonymized radiographic images by 7 observers. The monitors were calibrated (SMPTE RP133 test pattern) and the room lighting was maintained at 7 ± 1 lux. Image display and data on grading were managed using ViewDEX (v.2.0) and the area under the visual grading characteristic (AUCVGC) was calculated using VGC Analyzer (v1.0.2). Inferential statistics were calculated using SPSS. RESULTS: For the evaluation of appendicular radiographs the total interpretation time was longer when visual acuity was reduced with 2 pairs of simulation glasses (15.4 versus 8.9 min). Visual grading analysis showed that observers can lose the ability to detect anatomical and contrast differences when they have a simulated visual acuity reduction, being more challenging to differentiate low contrast details. No simulation glasses, compared to 1 pair gives an AUCVGC of 0.302 (0.280, 0.333), that decreases to 0.197 (0.175, 0.223) when using 2 pairs of glasses. CONCLUSIONS: Reduced visual acuity has a significant negative impact on the evaluation of test objects and clinical images. Further work is required to test the impact of reduced visual acuity on visual search, technical evaluation of a wider range of images as well as pathology detection/characterization performance. IMPLICATIONS FOR PRACTICE: It seems that visual performance needs to be considered to reduce the risks associated with incomplete or incorrect diagnosis. If employers or professional bodies were to introduce regular eye tests into health screening it may reduce the risk of misinterpretation as a result of poor vision.

[Evaluation of an "Emergency Thrombosis" care system in a university-hospital department of general emergencies]. / Évaluation de la mise en place d'une filière de soins « Urgence Thrombose ¼ dans un service hospitalo-universitaire d'Urgences générales.

GOAL: Describe the use of diagnostic, prognostic and therapeutic algorithms for venous thromboembolism (VTE), derived from the 2014 European guidelines, in a teaching hospital's emergencies department and compare two groups: the 2015 group "without a care path" and the 2017 group "with a care path". METHOD: Comparative and retrospective study of the characteristics of emergencies department patients admitted for VTE from January to June 2015 for the 2015 group and from January to June 2017 for the 2017 group. RESULTS: Seventy-nine patients were included in the 2015 group and 62 patients in the 2017 group. In 24% of cases a clinical probability rule was calculated in the 2017 group (vs. no score in 2015, P<0.05). In the 2015 group, 10% of patients did not have a D-Dimer measurement in case of low clinical probability (vs. 0% in 2017, P<0.05). For both groups, the severity score sPESI was not noted in the medical record. All patients with pulmonary embolism were hospitalized in both groups. A total of 36% of patients with deep vein thrombosis (DVT) were hospitalized in the 2015 group (vs. none in 2017, P<0.05). A total of 52.5% of patients were treated with direct oral anticoagulants (DOAS) in the 2017 group vs. 32.5% in the 2015 group (P<0.05). In 18% of cases DOAS were prescribed by emergency physicians in the 2017 group vs. 2.5% in the 2015 group (P<0.05). Mean hospital stay was 7.4 days in the 2017 group and 9.4 days in the 2015 group (P<0.05). CONCLUSION: We observed a change in clinical practices and prescriptions after the establishment of an "Emergency Thrombosis" care system. Indeed, improvement in the calculation of the clinical probability score, increase in the outpatient management of DVT, increase in prescribing DOAS and reducing the length of hospital stay were the main revisions. The implementation of standardized digitally calculated clinical and prognostic probability scores would optimize this care path, as well as allow a better distribution of the post-emergency consultations created for outpatients.

[PASTIS study: Evaluation of an automated office blood pressure measurement]. / Étude PASTIS : pression artérielle sans intervention de soignant. Évaluation d'une mesure de la pression artérielle automatisée en cabinet.

OBJECTIVE: The evaluation of automated office blood pressure (AOBP) measurement compared to 24-hour ambulatory BP monitoring (ABPM), Home BP measurement and manual BP. PATIENTS AND METHODOLOGY: A total of 123 hypertensive patients were included. Overall, 68 completed the 4 measurement: Manual BP in the office (Omron 705 CP 3 measurements), ABPM (Spacelab of 96 measurement/per 24hours), Home BP (18 measurement during 3 days), AOBP using the SPRINT methodology: lying patient, isolated with an automatic measurement (Dinamap) every minutes during 8minutes (average of the last 3 measurement). Twenty-two out of 123 patients (26%) did not complete the Home BP measurement. RESULTS: The average of AOBP measurement using SPRINT is 132±12/69±9mmHg, of ABPM 134±13/79±9, of Home BP: 135±13/70±13 and of manual BP: 138±13/72±11mmHg The Bland & Altman method highlight that the AOBP, the ABPM and home BP measurement are 3 substitutable methods. The confidence interval is smaller between the ABPM and the AOBP than with the home BP. CONCLUSION: The automated office blood pressure, as the Home BP measurement, can be considered a reliable substitute for the ABPM, when the later is not accessible, and when a repeated therapeutic evaluation is needed, or when the home BP measurement is not done. These results encourage us to use it more frequently as the Canadian Hypertension Education Program recommend it.

[Quality standards for ultrasonographic assessment of peripheral vascular malformations and vascular tumors. Report of the french society for vascular medicine. 2018 Update]. / Standards de qualité pour la pratique de l'examen écho-Doppler dans l'étude des malformations et tumeurs vasculaires. Rapport de la Société française de médecine vasculaire (SFMV) : actualisation 2018.

The quality standards of the French Society of Vascular Medicine for the ultrasonographic assessment of vascular malformations are based on the two following requirements: (1) technical know-how: mastering the use of ultrasound devices and the method of examination; (2) medical know-how: ability to adapt the methods and scope of the examination to its clinical indication and purpose, and to rationally analyze and interpret its results. AIMS OF THE QUALITY STANDARDS: To describe an optimal method of examination in relation to the clinical question and hypothesis. To homogenize practice, methods, glossary, and reporting. To provide good practice reference points, and promote a quality process. ITEMS OF THE QUALITY STANDARDS: The 3 levels of examination; their clinical indications and goals. The reference standard examination (level 2), its variants according to clinical needs. The minimal content of the examination report; the letter to the referring physician (synthesis, conclusion and proposal for further investigation and/or therapeutic management). Commented glossary (anatomy, hemodynamics, semiology). Technical bases. Setting and use of ultrasound devices. Here, we discuss ultrasonography methods of using of ultrasonography for the assessment of peripheral vascular malformations and tumors (limbs, face, trunk).

PtI2(DACH), the iodido analogue of oxaliplatin as a candidate for colorectal cancer treatment: chemical and biological features.

Colorectal cancer (CRC) is a global health problem being the fourth most common cause of death due to cancer worldwide. Oxaliplatin plays a key role in current CRC treatment but shows serious drawbacks, such as a high systemic toxicity and the frequent insurgence of Pt resistance. In search of novel and more efficacious Pt-based drugs for CRC treatment, we synthesized and characterised PtI2(DACH), an oxaliplatin analogue. PtI2(DACH) was obtained through the replacement of bidentate oxalate with two iodides. PtI2(DACH) turned out to be more lipophilic than oxaliplatin, a fact that led to an enhancement of its cellular uptake. In contrast to oxaliplatin, PtI2(DACH) showed a scarce reactivity towards model proteins, while maintaining affinity for a standard DNA oligo. Notably, PtI2(DACH) induced cytotoxicities roughly comparable to those of oxaliplatin in three representative CRC cell lines. Moreover, it was able to trigger cell apoptosis, to an extent even better than cisplatin and oxaliplatin. Overall, a rather promising picture emerges for this novel Pt drug that merits, in our opinion, a deeper and more extensive preclinical evaluation.

[Prevalence and severity of hypertensive emergencies and outbreaks in the hospital emergency department of CHU Timone at Marseille: Follow-up in three months of hospitalized patients]. / Prévalence et gravité des urgences et des poussées hypertensives dans le service d'urgence hospitalière du CHU La Timone de Marseille : suivi à trois mois des patients hospitalisés.

GOAL: Evaluation of the prevalence and severity of hypertensive emergencies and crisis in an Emergency Service of Timone hospital in Marseille and follow-up of 3 months of hospitalized emergencies. METHODS: This study was conducted in the Emergency Department between April 1 and June 30, 2015. All patients with BP>180 and/or 110mmHg was recorded and classified in true emergencies (presence of visceral pain) and hypertensive isolated crisis. A phone follow-up patients was organized. RESULTS: During this period, 170 patients were identified: 95 (56%) hypertensive crisis and 75 (44%) hypertensive emergencies: 25 OAP (33%), 18 ischemic stroke (24%), 15 hemorrhagic stroke (20%), 9 angina (12%) and 8 different. The clinical characteristics of hypertensive emergencies are preferentially dyspnea (27%) motor deficit (36%), and chest pain (16%). The BP of hypertensive emergencies at their admission (3 measurements, oscillometric automatic device) is close to the hypertensive crisis (198.17±19.3 to 96.4±21.2mmHg versus 191±31.6 to 96.12±21). The BP controlled after 15minutes of rest is lower for crisis compared to real emergencies (152±47 to 79±28 vs. 174±31 to 86±26). Age emergency is larger (77±14 vs. 67±17), the number of slightly larger drug (1.79 versus 1.67±1±1). Telephone follow-up was performed after an average period of three months. Ninety-nine patients were contacted by telephone: 46 patients who were admitted for hypertensive emergency patients and 53 for a push. Eighteen deaths have been recorded, including 15 among hypertensive emergencies (9 in hemorrhagic stroke, 5 for ischemic stroke, and 1 for OAP) with 5-hospital deaths within 48hours after admission and 10 within 3 months in patients hospitalized with hypertensive emergency or 33%. Seventy-seven patients out of 99 had been reviewed by their attending physicians. A questionnaire was sent by mail to patients who have not answered the phone contacts, and responses are pending. CONCLUSION: Hypertensive emergencies hospitalized in Timone Hospital represent 44% of patients hospitalized for emergency HTA. Their gravity is 1/3 since most patients die within three months warranting closer management of these fragile patients by creating a specialized consulting postemergency.

A lysigenic programmed cell death-dependent process shapes schizogenously formed aerenchyma in the stems of the waterweed Egeria densa.

BACKGROUND AND AIMS: Plant adaptation to submergence can include the formation of prominent aerenchyma to facilitate gas exchange. The aim of this study was to characterize the differentiation of the constitutive aerenchyma in the stem of the aquatic macrophyte Egeria densa (Hydrocharitaceae) and to verify if any form of cell death might be involved. METHODS: Plants were collected from a pool in a botanical garden. Aerenchyma differentiation and apoptotic hallmarks were investigated by light microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay coupled with genomic DNA extraction and gel electrophoresis (DNA laddering assay). Cell viability and the occurrence of peroxides and nitric oxide (NO) were determined histochemically using specific fluorogenic probes. KEY RESULTS: Aerenchyma differentiation started from a hexagonally packed pre-aerenchymatic tissue and, following a basipetal and centripetal developmental pattern, produced a honeycomb arrangement. After an early schizogenous differentiation process, a late lysigenous programmed cell death- (PCD) dependent mechanism occurred. This was characterized by a number of typical apoptotic hallmarks, including DNA fragmentation, chromatin condensation, apoptotic-like bodies, partial cell wall lysis and plasmolysis. In addition, local increases in H2O2 and NO were observed and quantified. CONCLUSIONS: The differentiation of cortical aerenchyma in the stem of E. densa is a complex process, consisting of a combination of an early schizogenous differentiation mechanism and a late lysigenous PCD-dependent process. The PCD remodels the architecture of the gas spaces previously formed schizogenously, and also results in a reduction of O2-consuming cells and in recycling of material derived from the lysigenic dismantling of the cells.

Trace metals, peroxidase activity, PAHs contents and ecophysiological changes in Quercus ilex leaves in the urban area of Caserta (Italy).

Trace metals and polycyclic aromatic hydrocarbons, severely affecting human, animal and plants health, highly contribute to the air pollution in urban areas mainly due to car traffic. In this study the air biomonitoring of the city of Caserta (South Italy) has been performed by using Quercus ilex L., a widespread ornamental plant in parks, gardens and avenues. The plant leaves from different sites within the urban area were collected and used to determine the concentrations of V, Cd, Cr, Pb, Ni, Cu, and PAHs as well as the free amino acid content and peroxidase enzyme activity as indices of the leaf physiological conditions. All the tested trace metals showed concentrations higher than the control site. Lead was positively correlated to Cd and Cr and showed, also, a positive trend with Ni and Cu that, in their turn, were highly correlated between them. Positive and significant correlations were evidenced between total PAHs and carcinogenic PAHs and negative correlations between those and all trace metals assayed except V. Cu and Cd contents evidence negative correlations with peroxidase activity, and the free amino acid contents. The PAHs, in particular Carc-PAHs, were negatively correlated to the tested heavy metals. POD was positively correlated only with V and negatively correlated with Cu and Cd.

Priming of late endothelial progenitor cells with erythropoietin before transplantation requires the CD131 receptor subunit and enhances their angiogenic potential.

BACKGROUND: Endothelial colony-forming cells (ECFCs) are promising candidates for cell therapy of ischemic diseases. Erythropoietin (EPO) is a cytokine that promotes angiogenesis after ischemic injury. EPO receptors (EPORs) classically include two EPOR subunits, but may also associate with the ß-common chain (CD131) in a newly identified receptor involved in EPO cytoprotective effects. OBJECTIVE: The aim was to take advantage of the proangiogenic properties of EPO to enhance ECFC graft efficiency. We postulated that priming ECFCs by adding epoietin α in culture medium prior to experiments might increase their angiogenic properties. We also explored the role of the CD131 subunit in EPO priming of ECFCs. METHODS AND RESULTS: By western blotting on cord blood ECFC lysates, we showed that EPOR and CD131 expression increased significantly after EPO priming. These proteins coimmunoprecipitated and colocalized, suggesting that they are covalently bound in ECFCs. EPO at 5 IU mL(-1) significantly stimulated proliferation, wound healing, migration and tube formation of ECFCs. EPO priming also increased ECFC resistance to H2 O2-induced apoptosis and survival in vivo. Similarly, in vivo studies showed that, as compared with non-primed ECFC injection, 5 IU mL(-1) EPO-primed ECFCs, injected intravenously 24 h after hindlimb ischemia in athymic nude mice, increased the ischemic/non-ischemic ratios of hindlimb blood flow and capillary density. These effects were all prevented by CD131 small interfering RNA transfection, and involved the phosphoinositide 3-kinase-Akt pathway. CONCLUSION: These results highlight the potential role of EPO-primed ECFCs for cell-based therapy in hindlimb ischemia, and underline the critical role of CD131 as an EPO coreceptor.

[Postexercise duplex ultrasound to diagnose external iliac endofibrosis]. / Endofibrose de l'artère iliaque externe diagnostiquée par écho-doppler post-effort.

Arterial endofibrosis is a disease of recent discovery which concerns high-performance athletes, predominantly competitive cyclists. The preferential location is the external iliac artery. The symptoms are diverse (pain, edema, paresthesia), always linked to an effort. The diagnosis may be delayed due to atypical symptoms in athletes. Complementary tests are measure of the systolic pressure index after exercise, duplex ultrasound, CT angiography, MR angiography and arteriography. We report a case of endofibrosis where late diagnosis was established with postexercise duplex ultrasound, while CT angiography and arteriography failed to reveal characteristic abnormalities.

Heavy metal content in sediments along the Calore river: relationships with physical-chemical characteristics.

In the present study, trace metals contents (V, Cr, Mn, Fe, Ni, Cu, Zn, Cd and Pb) and physico-chemical parameters (nitrogen, organic and inorganic carbon, pH and particle size) in sediments samples along the Calore river were analyzed in two seasons. Sediment samples were collected in ten sites upstream and downstream of the city of Benevento and its industrial area, the confluence of Sabato and Tammaro tributaries, and the confluence of Calore and Volturno rivers. The highest contents of trace metals were found, generally, in the sites immediately downstream of industrial area and of Benevento city. The sites on the Tammaro and Sabato also showed relatively high contents of Ni and, only for Sabato sites, of Cr, and Fe. With the exception of Cd, the heavy metal contents were highest in the last site of Calore river, which therefore is a source of pollution to the Volturno river. Besides the sites downstream of Benevento city showed the higher pH values and also the highest contents of fine particles size and organic matter. Positive correlations among trace metals, organic substance, particle size sediments were found. The data obtained in this study were analyzed with reference to Interim Sediment Quality Guidelines and indicated moderate-to-high pollution by some trace metals (V, Cr, Mn, Fe, Ni, Cu).

Circulating lipoprotein-associated phospholipase A2 in high-grade carotid stenosis: a new biomarker for predicting unstable plaque.

OBJECTIVE: To test plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with high-grade carotid stenosis according to plaque histology. METHODS: This cross-sectional single-centre study included patients with ≥70% North American Symptomatic Carotid Endarterectomy Trial (NASCET) carotid stenosis, who were treated surgically. Serum Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) were determined on the day of surgery. Histopathological analysis classified carotid plaque as stable or unstable, according to AHA classification. RESULTS: Of the 42 patients (mean age 70.4 ± 10.5 years; 67% men), neurological symptoms were present in 16 (38%). Unstable plaques were found in 23 (55%). Median plasma level of Lp-PLA2 was significantly higher in patients with unstable plaque compared to those with stable plaque (222.4 (174.9-437.5) interquartile range (IQR) 63.5 vs. 211.1 (174.9-270.6) IQR 37.2 ng ml(-1); p = 0.02). Moreover, median Lp-PLA2 level were higher in asymptomatic patients with unstable plaque (226.8 ng ml(-1) (174.9-437.5) IQR 76.8) vs. stable plaque (206.9 ng ml(-1) (174.9-270.6) IQR 33.7; p = 0.16). Logistic regression showed that only the neurological symptoms (OR = 30.9 (3.7-244.6); p < 0.001) and the plasma Lp-PLA2 level (OR = 1.7 (1.1-12.3); p = 0.03) were independently associated with unstable carotid plaque as defined by histology. CONCLUSIONS: This study showed that circulating Lp-PLA2 was increased in patients with high-grade carotid stenosis and unstable plaque. Lp-PLA2 may be a relevant biomarker to guide for invasive therapy in asymptomatic patients with carotid artery disease.

Microbial activities and trace element contents in an urban soil.

Soil biological properties are influenced by trace metals. The main sources of these pollutants in the urban areas are industrial plants, power stations, domestic heating systems and motor vehicles. The aim of this work was to evaluate, in relation to distance from urban roads, soil trace metal concentrations (Pb, Cu, Cr, Cd and V) and their influence on C-microbial biomass as well as on soil respiration and enzyme activities (phosphatase glucosidase, galactosidase, xylanase, cellulase, trealase, protease and invertase). The samplings were carried out at four sites, along a route that goes from Giannone Street to Passionisti Street, two heavily travelled roads at two different times of the year (spring and autumn). Heavy metal contents and microbial activities were highest at the sites near the roads. The highest values of microbial activities were found in the inner site; here, on the contrary, the lowest concentrations of heavy metals were measured. Significant and negative correlations were found between microbial activity and heavy metal contents.

Miocardiopatía hipertrófica asociada a corticoides orales en lactante afectada de hemangioma cutáneo / Hypertrophic myocardiopathy associated with oral corticosteroids in an infant with cutaneous hemangioma

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