Prognostic value of cerebrospinal fluid biomarkers in mild cognitive impairment due to Alzheimer disease

We performed a retrospective analysis of the patients assessed at our memory unit for whom Alzheimer disease (AD) cerebrospinal fluid biomarker results were available. We selected patients diagnosed with mild cognitive impairment due to AD (National Institute on Aging-Alzheimer’s Association clinical criteria), confirmed neuropsychological deficit, a Global Deterioration Scale score of 3, and an abnormal profile of cerebrospinal fluid biomarkers. Of the 588 cases reviewed, 110 met the inclusion criteria. During follow-up, 50 cases (45.45%) progressed to dementia due to AD. Baseline levels of total and phosphorylated tau were higher in the group of patients that progressed to dementia than in those remaining with mild cognitive impairment. After adjusting for age, sex, history of hypertension, diabetes, and educational level, a 10% increase in total tau protein values was associated with a 7.60% increase in the risk of progression to dementia (hazard ratio: 2.22; 95% confidence interval, 1.28–3.84]; P = .004). Among patients with mild cognitive impairment due to AD and abnormal cerebrospinal fluid biomarker profiles, progressively higher concentrations of total or phosphorylated tau were associated with increased risk of progression to dementia. Resumen: Realizamos un análisis retrospectivo de los pacientes evaluados en nuestra unidad de memoria en los que se realizó determinación de biomarcadores licuorales de enfermedad de Alzheimer (EA). Se seleccionaron aquellos casos con diagnóstico de deterioro cognitivo leve debido a EA según criterios clínicos (criterios NIA-AA), déficit neuropsicológico comprobado, una puntuación igual a 3 en la escala GDS y un perfil alterado de biomarcadores en líquido cefalorraquídeo. De los 588 casos revisados, 110 cumplieron los criterios de inclusión. Durante el seguimiento, 50 de estos 110 casos (45,45%) progresaron a demencia por EA. Se observaron diferencias significativas en los niveles basales de tau total y tau fosforilada entre los casos que evolucionaron a demencia y los que permanecieron estables como deterioro cognitivo leve, siendo los niveles más altos en el grupo que progresó a demencia. Después del ajuste por edad, sexo, antecedentes de hipertensión, diabetes y nivel educativo, un aumento del 10% en los valores de proteína tau total se asoció con un aumento del 7,60% en el riesgo de progresión a demencia (HR = 2,22, IC 95% [1,28, 3.84], P = .004). En pacientes con deterioro cognitivo leve debido a EA un perfil alterado de biomarcadores licuorales, concentraciones progresivamente mayores de tau-t y tau-p se asocian a un mayor riesgo de conversión a demencia

Development and validation of a score to predict postoperative respiratory failure in a multicentre European cohort : A prospective, observational study

BACKGROUND Postoperative respiratory failure (PRF) is the most frequent respiratory complication following surgery. OBJECTIVE The objective of this study was to build a clinically useful predictive model for the development of PRF. DESIGN A prospective observational study of a multicentre cohort. SETTING Sixty-three hospitals across Europe. PATIENTS Patients undergoing any surgical procedure under general or regional anaesthesia during 7-day recruitment periods. MAIN OUTCOME MEASURES Development of PRF within 5 days of surgery. PRF was defined by a partial pressure of oxygen in arterial blood (PaO2) less than 8 kPa or new onset oxyhaemoglobin saturation measured by pulse oximetry (SpO(2)) less than 90% whilst breathing room air that required conventional oxygen therapy, noninvasive or invasive mechanical ventilation. RESULTS PRF developed in 224 patients (4.2% of the 5384 patients studied). In-hospital mortality [95% confidence interval (95% CI)] was higher in patients who developed PRF [10.3% (6.3 to 14.3) vs. 0.4% (0.2 to 0.6)]. Regression modelling identified a predictive PRF score that includes seven independent risk factors: low preoperative SpO(2); at least one preoperative respiratory symptom; preoperative chronic liver disease; history of congestive heart failure; open intrathoracic or upper abdominal surgery; surgical procedure lasting at least 2 h; and emergency surgery. The area under the receiver operating characteristic curve (c-statistic) was 0.82 (95% CI 0.79 to 0.85) and the Hosmer-Lemeshow goodness-of-fit statistic was 7.08 (P = 0.253). CONCLUSION A risk score based on seven objective, easily assessed factors was able to predict which patients would develop PRF. The score could potentially facilitate preoperative risk assessment and management and provide a basis for testing interventions to improve outcomes. The study was registered at ClinicalTrials.gov (identifier NCT01346709)