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.

[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.