Prognosis assessment of early-stage chronic lymphocytic leukemia: Are we ready to predict clinical evolution without a crystal ball?

On behalf ofGrupo Español de Leucemia Linfática Crónica and Grupo Cooperativo Español de Citogenética Hematológica.[Background]: The discovery of new biologic variables with high prognostic effect has been accompanied by the emergence of different prognostic indexes (PIs) to assess the time to first treatment in patients with early-stage (Binet A) chronic lymphocytic leukemia (CLL). The present study compared the prognostic value of 5 PIs: CLL international prognostic index (CLL-IPI), Barcelona-Brno, international prognostic score-A (IPS-A), CLL-01, and a tailored approach.[Patients and Methods]: We applied the 5 PIs to a cohort of 428 unselected patients with Binet A CLL from a multicenter Spanish database with clinical and biologic information available. The predictive value of the scores was assessed using Harrell’s concordance index (C index) and area under the receiver operating characteristic curve (AUC).[Results]: We found a significant association between time to first treatment and risk subgroups for all 5 PIs used. The most accurate PI was the IPS-A (C-index, 0.72; AUC, 0.76), closely followed by CLL-01 (C-index, 0.69; AUC, 0.70), CLL-IPI (C-index, 0.69; AUC, 0.69), Barcelona-Brno (C-index, 0.67; AUC, 0.69), and the tailored approach (C-index, 0.61 and 0.58; AUC, 0.58 and 0.54).[Conclusions]: The concordance between the PIs was low (44%), suggesting that although all these PIs improve clinical staging and help physicians in routine clinical practice, it will be necessary to harmonize larger cohorts of patients to define the best PI for treatment decision-making in the real world.The present study was supported by the Spanish Fondo de Investigaciones Sanitarias (grants PI15/01471 and PI18/01500), Instituto de Salud Carlos III, European Regional Development Fund (Una manera de hacer Europa), Consejería de Educación, Junta de Castilla y León (grant SA271P18), Proyectos de Investigación del SACYL (grants GRS1847/A/18 and GRS1653/A17), Fundación Memoria Don Samuel Solórzano Barruso (grant FS/23-2018), Red Temática de Investigación Cooperativa en Cáncer (grant RD12/0036/0069), Centro de Investigación Biomédica en Red de Cáncer (grant CIBERONC CB16/12/00233), and Synthetic Lethality for Personalized Therapy-based Stratification in Acute Leukemia (grant ERAPERMED2018-275); and Instituto de Salud Carlos III (grant AC18/00093). M.H.S. holds a Sara Borrell postdoctoral contract (CD19/00222) from the Spanish Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, European Regional Development Fund (El Fondo Social Europeo invierte en tu future). A.E.R.V. is supported by a research grant from the Fundación Española de Hematología y Hemoterapia. M.Q.Á. is fully supported by the Ayuda predoctoral de la Junta de Castilla y León from the Fondo Social Europeo (PhD scholarship JCYL EDU/529/2017). C.P.C. is a recipient of a PFIS grant (FI19/00191) from Instituto de Salud Carlos III, cofounded by Fondo Social Europeo (El Fondo Social Europeo invierte en tu future).Peer reviewe

Encapsulation of <i>Lacticaseibacillus rhamnosus</i> GG: Probiotic Survival, In Vitro Digestion and Viability in Apple Juice and Yogurt

This study was aimed to prepare and characterize capsules loaded with Lacticaseibacillus rhamnosus GG (LGG), evaluating cell viability under gastrointestinal in vitro conditions and during storage in yogurt and apple juice, an alternative to traditional probiotic foods for people who are lactose intolerant. The capsules were prepared by ionic gelation, with an emulsification process as pretreatment. Cell viability of encapsulated LGG was evaluated after two different homogenization processes: magnetic stirring (AM) and Ultraturrax® homogenizer (UT). The system with the best relationship between viability and morphology was UT, which produced a viability of 85.80%. During in vitro evaluation, the capsules provided higher protection than free cells, up to 100% of cell viability. The morphology of capsules of both systems displayed a continuous and homogeneous surface. The cell viability of the encapsulated probiotics added in apple juice stored for 22 days at 4 °C was 86.16% for AM and 100% for UT, while the viability of free cells was 80.50%. In natural yogurt, the cell viability of the probiotics encapsulated stored 30 days at 4 °C was 100% for AM, 100% for UT, and 92.68% for free cells. This study suggests an alternative to preserve probiotic bacteria in a potential functional food

Encapsulation of Lacticaseibacillus rhamnosus GG: Probiotic Survival, In Vitro Digestion and Viability in Apple Juice and Yogurt

This study was aimed to prepare and characterize capsules loaded with Lacticaseibacillus rhamnosus GG (LGG), evaluating cell viability under gastrointestinal in vitro conditions and during storage in yogurt and apple juice, an alternative to traditional probiotic foods for people who are lactose intolerant. The capsules were prepared by ionic gelation, with an emulsification process as pretreatment. Cell viability of encapsulated LGG was evaluated after two different homogenization processes: magnetic stirring (AM) and Ultraturrax&reg; homogenizer (UT). The system with the best relationship between viability and morphology was UT, which produced a viability of 85.80%. During in vitro evaluation, the capsules provided higher protection than free cells, up to 100% of cell viability. The morphology of capsules of both systems displayed a continuous and homogeneous surface. The cell viability of the encapsulated probiotics added in apple juice stored for 22 days at 4 &deg;C was 86.16% for AM and 100% for UT, while the viability of free cells was 80.50%. In natural yogurt, the cell viability of the probiotics encapsulated stored 30 days at 4 &deg;C was 100% for AM, 100% for UT, and 92.68% for free cells. This study suggests an alternative to preserve probiotic bacteria in a potential functional food

Encapsulation of Lactobacillus gasseri: Characterization, Probiotic Survival, In Vitro Evaluation and Viability in Apple Juice

The development of functional foods containing probiotic bacteria has become increasingly relevant to improve and maintain health. However, this is often limited to dairy food matrices given the complexity involved in maintaining a stable system together with high microbial viability in matrices such as juices. The objective of this study was to develop and characterize sodium alginate capsules loaded with Lactobacillus gasseri ATCC&reg; 19992 &trade; (LG). Cell viability under in vitro gastrointestinal conditions and during storage in apple juice were evaluated. The capsules were prepared by ionic gelation and an emulsification process was performed as pretreatment using two homogenization methods: magnetic stirring (AM) and Ultraturrax&reg; rotor-stator homogenizer (UT). Cell viability after encapsulation was similar in the two processes: 65%. At the end of the in vitro gastrointestinal evaluation, the non-encapsulated probiotic cells did not show any viability, while the AM system was able to retain 100% of its viability and the UT retained 79.14%. The morphology of the capsules consisted of a continuous and homogeneous surface. Cell viability of LG encapsulated in apple juice stored at 4 &deg;C for 21 days was 77% for AM, 55.43% for UT, and 63.10% for free LG

Intervención psicológica como parte del tratamiento integral de pacientes con insuficiencia cardíaca: Efecto sobre la capacidad funcional

El objetivo del presente trabajo fue investigar el efecto de una intervención psicológica cognitivo-conductual en la capacidad funcional de los pacientes con insuficiencia cardiaca, medida a través de la prueba de caminata de seis minutos. Participaron 53 pacientes, clases funcionales I y II, asignados aleatoriamente a: 1) grupo control (tratamiento médico usual, n=27, edad media 61.07±15.96, 55.6% hombres), o 2) grupo experimental (tratamiento médico usual e intervención psicológica, n=26, edad media 58.42±16.42, 65.4% mujeres). Mediante la prueba de caminata de seis minutos se evalúo la distancia recorrida en metros, el nivel de cansancio físico y el nivel de esfuerzo reportado en la escala de Borg. Las evaluaciones se realizaron antes y al final del programa de intervención, además de un seguimiento a tres meses. El programa de intervención psicológica incluyó psicoeducación, respiración diafragmática, relajación muscular progresiva y entrenamiento en solución de problemas, en cuatro sesiones de 90 minutos cada una, diferidas semanalmente. Los resultados muestran que el grupo experimental incrementó (p=0.00) la distancia recorrida y disminuyó el nivel de cansancio físico (p=0.02) y nivel de esfuerzo reportados (ns), lo cual se traduce en un mejor pronóstico. El grupo control no mostró cambios significativos. Se concluye que la intervención propuesta se adapta a las necesidades de la población con un efecto positivo en su condición de salud, por lo que se sugiere la integración de equipos interdisciplinarios que incluyan programas de intervención psicológica para mejorar la salud cardiovascular y la calidad de vida de los pacientes

Association of Cytogenetics Aberrations and <i>IGHV</i> Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting

Immunoglobulin heavy chain variable (IGHV) region mutations, TP53 mutation, fluorescence in situ hybridization (FISH), and cytogenetic analysis are the most important prognostic biomarkers used in chronic lymphocytic leukemia (CLL) patients in our daily practice. In real-life environment, there are scarce studies that analyze the correlation of these factors with outcome, mainly referred to time to first treatment (TTFT) and overall survival (OS). This study aimed to typify IGHV mutation status, family usage, FISH aberrations, and complex karyotype (CK) and to analyze the prognostic impact in TTFT and OS in retrospective study of 375 CLL patients from a Spanish cohort. We found unmutated CLL (U-CLL) was associated with more aggressive disease, shorter TTFT (48 vs. 133 months, p < 0.0001), and shorter OS (112 vs. 246 months, p < 0.0001) than the mutated CLL. IGHV3 was the most frequently used IGHV family (46%), followed by IGHV1 (30%) and IGHV4 (16%). IGHV5-51 and IGHV1-69 subfamilies were associated with poor prognosis, while IGHV4 and IGHV2 showed the best outcomes. The prevalence of CK was 15% and was significantly associated with U-CLL. In the multivariable analysis, IGHV2 gene usage and del13q were associated with longer TTFT, while VH1-02, +12, del11q, del17p, and U-CLL with shorter TTFT. Moreover, VH1-69 usage, del11q, del17p, and U-CLL were significantly associated with shorter OS. A comprehensive analysis of genetic prognostic factors provides a more precise information on the outcome of CLL patients. In addition to FISH cytogenetic aberrations, IGHV and TP53 mutations, IGHV gene families, and CK information could help clinicians in the decision-making process

Nutritional Ecology

This paper is in closed access

Compilación de Proyectos de Investigacion de 1984-2002

Instituto Politecnico Nacional. UPIICS