Tyrosine Kinase Inhibitor Resistance in Patients with Chronic Myeloid Leukemia: A 10-Year Study of BCR-ABL Gene Mutation Profile in Russia (2006–2016)

Background. Kinase domain mutations of BCR-ABL gene is the most common cause of tyrosine kinase inhibitor resistance. Aim. To present the data on prognostic value of BCR-ABL mutation burden in Russian patients over the last 10 years. Materials & Methods. The study included 1885 chronic myeloid leukemia (CML) patients with tyrosine kinase inhibitor resistance who were followed up from 2006 to 2016. BCR-ABL point mutations in mRNA samples were analyzed by means of polymerase chain reaction and subsequent Sanger sequencing. Results. In 1257 CML patients with signs of tyrosine kinase inhibitor resistance BCR-ABL expression level was > 1 %. BCR–ABL mutations were detected in 31.8 % of patients. Total mutation count was 467 (70 mutation types). Total count of patients with mutation-associated tyrosine kinase inhibitor resistance decreased from 36.6 % (2006–2008) to 24.95 % (2013–2016) and to marked decrease of 23.12 % in 2014. Detection rate of imatinib-resistant mutations and F359V mutation was shown to decrease within the period from 2010–2011 to 2014–2015. F317L level, which is responsible for dasatinib resistance, considerably increased in 2015. T315I frequency was the highest in 2014, afterwards it was gradually decreasing. Mutation-associated resistance rates varied by region of the Russian Federation. Conclusion. The analysis of trends of mutation incidence in patients with CML can be of extreme significance in long-term prognosis of resistance development and in improvement of treatment planning

Протокол функционального обследования аноректальной зоны и классификация нарушений: международный консенсус и Российские рекомендации

This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high-resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. Aim to provide information about methods of diagnosis and new classification of functional anorectal disorders to a wide range of specialists general practitioners, therapists, gastroenterologists, coloproctologists all who face the manifestations of these diseases in everyday practice and determine the diagnostic and therapeutic algorithm. Current paper provides agreed statements of IAPWG Consensus and comments (in italics) of Russian experts on real-world practice, mainly on methodology of examination. These comments in no way intended to detract from the provisions agreed by the international group of experts. We hope that these comments will help to improve the quality of examination based on the systematization of local experience with the use of the methods discussed and the results obtained. Key recommendations: the International Anorectal Physiology Working Group protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia

Suppression in Pb-Pb Collisions at the LHC.

The production of the ψ(2S) charmonium state was measured with ALICE in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV, in the dimuon decay channel. A significant signal was observed for the first time at LHC energies down to zero transverse momentum, at forward rapidity (2.5<y<4). The measurement of the ratio of the inclusive production cross sections of the ψ(2S) and J/ψ resonances is reported as a function of the centrality of the collisions and of transverse momentum, in the region p_{T}<12  GeV/c. The results are compared with the corresponding measurements in pp collisions, by forming the double ratio [σ^{ψ(2S)}/σ^{J/ψ}]_{Pb-Pb}/[σ^{ψ(2S)}/σ^{J/ψ}]_{pp}. It is found that in Pb-Pb collisions the ψ(2S) is suppressed by a factor of ∼2 with respect to the J/ψ. The ψ(2S) nuclear modification factor R_{AA} was also obtained as a function of both centrality and p_{T}. The results show that the ψ(2S) resonance yield is strongly suppressed in Pb-Pb collisions, by a factor of up to ∼3 with respect to pp. Comparisons of cross section ratios with previous Super Proton Synchrotron findings by the NA50 experiment and of R_{AA} with higher-p_{T} results at LHC energy are also reported. These results and the corresponding comparisons with calculations of transport and statistical models address questions on the presence and properties of charmonium states in the quark-gluon plasma formed in nuclear collisions at the LHC