Is Hematopoietic Clonality of Indetermined Potential a Risk Factor for Pulmonary Embolism?

Background Unprovoked pulmonary embolism (uPE) is a severe and frequent condition. Identification of new risk factors is mandatory to identify patients that would benefit from a long-term treatment. Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the acquisition of somatic mutations that drive clonal expansion in the absence of cytopenia. Its prevalence is estimated of 5% in the population above 65 years. Since inflammation and endothelial dysfunction may share a pathophysiological pathway(1), we hypothesized that CHIP, may be a risk factor for uPE. Methods We conducted a pilot retrospective observational study. Patients with iPE between 18 to 65 years old were included. PE was considered as unprovoked, when no transient nor persistant risk factor was present and when thrombophilia testing was negative. We excluded documented atherosclerosis, personal or familial history of VTE and presence of cytopenias. CHIP proportion in uPE patients were analyzed using next generation sequencing of the coding sequence of a custom panel composed by DNMT3A, ASXL1, SF3B1, TET2 and TP 53 . Results Upon 61 patients with uPE consecutively included, a total of 19 somatic mutations were found in 12 patients (20%) IC95% [10 - 20]. 15 mutations were found in DNMT3A gene, 3 in ASXL1 and one in TET2 . There was no diference in terms of age, PE location, DVT presence and risk stratification in CHIP carriers and non carriers. Conclusion We report for the first time, the presence of high rates of CHIP in patients presenting with uPE. Thus, CHIP may be a new risk factor for VTE. These results need to be confirmed in an ongoing prospective case-control study including more patients and using a more diverse gene panel to better determine CHIP incidence in uPE.

Spatial and temporal variability of (7)Be and (210)Pb wet deposition during four successive monsoon storms in a catchment of northern Laos.

Fallout radionuclides (7)Be and (210)Pb have been identified as potentially relevant temporal tracers for studying soil particles dynamics (surface vs. subsurface sources contribution; remobilization of in-channel sediment) during erosive events in river catchments. An increasing number of studies compared (7)Be: (210)Pb activity ratio in rainwater and sediment to estimate percentages of freshly eroded particles. However, the lack of data regarding the spatial and temporal variability of radionuclide wet deposition during individual storms has been identified as one of the main gaps in these estimates. In order to determine these key parameters, rainwater samples were collected at three stations during four storms that occurred at the beginning of the monsoon (June 2013) in the Houay Xon mountainous catchment in northern Laos. Rainwater (7)Be and (210)Pb activities measured using very low background hyperpure Germanium detectors ranged from 0.05 to 1.72 Bq L(-1) and 0.02 to 0.26 Bq L(-1), respectively. Water δ(18)O were determined on the same samples. Total rainfall amount of the four sampled storms ranged from 4.8 to 26.4 mm (51 mm in total) at the time-fractionated collection point. Corresponding cumulative (7)Be and (210)Pb wet depositions during the sampling period were 17.6 and 2.9 Bq m(-2), respectively. The (7)Be: (210)Pb activity ratio varied (1) in space from 6 to 9 for daily deposition and (2) in time from 3 to 12 for samples successively collected. Intra-event evolution of rainwater (7)Be and (210)Pb activities as well as δ(18)O highlighted the progressive depletion of local infra-cloud atmosphere radionuclide stock with time (washout), which remains consistent with a Raleigh-type distillation process for water vapour. Intra-storm ratio increasing with time showed the increasing contribution of rainout scavenging. Implications of such variability for soil particle labelling and erosion studies are briefly discussed and recommendations are formulated for the collection of rainwater signature in studies based on the (7)Be: (210)Pb ratio method, especially in tropical areas under high erosive pressure.

Remanence of lead pollution in an urban river system: a multi-scale temporal and spatial study in the Seine River basin, France.

Total lead (Pb) concentration and Pb isotopic ratio ((206)Pb/(20)7Pb) were determined in 140 samples from the Seine River basin (France), covering a period of time from 1945 to 2011 and including bed sediments (bulk and size fractionated samples), suspended particulate matter (SPM), sediment cores, and combined sewer overflow (CSO) particulate matter to constrain the spatial and temporal variability of the lead sources at the scale of the contaminated Seine River basin. A focus on the Orge River subcatchment, which exhibits a contrasted land-use pattern, allows documenting the relation between hydrodynamics, urbanization, and contamination sources. The study reveals that the Pb contamination due to leaded gasoline that peaked in the 1980s has a very limited impact in the river nowadays. In the upstream Seine River, the isotopic ratio analysis suggests a pervasive contamination which origin (coal combustion and/or gasoline lead) should be clarified. The current SPM contamination trend follows the urbanization/industrialization spatial trend. Downstream of Paris, the lead from historical use originating from the Rio Tinto mine, Spain ((206)Pb/(207)Pb=1.1634 ± 0.0001) is the major Pb source. The analysis of the bed sediments (bulk and grain size fractionated) highlights the diversity of the anthropogenic lead sources in relation with the diversity of the human activities that occurred in this basin over the years. The "urban" source, defined by waste waters including the CSO samples ((206)Pb/(207)Pb=1.157 ± 0.003), results of a thorough mixing of leaded gasoline with "historical" lead over the years. Finally, a contamination mixing scheme related to hydrodynamics is proposed.

[Intramuscular premedication with midazolam in infants and children]. / La prémédication intramusculaire au midazolam chez le nourrisson et l'enfant.

The useful intramuscular premedication dose of midazolam was determined in 100 children divided up in three age groups: one month to three years, 3 to 10 years, 10 to 15 years. All biometric parameters were normal for the age, and comparable between similar age groups. Haemodynamic and respiratory parameters were not altered by the premedication. The reduction in anxiety, as assessed by the child's behaviour, was good or excellent in more than 85% of cases from all age groups; it was proportional to the dose used. The doses that had, for equivalent reductions in anxiety as assessed by the chi-square test, the least hypnotic effect, were: 0.5 mg X kg-1 before three years of age, 0.4 mg X kg-1 for the 3 to 10 yr olds, and 0.25 mg X kg-1 for the 10 to 15 yr olds. This fall in dose with age, quite usual in paediatrics, was not unexpected. The level of consciousness, one hour after surgery, was always normal. No undesirable side-effect was observed. These results, together with its physical, chemical and pharmacodynamic characteristics, make midazolam a choice drug for intramuscular premedication in children, with a foreseeable use in day-care anaesthesia. The unexpected finding of an age-dependent dissociation between the reduction in anxiety and the hypnotic effect is discussed in the light of a study carried out in the adult and recent data from the literature.

[A case of intra- and extracranial development of a craniofacial teratoma. Excision during the neonatal period through a mixed cranio-facial approach (author's transl)]. / Tératome cranio-facial à développement mixte intra- et extra-crânien. Cure chirurgicale en un temps par intervention cranio-faciale.

A newborn infant was found to have a laterocervical swelling invading the floor of the mouth. Exploration of the mass revealed that there was invasion of the left side of the soft palate and, more particularly, a prominence in the temporal fossa causing an obvious cranio-facial asymmetry. Radiological and neuroradiological investigations demonstrated the presence of a tumor destroying the greater wing of the sphenoid, invading the left side of the temporal fossa, extending into the pterygomaxillary fossa up to the soft palate, and finally appearing exteriorly in the sub-maxillary region. Excision was carried out in the neonatal period because of the poor tolerance from the neurological point of view. A wide cranio-facial approach was first employed, enabling resection of the point of the temporal lobe, clogging of the cranial base, and excision as one piece of the complete palatocervical extension of the tumor. Follow-up one year later showed that the child possessed excellent neurological development and there was no sign of recurrence of the mass. A review of the published literature showed the extremely rare nature of this type of localization of cervicofacial teratomas (5 other cases have been reported). The surgical procedures and the problems encountered are discussed as well as the indications for excision, based on results obtained in this case and those previously reported. The etiology and anatomy are also reviewed in order to establish their true significance in the case of congenital cranio-facial tumors.