Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV.

The prognostic relevance of additional cytogenetic findings at diagnosis of chronic myeloid leukemia (CML) is unclear. The impact of additional cytogenetic findings at diagnosis on time to complete cytogenetic (CCR) and major molecular remission (MMR) and progression-free (PFS) and overall survival (OS) was analyzed using data from 1151 Philadelphia chromosome-positive (Ph(+)) CML patients randomized to the German CML Study IV. At diagnosis, 1003 of 1151 patients (87%) had standard t(9;22)(q34;q11) only, 69 patients (6.0%) had variant t(v;22), and 79 (6.9%) additional cytogenetic aberrations (ACAs). Of these, 38 patients (3.3%) lacked the Y chromosome (-Y) and 41 patients (3.6%) had ACAs except -Y; 16 of these (1.4%) were major route (second Philadelphia [Ph] chromosome, trisomy 8, isochromosome 17q, or trisomy 19) and 25 minor route (all other) ACAs. After a median observation time of 5.3 years for patients with t(9;22), t(v;22), -Y, minor- and major-route ACAs, the 5-year PFS was 90%, 81%, 88%, 96%, and 50%, and the 5-year OS was 92%, 87%, 91%, 96%, and 53%, respectively. In patients with major-route ACAs, the times to CCR and MMR were longer and PFS and OS were shorter (P < .001) than in patients with standard t(9;22). We conclude that major-route ACAs at diagnosis are associated with a negative impact on survival and signify progression to the accelerated phase and blast crisis.

Todo tipo de relacionamento consumidor-marca é eficiente?

O objetivo neste estudo foi investigar a existência de diferentes perfis de relacionamento consumidor-marca e sua respectiva eficiência na relação comercial. Três construtos da teoria de relacionamento com marcas foram avaliados: autoconexão, intimidade e interdependência com a marca. Foi realizado um survey com 441 casos. Os dados foram analisados por técnicas de cluster, fatorial e ANOVA. Três diferentes perfis foram encontrados: o relacionamento por inércia (RI), o qual sugere uma relação superficial e com menor poder de diferenciação sobre a marca; o relacionamento moderado (RM), o qual registrou avaliações intermediárias em todas as variáveis; o relacionamento verdadeiro (RV), o qual demonstra maior proximidade e conexão com a marca. Para verificar a eficiência desses tipos, foram avaliados os índices de satisfação, confiança, comprometimento e lealdade. Consumidores do tipo RI tendem a trocar de marca tão logo percebam vantagens maiores em outros concorrentes. Já os RM demonstram certa tendência de atitudes positivas em relação à marca, dependendo de seu contexto e oferta. O grupo RV demonstra maior tendência à continuidade do relacionamento. Do ponto de vista gerencial, perceber diferentes intensidades de relacionamento permite reconhecer que nem todo relacionamento é eficiente.

Impact of Balanced or Unbalanced Karyotype At Diagnosis On Prognosis of CML: Long-Term Observation From 1346 Patients of the Randomized CML Study IV

Introduction: Acquired genetic instability in chronic myeloid leukemia (CML) as a consequence of the translocation t(9;22)(q34;q11) and the resulting BCR-ABL fusion causes the continuous acquisition of additional chromosomal aberrations and mutations and thereby progression to accelerated phase (AP) and blast crisis (BC). At least 10% of patients in chronic phase (CP) CML show additional alterations at diagnosis. This proportion rises during the course of the disease up to 80% in BC. Acquisition of chromosomal changes during treatment is considered as a poor prognostic indicator, whereas the impact of chromosomal aberrations at diagnosis depends on their type. Patients with major route additional chromosomal alterations (major ACA: +8, i(17)(q10), +19, +der(22)t(9;22)(q34;q11) have a worse outcome whereas patients with minor route ACA show no difference in overall survival (OS) and progression-free survival (PFS) compared to patients with the standard translocation, a variant translocation or the loss of the Y chromosome (Fabarius et al., Blood 2011). However, the impact of balanced vs. unbalanced (gains or losses of chromosomes or chromosomal material) karyotypes at diagnosis on prognosis of CML is not clear yet. Patients and methods: Clinical and cytogenetic data of 1346 evaluable out of 1544 patients with Philadelphia and BCR-ABL positive CP CML randomized until December 2011 to the German CML-Study IV, a randomized 5-arm trial to optimize imatinib therapy by combination, or dose escalation and stem cell transplantation were investigated. There were 540 females (40%) and 806 males (60%). Median age was 53 years (range, 16-88). The impact of additional cytogenetic aberrations in combination with an unbalanced or balanced karyotype at diagnosis on time to complete cytogenetic and major molecular remission (CCR, MMR), PFS and OS was investigated. Results: At diagnosis 1174/1346 patients (87%) had the standard t(9;22)(q34;q11) only and 75 patients (6%) had a variant t(v;22). In 64 of 75 patients with t(v;22), only one further chromosome was involved in the translocation; In 8 patients two, in 2 patients three, and in one patient four further chromosomes were involved. Ninety seven patients (7%) had additional cytogenetic aberrations. Of these, 44 patients (3%) lacked the Y chromosome (-Y) and 53 patients (4%) had major or minor ACA. Thirty six of the 53 patients (2.7%) had an unbalanced karyotype (including all patients with major route ACA and patients with other unbalanced alterations like -X, del(1)(q21), del(5)(q11q14), +10, t(15;17)(p10;p10), -21), and 17 (1.3%) a balanced karyotype with reciprocal translocations [e.g. t(1;21); t(2;16); t(3;12); t(4;6); t(5;8); t(15;20)]. After a median observation time of 5.6 years for patients with t(9;22), t(v;22), -Y, balanced and unbalanced karyotype with ACA median times to CCR were 1.05, 1.05, 1.03, 2.58 and 1.51 years, to MMR 1.31, 1.51, 1.65, 2.97 and 2.07 years. Time to CCR and MMR was longer in patients with balanced karyotypes (data statistically not significant). 5-year PFS was 89%, 78%, 87%, 94% and 69% and 5-year OS 91%, 87%, 89%, 100% and 73%, respectively. In CML patients with unbalanced karyotype PFS (p<0.001) and OS (p<0.001) were shorter than in patients with standard translocation (or balanced karyotype; p<0.04 and p<0.07, respectively). Conclusion: We conclude that the prognostic impact of additional cytogenetic alterations at diagnosis of CML is heterogeneous and consideration of their types may be important. Not only patients with major route ACA at diagnosis of CML but also patients with unbalanced karyotypes identify a group of patients with shorter PFS and OS as compared to all other patients. Therefore, different therapeutic options such as intensive therapy with the most potent tyrosine kinase inhibitors or stem cell transplantation are required.

Software para la representación gráfica a la solución de ruteo y carga de vehículos en algoritmo de tipo 2L-CVRP

El siguiente artículo presenta el trabajo realizado en la creación de una aplicación de software libre que representa gráficamente las rutas generadas y la distribución de los elementos transportados en el interior de un vehículo de carga.

Musée de l'histoire du costume, France, Henri IV [32 rue Beaujon, Hôtel de Madrazo, Paris, 8e arrondissement, ouvert au public le 24 janvier 1920] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57824

Avaliação de dois esquemas de monitorização domiciliar em pacientes com diabetes mellitus do tipo 1

O estudo teve por objetivo avaliar a efetividade de esquemas de monitorização domiciliar sangüíneo e urinário, na obtenção de adequado controle glicêmico, em pacientes com diabetes mellitus do tipo 1, em regime quinzenal de ajuste terapêutico; durante 6 meses de participação em grupos educativos. A amostra foi de 34 pacientes divididos em dois grupos. Os pacientes do grupo A realizaram monitorização domiciliar da glicemia capilar 1 vez ao dia e os do grupo B realizaram monitorização domiciliar da glicosúria 1 vez ao dia, conforme esquemas preconizados. Estes esquemas possibilitaram construção de perfis e de ajustes terapêuticos. Os resultados mostraram que o uso sistemático dos testes domiciliares sangúíneos e urinários da forma prescrita, não proporcionou melhora significante no controle metabólico em nenhum dos dois grupos. Entretanto, favoreceu o processo educativo e possibilitou reflexões sobre a necessidade de intensificação da monitorização glicêmica.