Indice de comorbilidad específico para trasplante alogénico de células progenitoras hematopoyéticas: cohorte retrospectiva de niños y adolescentes con enfermedad maligna / Specific comorbidity index for allogeneic hematopoietic stem cell transplantation: a retrospective cohort of children and adolescents with malignancies

Introducción: Entre las variables que afectan el riesgo de mortalidad relacionada (MRT) al trasplante alogénico de células progenitoras hematopoyéticas (TACPH) se incluyen las comorbilidades previas. Los índices de comorbilidad (IC) buscan mejorar la predicción de eventos combinando factores de riesgo independientes. Objetivos: 1) evaluar el uso de la versión breve y adaptada para niños, adolescentes y adultos jóvenes con enfermedad maligna del índice de comorbilidad específico para trasplante alogénico de células progenitoras hematopoyéticas (smyHCT-CI ); 2) evaluar el uso de los biomarcadores ferritina y albúmina en un índice de comorbilidad ampliado (smyHCT-CIa). Población y métodos: Diseño: cohorte retrospectiva. Periodo 2017- 2022. A cada p se le asignó nuevos puntajes utilizando el smyHCT-CI y el smyHCT-CIa. Los p se clasificaron en grupos de riesgo (GR) bajo (puntaje 0), intermedio (1-2) y alto (>3) con cada índice. Se comparó el n° de p asignado a cada GR grupo de riesgo y la MRT en cada grupo al usar el HCT-CI, el smyHCTCI y el smyHCT-CIa. Resultados: n 75. Frecuencia de p por GR según cada indicador (IC95): HCT-CI bajo 36 (25-47), intermedio 57 (56-69), alto 7 (1-12); smyHCT-CI: bajo 48 (37-59), intermedio 33 (23-44), alto 19 (10-27); smyHCT-CIa: bajo 43 (31-54), intermedio 36 (25-47), alto 21 (12-31). MRT por GR según indicador (IC95): HCT-CI: bajo 6,8 (14-28), intermedio 20,9 (9-33), alto 17,9 (0-55); smyHCT-CIa bajo 12,5 (1-24), intermedio 18,5 (4-33), alto 31,2 (9-54). Conclusión: El smyHCT-CI permitió identificar mejor los pacientes con mayor comorbilidad y riesgo de MRT. La ferritina resultó un biomarcador útil en la estimación del riesgo de MRT (AU)

Introduction: Variables affecting allogeneic hematopoietic stem cell transplantation (HCT) related mortality risk (TMR) include prior comorbidities. Comorbidity indices (CI) aim to improve event prediction by combining independent risk factors. Objectives: 1) to evaluate the use of the brief and adapted version of the HCT-specific comorbidity index for children, adolescents and young adults with malignancies (ymHCT-CI); 2) to evaluate the use of the biomarkers ferritin and albumin in an expanded comorbidity index (expanded ymHCT-CI). Population and methods: Design: retrospective cohort. Period 2017- 2022. Each patient was assigned new scores using the ymHCTCI and expanded ymHCT-CI. The p were classified into low (score 0), intermediate (1-2) and high (>3) risk groups (RG) with each index. The number of patients assigned to each RG and the TMR in each group were compared using the HCTCI, the ymHCT-CI, and the expanded ymHCT-CI. Results: n 75. Frequency of patients per RG according to each indicator (95%CI): HCT-CI low 36 (25-47), intermediate 57 (56-69), high 7 (1-12); ymHCT-CI: low 48 (37-59), intermediate 33 (23-44), high 19 (10-27); expanded ymHCT-CI: low 43 (31-54), intermediate 36 (25-47), high 21 (12-31). TMR by RG according to indicator (95%CI): HCT-CI: low 6.8 (14-28), intermediate 20.9 (9-33), high 17.9 (0-55); expanded ymHCT-CI low 12.5 (1-24), intermediate 18.5 (4-33), high 31.2 (9-54). Conclusion: ymHCT-CI allowed better identification of patients with higher comorbidity and risk of TMR. Ferritin proved to be a useful biomarker to estimate TMR risk (AU)

fMRI BOLD and MEG theta power reflect complementary aspects of activity during lexicosemantic decision in adolescents with ASD.

Neuroimaging studies of autism spectrum disorder (ASD) have been predominantly unimodal. While many fMRI studies have reported atypical activity patterns for diverse tasks, the MEG literature in ASD remains comparatively small. Our group recently reported atypically increased event-related theta power in individuals with ASD during lexicosemantic processing. The current multimodal study examined the relationship between fMRI BOLD signal and anatomically-constrained MEG (aMEG) theta power. Thirty-three adolescents with ASD and 23 typically developing (TD) peers took part in both fMRI and MEG scans, during which they distinguished between standard words (SW), animal words (AW), and pseudowords (PW). Regions-of-interest (ROIs) were derived based on task effects detected in BOLD signal and aMEG theta power. BOLD signal and theta power were extracted for each ROI and word condition. Compared to TD participants, increased theta power in the ASD group was found across several time windows and regions including left fusiform and inferior frontal, as well as right angular and anterior cingulate gyri, whereas BOLD signal was significantly increased in the ASD group only in right anterior cingulate gyrus. No significant correlations were observed between BOLD signal and theta power. Findings suggest that the common interpretation of increases in BOLD signal and theta power as 'activation' require careful differentiation, as these reflect largely distinct aspects of regional brain activity. Some group differences in dynamic neural processing detected with aMEG that are likely relevant for lexical processing may be obscured by the hemodynamic signal source and low temporal resolution of fMRI.

Reversal of age-associated frailty by controlled physical exercise: The pre-clinical and clinical evidences.

Demographic aging is one of the most serious challenges facing our society. Although we live longer, we do not live better because it is considered that approximately 16-20% of our life is spent in late-life morbidity. Older people have the greatest risk of developing frailty increasing the risk of presenting various adverse health events such as low quality of life, disability, hospitalization and even death. Frail men and women over 65 years old have lower muscle quality and muscle mass and higher percentage of body fat than non-frail people of the same age. In this review we will address the main physiological changes in the muscular and nervous system associated to aging. More specifically we will review the changes in muscle mass, quality, and strength relating them with the decrease in capillarization and muscular oxidative capacity as well as with the alterations in protein synthesis in the muscle with aging. The last section of the manuscript will be devoted to the animal models of frailty and the indexes developed to measure frailty in these models. We will finally address the importance of exercise training as an intervention to delay or even reverse frailty.

Decreased event-related theta power and phase-synchrony in young binge drinkers during target detection: An anatomically-constrained MEG approach.

BACKGROUND: The prevalence of binge drinking has risen in recent years. It is associated with a range of neurocognitive deficits among adolescents and young emerging adults who are especially vulnerable to alcohol use. Attention is an essential dimension of executive functioning and attentional disturbances may be associated with hazardous drinking. The aim of the study was to examine the oscillatory neural dynamics of attentional control during visual target detection in emerging young adults as a function of binge drinking. METHOD: In total, 51 first-year university students (18 ± 0.6 years) were assigned to light drinking ( n = 26), and binge drinking ( n = 25) groups based on their alcohol consumption patterns. A high-density magnetoencephalography signal was combined with structural magnetic resonance imaging in an anatomically constrained magnetoencephalography model to estimate event-related source power in a theta (4-7 Hz) frequency band. Phase-locked co-oscillations were further estimated between the principally activated regions during task performance. RESULTS: Overall, the greatest event-related theta power was elicited by targets in the right inferior frontal cortex and it correlated with performance accuracy and selective attention scores. Binge drinkers exhibited lower theta power and dysregulated oscillatory synchrony to targets in the right inferior frontal cortex, which correlated with higher levels of alcohol consumption. CONCLUSIONS: These results confirm that a highly interactive network in the right inferior frontal cortex subserves attentional control, revealing the importance of theta oscillations and neural synchrony for attentional capture and contextual maintenance. Attenuation of theta power and synchronous interactions in binge drinkers may indicate early stages of suboptimal integrative processing in young, highly functioning binge drinkers.

Functional and structural brain connectivity of young binge drinkers: a follow-up study.

Adolescence is a period of ongoing brain maturation characterized by hierarchical changes in the functional and structural networks. For this reason, the young brain is particularly vulnerable to the toxic effects of alcohol. Nowadays, binge drinking is a pattern of alcohol consumption increasingly prevalent among adolescents. The aim of the present study is to evaluate the evolution of the functional and anatomical connectivity of the Default Mode Network (DMN) in young binge drinkers along two years. Magnetoencephalography signal during eyes closed resting state as well as Diffusion Tensor Imaging (DTI) were acquired twice within a 2-year interval from 39 undergraduate students (22 controls, 17 binge drinkers) with neither personal nor family history of alcoholism. The group comparison showed that, after maintaining a binge drinking pattern along at least two years, binge drinkers displayed an increased brain connectivity of the DMN in comparison with the control group. On the other hand, the structural connectivity did not show significant differences neither between groups nor over the time. These findings point out that a continued pattern of binge drinking leads to functional alterations in the normal brain maturation process, even before anatomical changes can be detected.

Exploratory Analysis of Power Spectrum and Functional Connectivity During Resting State in Young Binge Drinkers: A MEG Study.

Binge Drinking (BD) is a pattern of intermittent intensive alcohol intake which has spread among young adults over the last decades. Adolescence constitutes a critical neuromaturation period in which the brain is particularly sensitive to the effects of alcohol. However, little is known about how BD affects the brain activity. This study aimed to characterize the brain's functional organization in BD and non-BD young population by means of analyzing functional connectivity (FC) and relative power spectra (PS) profiles measured with magnetoencephalography (MEG) during eyes-closed resting state. Our sample composed 73 first-year university students (35 BDs and 38 controls). Results showed that the BD subjects displayed a decreased alpha FC in frontal-parietal regions, and conversely, an enhanced FC in the delta, theta and beta bands in fronto-temporal networks. Besides the FC differences, the BD group showed a decreased PS within alpha range and an increased PS within theta range in the brain's occipital region. These differences in FC and PS measurements provide new evidence of the neurophysiological alterations related to the alcohol neurotoxicity and could represent an initial sign of an anomalous neural activity caused by a BD pattern of alcohol consumption during youth.

Drug polyconsumption is associated with increased synchronization of brain electrical-activity at rest and in a counting task.

Drug abusers typically consume not just one but several types of drugs, starting from alcohol and marijuana consumption, and then dramatically lapsing into addiction to harder drugs, such as cocaine, heroin, or amphetamine. The brain of drug abusers presents various structural and neurophysiological abnormalities, some of which may predate drug consumption onset. However, how these changes translate into modifications in functional brain connectivity is still poorly understood. To characterize functional connectivity patterns, we recorded Electroencephalogram (EEG) activity from 21 detoxified drug abusers and 20 age-matched control subjects performing a simple counting task and at rest activity. To evaluate the cortical brain connectivity network we applied the Synchronization Likelihood algorithm. The results showed that drug abusers had higher synchronization levels at low frequencies, mainly in the θ band (4-8 Hz) between frontal and posterior cortical regions. During the counting task, patients showed increased synchronization in the ß (14-35 Hz), and γ (35-45 Hz) frequency bands, in fronto-posterior and interhemispheric temporal regions. Taken together 'slow-down' at rest and task-related 'over-exertion' could indicate that the brain of drug abusers is suffering from a premature form of ageing. Future studies will clarify whether this condition can be reversed following prolonged periods of abstinence.