[Hypofractionated radiotherapy for glioblastoma: changing the radiation treatment paradigm]. / Gipofraktsionirovanie pri glioblastomakh: izmenenie paradigmy luchevogo lecheniia.

Hypofractionation has the dual advantage of increased cell death with a higher dose per fraction and a reduced effect of accelerated tumor cell repopulation due to a shorter overall treatment time. However, the potential advantage may be offset by increased toxicity in the late-responding neural tissues. Recently, investigators have attempted delivering radical doses of HFRT by escalating the dose in the immediate vicinity of the enhancing tumor and postoperative surgical cavity and reported reasonable outcomes with acceptable toxicity levels. Three different studies of high-dose HFRT have reported on the paradoxical phenomenon of improved survival in patients developing radiation necrosis at the primary tumor site. The toxicity criteria of RTOG and EORTC have defined clinically or radiographically suspected radionecrosis as Grade 4 toxicity. However, most patients diagnosed with radiation necrosis in the above studies remained asymptomatic. Furthermore, the probable association with improved survival would strongly argue against adopting a blind approach for classifying radiation necrosis as Grade 4 toxicity. The data emerging from the above studies is encouraging and strongly argues for further research. However, the majority of these studies are predominantly retrospective or relatively small single-arm prospective series that add little to the overall quality of evidence. Notwithstanding the above limitations, HFRT appears to be a safe and feasible strategy for glioblastoma patients.

[A possible association of fatal pneumonia with mutations of pandemic influenza A/H1N1 sw1 virus in the receptor-binding site of the HA1 subunit].

The paper gives the results of sequence analysis of 150 positive samples in real-time RT-PCR, including 47 autopsy materials from patients (including 10 pregnant women), who died from fatal pneumonia mainly in November-December 2009, in whom the lifetime etiological diagnosis had not been made and hence no early etiotropic therapy performed. 70% of the primary materials from the deceased patients were found to have pandemic influenza A(H1N1) v mutants in the lung tissue with D222G (15%), D222N (15%), D222E (2%) substitutions, as well as a mixture of mutants (38%). Nasopharyngeal lavages from 3 Chukotka deceased patients exhibited only consensus (nonmutant) D222 virus variants; there was a mixture of consensus and mutant virus variants in the trachea and a mixture of mutant ones in the lung. Preliminary data from the study of the interaction of the hemagglutinin of two strains having D222G and D222N mutations with 9 oligosaccharides imitating the variants of cell receptors for influenza A virus suggest that there is a double receptor specificity for alpha2'-3' and alpha2'-6'-sialosides with a preponderance of alpha2'-3'-specificity. Further spread of the mutants that have acquired a high virulence and preserved their capacity for the respiratory route of human infection may lead to the situation similar to that seen in the 1918-1919 pandemic. Another scenario for evolution of the virus is to preserve its receptor specificity for alpha2'-3'-sialosides and high virulence with losses of alpha2'-6' specificity and capacity for aerosol transmission, by damping the pandemic.

[Detection of amino acid substitutions of asparaginic acid for glycine and asparagine at the receptor-binding site of hemagglutinin in the variants of pandemic influenza A/H1N1 virus from patients with fatal outcome and moderate form of the disease].

The paper analyzes the amino acid sequence of the receptor-binding site of hemagglutinin (HA) in the variants of pandemic influenza A/H1N1 swl from 18 patients with moderate (n=1) and fatal (n=17) forms of the disease in 2009. Nine samples contained asparaginic acid at position 222 of HA1 (D). This site exhibited mutations in 9 samples: D222G (n=3), D222N (n=3), and D222G/D222N (n=3). In one patient with the moderate form of the disease, D222G mutation was revealed after the second passage in the developing chick embryos; this mutation was not found in the primary sample from the patient. The findings suggest the mutant variants of the virus start to circulate among the population, which requires, firstly, continuation of molecular virological monitoring of the pandemic situation and, secondly, further study of the impact of amino acid substitutions at the receptor-binding site of HA1 on the increased virulence of influenza A virus.