The clonal evolution of two distinct T315I-positive BCR-ABL1 subclones in a Philadelphia-positive acute lymphoblastic leukemia failing multiple lines of therapy: a case report

BACKGROUND: The treatment of Philadelphia chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL) patients who harbor the T315I BCR-ABL1 mutation or who have two or more mutations in the same BCR-ABL1 molecule is particularly challenging since first and second-generation Tyrosine Kinase Inhibitors (TKIs) are ineffective. Ponatinib, blinatumomab, chemotherapy and transplant are the currently available options in these cases. CASE PRESENTATION: We here report the case of a young Ph+ ALL patient who relapsed on front-line dasatinib therapy because of two independent T315I-positive subclones, resulting from different nucleotide substitutions -one of whom never reported previously- and where additional mutant clones outgrew and persisted despite ponatinib, transplant, blinatumomab and conventional chemotherapy. Deep Sequencing (DS) was used to dissect the complexity of BCR-ABL1 kinase domain (KD) mutation status and follow the kinetics of different mutant clones across the sequential therapeutic approaches. CONCLUSIONS: This case presents several peculiar and remarkable aspects: i) distinct clones may acquire the same amino acid substitution via different nucleotide changes; ii) the T315I mutation may arise also from an 'act' to 'atc' codon change; iii) the strategy of temporarily replacing TKI therapy with chemo or immunotherapy, in order to remove the selective pressure and deselect aggressive mutant clones, cannot always be expected to be effective; iv) BCR-ABL1-mutated sub-clones may persist at very low levels (undetectable even by Deep Sequencing) for long time and then outcompete BCR-ABL1-unmutated ones becoming dominant even in the absence of any TKI selective pressure

Internal alignment and position resolution of the silicon tracker of DAMPE determined with orbit data

The DArk Matter Particle Explorer (DAMPE) is a space-borne particle detector designed to probe electrons and gamma-rays in the few GeV to 10 TeV energy range, as well as cosmic-ray proton and nuclei components between 10 GeV and 100 TeV. The silicon-tungsten tracker-converter is a crucial component of DAMPE. It allows the direction of incoming photons converting into electron-positron pairs to be estimated, and the trajectory and charge (Z) of cosmic-ray particles to be identified. It consists of 768 silicon micro-strip sensors assembled in 6 double layers with a total active area of 6.6 m$^2$. Silicon planes are interleaved with three layers of tungsten plates, resulting in about one radiation length of material in the tracker. Internal alignment parameters of the tracker have been determined on orbit, with non-showering protons and helium nuclei. We describe the alignment procedure and present the position resolution and alignment stability measurements

Dolor posoperatorio en craneotomía

In the postoperative period, 47% to 75% of the patients report some degree of pain. This study aimed to evaluate pain in the pre and postoperative period of patients submitted to craniotomy. This prospective research was carried out at the neurosurgery unit of a large Brazilian hospital. For a quantitative evaluation of pain, the verbal numeric 0 - 10 rating scale was used. Forty patients with a mean age of 36 years were evaluated. In the preoperative period, 34 (85%) patients indicated headache as the main cause of pain. In the postoperative period, 37 (93%) patients complained of pain while three (7%) reported absence of pain. Pain peaks were observed on the 2nd postoperative day, when 12 (32%) of the patients reported severe pain and 10 (27%) moderate pain. Absence of severe pain occurred after the 8th postoperative day. It was concluded that protocols of analgesia in craniotomy are needed, such as training nurses to better evaluate and handle pain.En el periodo postoperatorio, entre el 47% y el 75% de los pacientes relatan algún grado de dolor. Los objetivos de este trabajo fueron evaluar el dolor en el pre y postoperatorio de pacientes sometidos a craneotomía. Este estudio prospectivo fue realizado en la unidad de neurocirugía del Hospital São Paulo, Brasil. Para una evaluación cuantitativa del dolor se utilizó la escala numérica verbal graduada de 0 a 10. Fueron evaluados 40 pacientes con edad mediana de 36 años. En el preoperatorio 34 (85%) pacientes, reportaran cefalea como la principal causa del dolor. En el postoperatorio, 37 (93%) pacientes se quejaron de dolor, mientras 3 (7%) pacientes indicaron ausencia de dolor. El pico de dolor fue observado en el segundo día postoperatorio, cuando 12 (32%) pacientes reportaron dolor grave y 10 (27%) moderado. La ausencia de dolor grave ocurrió después del 8º día postoperatorio. Se concluyó que son necesarios protocolos de analgesia en craneotomía, tales como el entrenamiento de enfermeros para mejor evaluar y manejar el dolor.No pós-operatório, 47 a 75% dos pacientes relatam algum grau de dor. O objetivo deste trabalho foi avaliar a dor no pré e pós-operatório de pacientes submetidos a craniotomia. Estudo prospectivo, realizado na unidade de neurocirurgia do Hospital São Paulo. Para avaliação quantitativa de dor, foi utilizada a escala numérica verbal, graduada de 0 a 10. Foram avaliados 40 pacientes, com idade mediana de 36 anos. No pré-operatório, 34 (85%) pacientes relataram cefaléia como a principal causa de dor. No pós-operatório, 37 (93%) pacientes queixaram-se de dor e 3 (7%) pacientes referiram ausência de dor. O pico da dor foi observado no 2º pós-operatório, quando 16 (40%) dos pacientes referiram dor intensa e 11 (28%) queixaram-se de dor moderada. Ausência de dor intensa ocorreu após 6º pós-operatório. Concluí-se que há necessidade de protocolos de analgesia em craniotomia, como treinamento para os enfermeiros para melhor avaliação e manejo da dor.Hospital Israelita Albert EinsteinUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Proton energy spectrum with the DAMPE experiment

The DAMPE (DArk Matter Particle Explorer) experiment, in orbit since December 17th 2015, is a space mission whose main purpose is the detection of cosmic electrons and photons up to energies of 10 TeV, in order to identify possible evidence of Dark Matter in their spectra. Furthermore it aims to measure the spectra and the elemental composition of the galactic cosmic rays nuclei up to the energy of hundreds of TeV. The proton analysis and the flux with kinetic energy ranging from 50 GeV up to 100 TeV, at the end of two years of data taking, will be presented and discussed