Association of serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-α) with diagnosis of delirium in oncology inpatients

Objective:To evaluate brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) blood levels as disease biomarkers of delirium in oncology inpatients.Methods:Seventeen oncology inpatients with delirium, 28 oncology inpatients without delirium, and 25 non-oncology controls (caregivers) were consecutively recruited from a Brazilian cancer center. This sample was matched by age, sex, and education level. The Confusion Assessment Method, the Mini-Mental State Examination, and the Digit Span Test were administered to ascertain delirium diagnosis. BDNF and TNF-α levels were measured by the Sandwich-ELISA method and flow cytometry, respectively. Blood samples were collected immediately after clinical evaluation.Results:Oncology inpatients (with and without delirium) showed significantly lower BDNF levels compared with non-oncology controls (F = 13.830; p = 0.001). TNF-α levels did not differ between the three groups.Conclusion:A cross-sectional relationship of BDNF and TNF-α blood levels with delirium in oncology inpatients was not demonstrated. The association between cancer and reduced serum BDNF levels may be mediated by confounding factors.

Atividade basal de acetilcolinesterase e níveis plasmáticos de serotonina não se associam ao delirium em pacientes gravemente enfermos / Baseline acetylcholinesterase activity and serotonin plasma levels are not associated with delirium in critically ill patients

RESUMO Objetivo: Investigar se os níveis plasmáticos de serotonina e atividade de acetilcolinesterase determinados por ocasião da admissão à unidade de terapia intensiva preveem a ocorrência de disfunção cerebral aguda em pacientes internados em unidade de terapia intensiva. Métodos: Foi conduzido no período entre maio de 2009 e setembro de 2010 um estudo prospectivo de coorte em uma amostra com 77 pacientes não consecutivos. A ocorrência de delirium foi determinada utilizando a ferramenta Confusion Assessment Method for the Intensive Care Unit, tendo sido determinadas as avaliações de acetilcolinesterase e serotonina em amostras de sangue coletadas até um máximo de 24 horas após admissão do paciente à unidade de terapia intensiva. Resultados: No presente estudo, 38 pacientes (49,6%) desenvolveram delirium durante sua permanência na unidade de terapia intensiva. Nem os níveis de atividade de acetilcolinesterase nem os de serotonina tiveram associação independente com delirium. Não se observaram correlações significantes entre atividade de acetilcolinesterase e níveis de serotonina com o número de dias livres de delirium/coma, porém, em pacientes que desenvolveram delirium, ocorreu uma forte correlação negativa entre níveis de acetilcolinesterase e número de dias livres de delirium/coma, demonstrando que níveis mais elevados de acetilcolinesterase se associaram com menos dias de vida sem delirium e coma. Nenhuma associação foi identificada entre os biomarcadores e mortalidade. Conclusão: Nem a atividade de acetilcolinesterase nem os níveis séricos de serotonina se associaram com delirium ou disfunção cerebral aguda em pacientes gravemente enfermos. A ocorrência de sepse não modificou esse relacionamento. .

ABSTRACT Objective: The aim of this study was to investigate whether plasma serotonin levels or acetylcholinesterase activities determined upon intensive care unit admission could predict the occurrence of acute brain dysfunction in intensive care unit patients. Methods: A prospective cohort study was conducted with a sample of 77 non-consecutive patients observed between May 2009 and September 2010. Delirium was determined using the Confusion Assessment Method for the Intensive Care Unit tool, and the acetylcholinesterase and serotonin measurements were determined from blood samples collected up to a maximum of 24 h after the admission of the patient to the intensive care unit. Results: In the present study, 38 (49.6%) patients developed delirium during their intensive care unit stays. Neither serum acetylcholinesterase activity nor serotonin level was independently associated with delirium. No significant correlations of acetylcholinesterase activity or serotonin level with delirium/coma-free days were observed, but in the patients who developed delirium, there was a strong negative correlation between the acetylcholinesterase level and the number of delirium/coma-free days, indicating that higher acetylcholinesterase levels are associated with fewer days alive without delirium or coma. No associations were found between the biomarkers and mortality. Conclusions: Neither serum acetylcholinesterase activity nor serotonin level was associated with delirium or acute brain dysfunction in critically ill patients. Sepsis did not modify these relationships. .

Riesgo de delirium durante la hospitalización en personas mayores: desarrollo y validación de un modelo de predicción clínica / Development and validation of a clinical predictive model for delirium in hospitalized older people

Background: Delirium is a prevalent problem among older patients and it is frequently underdiagnosed. Aim: To develop and validate a clinical predictive model to identify patients at high risk of delirium. Material and Methods: Two consecutive prospective cohort studies were used to develop and validate the model. The development cohort included 542 consecutive medical inpatients, 65 years or older. The validation cohort included 85 comparable patients. A predictive score was constructed with a multivariate analysis, using variables independently associated with delirium and subsequently tested in the new cohort. Patients were assessed within the first 48 hours of admission, and every 48 hours thereafter, using the Confusion Assessment Method to diagnose delirium, evaluating also the severity of underlying disease, comorbidities, functionality, and laboratory data. Results: Delirium occurred in 192 patients (35.4%) of the development cohort and was independently associated with age and functional status assessed using the Barthel Index. With these two variables, the predictive score for delirium was developed and tested rendering an area under the receiver operating characteristic (ROC) of 0.80 (confidence intervals 0.77-0.85). Cut-off points were chosen to establish low, intermediate, and high-risk groups for delirium. According to these cut-off points, delirium frequencies in the development cohort were 8%, 23%, and 69%, and in the validation cohort 5%, 34%, and 66%, respectively (c² p < 0.05). Conclusions: This simple predictive model based on age and functional status may be a useful tool for identifying older patients risking delirium.

Lack of association of S100 and neuron-specific enolase with mortality in critically ill patients

Objective: To evaluate the relationship between brain damage biomarkers and mortality in the intensive care unit (ICU). Methods: The sample comprised 70 patients admitted to an ICU. Blood samples were collected from all patients on ICU admission, and levels of S100β and neuron-specific enolase (NSE) were determined by ELISA. Results: Acute Physiologic and Chronic Health Evaluation (APACHE II) score was associated with mortality, but NSE and S100β were not associated with this outcome. In contrast, S100β levels were significantly higher in delirious and non-delirious patients who required mechanical ventilation during ICU stay. Conclusion: Levels of brain biomarkers at the time of ICU admission did not predict mortality in critically ill patients. .

Delirium in hospitalized elderly patients and post-discharge mortality

OBJECTIVE: To determine the impact of delirium on post-discharge mortality in hospitalized older patients. INTRODUCTION: Delirium is frequent in hospitalized older patients and correlates with high hospital mortality. There are only a few studies about its impact on post-discharge mortality. METHODS: This is a prospective study of patients over 60 years old who were hospitalized in the Geriatric Unit at Hospital das Clínicas of São Paulo between May 2006 and March 2007. Upon admission, demographics, comorbidities, number of drugs taken, and serum albumin concentration were evaluated for each patient. Delirium was diagnosed according to the DSM-IV criteria. Patients were divided into group A (with delirium) and group B (without delirium). One year after discharge, the patients or their caregivers were contacted to assess days of survival. RESULTS: The sample included 199 patients, 66 (33 percent) of whom developed delirium (Group A). After one year, 33 (50 percent) group A patients had died, and 45 (33.8 percent) group B patients had died (p = 0.03). There was a significant statistical difference in average age (p = 0.001) and immobility (p <0.001) between groups A and B. There were no statistically significant differences between groups A and B in number of drugs taken greater than four (p = 0.62), sex (p = 0.54) and number of diagnoses greater than four (p = 0.21). According to a multivariate analysis, delirium was not an independent predictor of post-discharge mortality. The predictors of post-discharge mortality were age > 80 years (p = 0.029), albumin concentration < 3.5 g/dl (p = 0.001) and immobility (p = 0.007). CONCLUSION: Delirium is associated with higher post-discharge mortality as a dependent predictor.