Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study.

Purpose: Off-label use of vemurafenib (VMF) to treat mutation-positive, refractory, childhood Langerhans cell histiocytosis (LCH) was evaluated.

Patients And Methods: Fifty-four patients from 12 countries took VMF 20 mg/kg/d. They were classified according to risk organ involvement: liver, spleen, and/or blood cytopenia.

[Proliferative activity of paravasal connective tissue cells in the age aspect.].

The aim of the study was to investigate the age-related variability of the proliferative activity of fibroblasts of the paravasal connective tissue of the hollow and parenchymal organs of men corpses of the first period of mature age, elderly and senile age by detecting the expression of the Ki-67 protein (MIB-1 clone) and calculating the proliferation index. The results showed that in the first period of mature age, the proliferation index is almost at the same level in the paravasal tissue cells of the parenchymal and hollow organs of the digestive tract, while the fibroblasts of the paravasal tissue of the heart have the lowest proliferation activity among all the organs studied. With age, the intensity of cell proliferation decreases, moreover, at the age of more than 75 years, a distinct organ specificity is revealed.

[Age changes in connective tissue structures of the stomach.].

The study of paravasal connective tissue of the stomach was carried out on the preparations of 80 men corpses of three age groups: the first period of adulthood (n=20), the elderly (n=30) and senile (n=30) ages. With the help of standard histological and histochemical methods, the features of the age-related variability of the fiber composition were established; the level of apoptosis and proliferation in fibroblasts has been investigated with the help of immunohistochemical methods. The regularities of the structural organization of the paravasal connective tissue of the stomach during the period of biological stability (the first period of adulthood), as well as its age transformations at the stages of postnatal ontogeny (in the older age groups), were revealed.

[Age-related changes Kernogan`s index of venous vessels hollow and parenchymatous organs at stages of a postnatal ontogenesis].

Kernogan`s index determination of hollow and parenchymatous organs' venous vessels was conducted on 80 men corpses of the three age groups. Average age of the investigated men corpses of the mature period is 27,8±4,2 years, elderly - 67,8±3,7 years, senile - 81,9±4,5 years. The age variability transformation of venous vessels bandwidth of lungs, kidneys, heart, stomach and ileum were obligate.

[Paravasal connective tissue of the in-wall blood vessels of the heart during aging].

The structural organization of the paravasal connective tissue of the in-wall myocardial blood vessels in the stages of postnatal ontogenesis was studied. The study was carried out on preparations of the heart 80 corpses of men in three age groups (the first period of adulthood (n = 20) and elderly (n = 30) and old (n = 30) ages.) The peculiarities of the structure as well as qualitative and quantitative transformation of fibrous component of the paravasal connective tissue in each age period were revealed.