Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition.

NAFLD is an important public health issue closely associated with the pervasive epidemics of diabetes and obesity. Yet, despite NAFLD being among the most common of chronic liver diseases, the biological factors responsible for its transition from benign nonalcoholic fatty liver (NAFL) to NASH remain unclear. This lack of knowledge leads to a decreased ability to find relevant animal models, predict disease progression, or develop clinical treatments. In the current study, we used multiple mouse models of NAFLD, human correlation data, and selective gene overexpression of steroidogenic acute regulatory protein (StarD1) in mice to elucidate a plausible mechanistic pathway for promoting the transition from NAFL to NASH. We show that oxysterol 7α-hydroxylase (CYP7B1) controls the levels of intracellular regulatory oxysterols generated by the "acidic/alternative" pathway of cholesterol metabolism. Specifically, we report data showing that an inability to upregulate CYP7B1, in the setting of insulin resistance, results in the accumulation of toxic intracellular cholesterol metabolites that promote inflammation and hepatocyte injury. This metabolic pathway, initiated and exacerbated by insulin resistance, offers insight into approaches for the treatment of NAFLD.

StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis.

How plasma membrane (PM) cholesterol is controlled is poorly understood. Ablation of the gene encoding the ER stress steroidogenic acute regulatory-related lipid transfer domain (StarD)5 leads to a decrease in PM cholesterol content, a decrease in cholesterol efflux, and an increase in intracellular neutral lipid accumulation in macrophages, the major cell type that expresses StarD5. ER stress increases StarD5 expression in mouse hepatocytes, which results in an increase in accessible PM cholesterol in WT but not in StarD5-/- hepatocytes. StarD5-/- mice store higher levels of cholesterol and triglycerides, which leads to altered expression of cholesterol-regulated genes. In vitro, a recombinant GST-StarD5 protein transfers cholesterol between synthetic liposomes. StarD5 overexpression leads to a marked increase in PM cholesterol. Phasor analysis of 6-dodecanoyl-2-dimethylaminonaphthalene fluorescence lifetime imaging microscopy data revealed an increase in PM fluidity in StarD5-/- macrophages. Taken together, these studies show that StarD5 is a stress-responsive protein that regulates PM cholesterol and intracellular cholesterol homeostasis.

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

ER stress increases StarD5 expression by stabilizing its mRNA and leads to relocalization of its protein from the nucleus to the membranes.

StarD5 belongs to the StarD4 subfamily of steroidogenic acute regulatory lipid transfer (START) domain proteins. In macrophages, StarD5 is found in the cytosol and maintains a loose association with the Golgi. Like StarD1 and StarD4, StarD5 is known to bind cholesterol. However, its function and regulation remain poorly defined. Recently, it has been shown that its mRNA expression is induced in response to different inducers of endoplasmic reticulum (ER) stress. However, the molecular mechanism(s) involved in the induction of StarD5 expression during ER stress is not known. Here we show that in 3T3-L1 cells, the ER stressor thapsigargin increases intracellular free cholesterol due to an increase in HMG-CoA reductase expression. Activation of StarD5 expression is mediated by the transcriptional ER stress factor XBP-1. Additionally, the induction of ER stress stabilizes the StarD5 mRNA. Furthermore, StarD5 protein is mainly localized in the nucleus, and upon ER stress, it redistributes away from the nucleus, localizing prominently to the cytosol and membranes. These results reveal the increase in StarD5 expression and protein redistribution during the cell protective phase of the ER stress, suggesting a role for StarD5 in cholesterol metabolism during the ER stress response.

Subcellular localization and regulation of StarD4 protein in macrophages and fibroblasts.

StarD4 is a member of the StarD4 subfamily of START domain proteins with a characteristic lipid binding pocket specific for cholesterol. The objective of this study was to define StarD4 subcellular localization, regulation, and function. Immunobloting showed that StarD4 is highly expressed in the mouse fibroblast cell line 3T3-L1, in human THP-1 macrophages, Kupffer cells (liver macrophages), and hepatocytes. In 3T3-L1 cells and THP-1 macrophages, StarD4 protein appeared localized to the cytoplasm and the endoplasmic reticulum (ER). More specifically, in THP-1 macrophages StarD4 co-localized to areas of the ER enriched in Acyl-CoA:cholesterol acyltransferase-1 (ACAT-1), and was closely associated with budding lipid droplets. The addition of purified StarD4 recombinant protein to an in vitro assay increased ACAT activity 2-fold, indicating that StarD4 serves as a rate-limiting step in cholesteryl ester formation by delivering cholesterol to ACAT-1-enriched ER. In addition, StarD4 protein was found to be highly regulated and to redistribute in response to sterol levels. In summary, these observations, together with our previous findings demonstrating the ability of increased StarD4 expression to increase bile acid synthesis and cholesteryl ester formation, provide strong evidence for StarD4 as a highly regulated, non-vesicular, directional, intracellular transporter of cholesterol which plays a key role in the maintenance of intracellular cholesterol homeostasis.

alpha(1)-fetoprotein transcription factor (FTF)/liver receptor homolog-1 (LRH-1) is an essential lipogenic regulator.

alpha(1)-Fetoprotein transcription factor (FTF), also known as liver receptor homolog 1 (LRH-1) is highly expressed in the liver and intestine, where it is implicated in the regulation of cholesterol, bile acid and steroid hormone homeostasis. FTF is an important regulator of bile acid metabolism. We show here that FTF plays a key regulatory role in lipid homeostasis including triglyceride and cholesterol homeostasis. FTF deficient mice developed lower levels of serum triglyceride and cholesterol as a result of lower expression of several hepatic FTF target genes. Chenodeoxycholic acid repressed FTF expression resulting in a decrease in serum triglyceride in wild-type mice. The absence of chenodeoxycholic acid-mediated repression in FTF(+/-) mice demonstrated the essential role of FTF in triglyceride metabolism. Taken together, our results identify the nuclear receptor FTF as a central regulator of lipid metabolism.

α(1)-Fetoprotein Transcription Factor (FTF)/Liver Receptor Homolog-1 (LRH-1) Is an Essential Lipogenic Regulator.

α(1)-Fetoprotein transcription factor (FTF), also known as liver receptor homolog 1 (LRH-1) is highly expressed in liver and intestine, where it is implicated in the regulation of cholesterol, bile acid and steroid hormone homeostasis. FTF is an important regulator of bile acid metabolism. We show here that FTF plays a key regulatory role in lipid homeostasis including triglyceride and cholesterol homeostasis. FTF deficient mice developed lower levels of serum triglyceride and cholesterol as a result of lower expression of several hepatic FTF target genes. Chenodeoxycholic acid repressed FTF expression resulting in a decrease in serum triglyceride in wild-type mice. The absence of chenodeoxycholic acid-mediated repression in FTF(+/-) mice demonstrated the essential role of FTF in triglyceride metabolism. Taken together, our results identify the nuclear receptor FTF as a central regulator of lipid metabolism.

Functional, Clinical, and Sociodemographic Variables Associated with Risk of In-Hospital Mortality by COVID-19 in People over 80 Years Old.

OBJECTIVES: The objective is to assess the role of functional, clinical, and analytic parameters in predicting mortality in older patients hospitalized due to COVID-19. DESIGN: Cohort study with a mean follow-up of 12.8 days. SETTING: Public university hospital (Madrid, Spain). PARTICIPANTS: 499 patients 80 and above consecutively admitted to a Spanish public university hospital between 4 March 2020 and 16 May 2020. MEASUREMENTS: Mortality was the main outcome. Data of sociodemographic variables (age, sex, living), comorbidities, polypharmacy, functional status, date of hospital admission and length of stay was recorded. Clinical symptoms, laboratory and X-ray findings were collected at time of admission. For multivariant analysis, logistic regressions were performed to identify risk factors for death. RESULTS: Mean age was 86.7±4.4 with 37% of death. Mortality was associated with male gender [odds ratio (OR) 1.50; 95% confidence interval (CI) 1.01-2.24], with a 5-points increase on Barthel Index [OR 1.01 (95%CI 1.00-1.02)], higher Charlson Index score [OR 1.13 (95%CI 1.02-1.26)] and comorbidities [OR 1.28 (95%CI 1.06-1.53)], hyperpolipharmacy [OR 2.00 (95%CI 1.04-3.82)], unilateral pneumonia [OR 1.83 (95%CI 1.01-3.30)], higher levels of C-reactive protein [OR 1.09 (95%CI 1.06-1.12)] and creatine [OR 1.48 (95%CI 1.15-1.89)]. Higher oxygen levels were a protective factor [OR 0.92 (95%CI 0.89-0.95)]. CONCLUSIONS: Functional status, being male, a higher burden of comorbidities, hyperpolipharmacy, unilateral pneumonia and some laboratory parameters predict in-hospital mortality in this older population. The knowledge of these mortality risk factors should be used to improve the survival of older hospitalized patients.

Bile acids regulate hepatic gluconeogenic genes and farnesoid X receptor via G(alpha)i-protein-coupled receptors and the AKT pathway.

Bile acids are important regulatory molecules that can activate specific nuclear receptors and cell signaling pathways in the liver and gastrointestinal tract. In the current study, the chronic bile fistula (CBF) rat model and primary rat hepatocytes (PRH) were used to study the regulation of gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) and the gene encoding short heterodimeric partner (SHP) by taurocholate (TCA). The intestinal infusion of TCA into the CBF rat rapidly (1h) activated the AKT (approximately 9-fold) and ERK1/2 (3- to 5-fold) signaling pathways, downregulated (approximately 50%, 30 min) the mRNA levels of PEPCK and G-6-Pase, and induced (14-fold in 3 h) SHP mRNA. TCA rapidly ( approximately 50%, 1-2 h) downregulated PEPCK and G-6-Pase mRNA levels in PRH. The downregulation of these genes by TCA was blocked by pretreatment of PRH with pertussis toxin (PTX). In PRH, TCA plus insulin showed a significantly stronger inhibition of glucose secretion/synthesis from lactate and pyruvate than either alone. The induction of SHP mRNA in PRH was strongly blocked by inhibition of PI3 kinase or PKCzeta by specific chemical inhibitors or knockdown of PKCzeta by siRNA encoded by a recombinant lentivirus. Activation of the insulin signaling pathway appears to be linked to the upregulation of farnesoid X receptor functional activity and SHP induction.

Structural and functional patterns in healthy aging, mild cognitive impairment, and Alzheimer disease.

The aim of this study was to analyze the combined contribution of magnetic resonance imaging and magnetoencephalography (MEG) to the diagnosis of mild cognitive impairment (MCI) and AD. To whole-head MEG recordings were obtained from three diagnosis groups: Alzheimer disease (AD), MCI, and control. Magnetic resonance imaging volumetric data of global brain, temporal lobe, and hippocampal volumes, were also obtained. Results indicated that a reduction of volume in the hippocampal structure allowed the discrimination between AD and MCI patients as compared with controls. The percentage of correct classification was 91.3% when AD versus controls was compared, and 83.3% when we compared MCI versus control. MEG data showed that AD patients exhibit higher theta and delta activity than MCI and controls. Such higher activity was significant in parietal, temporal, and occipital areas. Left parietal theta classified controls versus MCIs with 78.3% rate of correct classification. Right occipital theta and the left parietal delta allowed the discrimination of controls versus ADs, with 81.8% rate of correct classification. Left parietal theta discriminated between ADs and MCIs with 56.6% rate of correct classification. In addition, the combination of both techniques significantly improved the rate of correct classification, thus indicating that a multidisciplinary perspective of techniques may improve the diagnostic capabilities.

Complexity analysis of spontaneous brain activity in Alzheimer disease and mild cognitive impairment: an MEG study.

Nonlinear analyses have shown that Alzheimer disease (AD) patients' brain activity is characterized by a reduced complexity and connectivity. The aim of this study is to define complexity patterns of mild cognitive impairment (MCI) patients. Whole-head magnetoencephalography recordings were obtained from 18 diagnosed AD patients, 18 MCI patients, and 18 healthy controls during resting conditions. Lempel-Ziv complexity (LZC) values were calculated. MCI patients exhibited intermediary LZC scores between AD patients and controls. A combination of age and posterior LZC scores allowed ADs-MCIs discrimination with 94.4% sensitivity and specificity, whereas no LZC score allowed MCIs---controls discrimination. AD patients and controls showed a parallel tendency to diminished LZC scores as a function of age, but MCI patients did not exhibit such "normal" tendency. Accordingly, anterior LZC scores allowed MCIs-controls discrimination for subjects below 75 years. MCIs exhibited a qualitatively distinct relationship between aging and complexity reduction, with scores higher than controls in older individuals. This fact might be considered a new example of compensatory mechanism in MCI before fully established dementia.

[Prognostic value of functional assessment at admission in an emergency short-stay unit]. / Valor pronóstico de la valoración funcional al ingreso en una unidad de corta estancia de Urgencias.

INTRODUCTION: To determine the prognostic value of functional impairment on the final destination of elders admitted for acute medical illness to an emergency short-stay unit (ESSU). MATERIAL AND METHODS: We performed a prospective analysis of patients aged more than 65 years old admitted to the ESSU of Hospital Clínico San Carlos in Madrid in April 2008. A protocol was designed that included epidemiologic variables (age and gender), clinical variables (reason for admission, comorbidity measured by the Charlson Index [CI]) and functional variables (previous, admission and functional decline [FD] measured with the Barthel [BI] and Lawton Indexes [LI]). The prognostic value of FD on the decision to admit patients was analyzed through ROC curves and the cut points that maximized sensitivity and specificity were determined. RESULTS: Sixty patients were included with a mean age of 80.7 (SD 8.2) years and 71.7% were women. The reasons for admission were acute infections in 31.7%, heart failure in 23.3%, syncope in 15.0%, intestinal obstruction in 11.7%, gastrointestinal bleeding in 10.0%, and arrhythmias in 8.3%. The mean CI was 2.27 (1.45). Functional assessment was as follows: mean previous BI score: 79.25 (SD 25) and at admission: 62.92 (SD 28.19). Mean previous LI score: 4.85 (SD 2.45) and at admission: 2.98 (SD 2.42).): BI-FD: 20% (1.25-38.23), LI-FD 37.5% (16.7-70.2%). FD was found in 100% of the patients. The mean length of stay was 1.70 (SD 0.62) days. Discharge destination was home discharge in 46.7% and hospitalization unit in 53.3%. Multivariate analysis according to discharge destination (home vs hospitalization) provided the following results : BI-FI > or = 16% (OR=7.99 [1.1-60.5], p=0.037), LI-FI > or =35% (OR=19.6 [0.04-0.52], p <0.0001). CONCLUSIONS: Patients with significant FD in the emergency room should not be admitted to an ESSU since significant FD is a prognostic factor for transfer to a conventional ward.

Bile acids as regulatory molecules.

In the past, bile acids were considered to be just detergent molecules derived from cholesterol in the liver. They were known to be important for the solubilization of cholesterol in the gallbladder and for stimulating the absorption of cholesterol, fat-soluble vitamins, and lipids from the intestines. However, during the last two decades, it has been discovered that bile acids are regulatory molecules. Bile acids have been discovered to activate specific nuclear receptors (farnesoid X receptor, preganane X receptor, and vitamin D receptor), G protein coupled receptor TGR5 (TGR5), and cell signaling pathways (c-jun N-terminal kinase 1/2, AKT, and ERK 1/2) in cells in the liver and gastrointestinal tract. Activation of nuclear receptors and cell signaling pathways alter the expression of numerous genes encoding enzyme/proteins involved in the regulation of bile acid, glucose, fatty acid, lipoprotein synthesis, metabolism, transport, and energy metabolism. They also play a role in the regulation of serum triglyceride levels in humans and rodents. Bile acids appear to function as nutrient signaling molecules primarily during the feed/fast cycle as there is a flux of these molecules returning from the intestines to the liver following a meal. In this review, we will summarize the current knowledge of how bile acids regulate hepatic lipid and glucose metabolism through the activation of specific nuclear receptors and cell signaling pathways.

Mitochondrial oxysterol biosynthetic pathway gives evidence for CYP7B1 as controller of regulatory oxysterols.

The aim of this paper was to more completely study the mitochondrial CYP27A1 initiated acidic pathway of cholesterol metabolism. The mitochondrial CYP27A1 initiated pathway of cholesterol metabolism (acidic pathway) is known to synthesize two well-described vital regulators of cholesterol/lipid homeostasis, (25R)-26-hydroxycholesterol (26HC) and 25-hydroxycholesterol (25HC). Both 26HC and 25HC have been shown to be subsequently 7α-hydroxylated by Cyp7b1; reducing their regulatory abilities and furthering their metabolism to chenodeoxycholic acid (CDCA). Cholesterol delivery into the inner mitochondria membrane, where CYP27A1 is located, is considered the pathway's only rate-limiting step. To further explore the pathway, we increased cholesterol transport into mitochondrial CYP27A1 by selectively increased expression of the gene encoding the steroidogenic acute transport protein (StarD1). StarD1 overexpression led to an unanticipated marked down-regulation of oxysterol 7α-hydroxylase (Cyp7b1), a marked increase in 26HC, and the formation of a third vital regulatory oxysterol, 24(S)-hydroxycholesterol (24HC), in B6/129 mice livers. To explore the further metabolism of 24HC, as well as, 25HC and 26HC, characterizations of oxysterols and bile acids using three murine models (StarD1 overexpression, Cyp7b1-/-, Cyp27a1-/-) and human Hep G2 cells were conducted. This report describes the discovery of a new mitochondrial-initiated pathway of oxysterol/bile acid biosynthesis. Just as importantly, it provides evidence for CYP7B1 as a key regulator of three vital intracellular regulatory oxysterol levels.

Increased biomagnetic activity in the ventral pathway in mild cognitive impairment.

OBJECTIVE: Mild cognitive impairment (MCI) patients represent an intermediary state between healthy aging and dementia. MCI activation profiles, recorded during a memory task, have been studied either through high spatial resolution or high temporal resolution techniques. However, little is known about the benefit of combining both dimensions. Here, we investigate, by means of magnetoencephalography (MEG), whether spatio-temporal profiles of neuromagnetic activity could differentiate between MCI and age-matched elderly participants. METHODS: Taking the advantage of the high temporal resolution and good spatial resolution of MEG, neuromagnetic activity from 15 elderly MCI patients and 20 age-matched controls was recorded during the performance of a modified version of the Sternberg paradigm. RESULTS: Behavioral performance was similar in both groups. A between group analysis revealed that MCI patients showed bilateral higher activity in the ventral pathway, in both the target and the non-target stimuli. A within-group analysis of the target stimuli, indicates a lack of asymmetry through all late latency windows in both groups. CONCLUSIONS: MCI patients showed a compensatory mechanism represented by an increased bilateral activity of the ventral pathway in order to achieve a behavioral performance similar to the control group. SIGNIFICANCE: This spatio-temporal pattern of activity could be another tool to differentiate between healthy aging and MCI patients.

Brain microbleeds: Epidemiology and clinical implications. / Microhemorragias cerebrales: epidemiología e implicaciones clínicas.

INTRODUCTION: Brain microbleeds (BMB) are haemosiderin deposits contained within macrophages, which are displayed as hypointense images in some T2-weighted magnetic resonance imaging sequences. There are still many questions to be answered about the pathophysiology and clinical relevance of BMB. DEVELOPMENT: We conducted a literature review of the main epidemiological, clinical, and anatomical pathology studies of BMB performed in the general population, in patients at risk of or already suffering from a vascular disease, and in patients with cognitive impairment. We analysed the prevalence of BMB, risk factors, and potential pathophysiological mechanisms and clinical implications. CONCLUSIONS: The prevalence of BMB is highly variable (3%-27% in the general population, 6%-80% in patients with vascular risk factors or vascular disease, and 16%-45% in patients with cognitive impairment). BMB are associated with ageing, Alzheimer disease (AD), and in particular haemorrhagic or ischaemic cerebrovascular disease. The pathological substrate of BMB is either lipohyalinosis (subcortical BMB) or cerebral amyloid angiopathy (lobar BMB). BMB exacerbate cognitive impairment, possibly through cortical-subcortical and intracortical disconnection, and increase the risk of death, mostly due to vascular causes. BMB also increase the risk of cerebral haemorrhage, particularly in patients with multiple lobar BMB (probable erebral amyloid angiopathy). Therefore, anticoagulant treatment may be contraindicated in these patients. In patients with lower risk of bleeding, the new oral anticoagulants and the combination of clinical and magnetic resonance imaging follow-up could be helpful in the decision-making process.

In-hospital mortality risk score for very old patients hospitalized with decompensated chronic heart failure.

OBJECTIVE: To derive a risk score to predict in-hospital mortality for very old patients with decompensated chronic heart failure (DCHF). METHODOLOGY: Retrospective cohort study that included patients ≥ 80 years admitted to a Geriatric Acute Care Unit with DCHF between January 2012 and December 2014. We analyzed 70 candidate risk factors and in-hospital mortality. We derived a risk model using multivariate logistic regression model and constructed a scale for scoring risk. We used bootstrapping techniques for the internal validation. RESULTS: We included 629 patients with mean age of 90 (SD5) years, 470 (73.1%) being women. Eighty-six (13.7%) patients died during the hospitalization. Factors included in the final risk model were NYHA class III-IV, severe functional dependence (Katz activities of daily living index < 2), infection as cause of exacerbation of heart failure, number of medications ≥ 8, albumin < 3 mg/dL, glomerular filtration rate < 60 mL/min, level of potassium in blood > 5.5 mEq/L and red blood cell distribution width (RDW) > 17%. In-hospital mortality in risk groups was 3.0, 4.6, 9.5, 15.1 and 36.3%, respectively. The area under ROC curve risk for score after bootstrapping was 0.77 (95%: CI 0.70-0.83). CONCLUSION: This risk score could be useful for stratifying risk for in-hospital mortality among very old patients admitted to hospital for DCHF.

Multidimensional intervention to improve the short-term prognosis of frail elderly patients discharged from a short-stay unit: A quasiexperimental study. / Intervención multidimensional que mejora el pronóstico a corto plazo entre los ancianos frágiles dados de alta desde una unidad de corta estancia: estudio cuasiexperimental.

OBJECTIVE: To study the effect of a multidimensional intervention on the prognosis at 30 days for frail elderly patients discharged from a short-stay unit. MATERIAL AND METHOD: A quasiexperimental study was conducted with a historical control cohort. We included frail patients (Identification of Seniors at Risk score≥2) 75 years of age or older, discharged from an short-stay unit over 2 months in 2013 (control group) and in 2016 (intervention group). An intervention was conducted based on the activation of resources, based on the deficiencies detected after an abbreviated geriatric assessment, in conjunction with Primary Care. The main endpoint was the presence of an adverse result (death or readmission for any cause or severe functional impairment) at 30 days of discharge. RESULTS: We included 137 (62.8%) patients in the intervention group and 81 (37.2%) in the control group. Eighteen (13.1%) patients in the intervention group and 29 (35.8%) in the control group presented an adverse event at 30 days. A multivariate analysis showed that the implementation of a multidimensional intervention was a protective factor for presenting an adverse event at 30 days of discharge (adjusted RR 0.40; 95% CI 0.23-0.68; P=.001). CONCLUSIONS: The implementation of an individual care plan for frail elderly patients, based on the activation of resources according to the deficiencies detected after an abbreviated geriatric assessment and in conjunction with Primary Care, could improve the results at 30 days of discharge from an short-stay unit.

[Oral anticoagulation therapy in the elderly population with atrial fibrillation. A review article]. / Anticoagulación en población anciana con fibrilación auricular no valvular. Artículo de revisión.

Aging is an important risk factor for patients with atrial fibrillation. The estimated prevalence of atrial fibrillation in patients aged ≥80 years is 9-10%, and is associated with a four to five fold increased risk of embolic stroke, and with an estimated increased stroke risk of 1.45-fold per decade in aging. Older age is also associated with an increased risk of major bleeding with oral anticoagulant therapy. This review will focus on the role of oral anticoagulation with new oral anticoagulants, non-vitamin K antagonist in populations with common comorbid conditions, including age, chronic kidney disease, coronary artery disease, on multiple medication, and frailty. In patients 75 years and older, randomised trials have shown new oral anticoagulants to be as effective as warfarin, or in some cases superior, with an overall better safety profile, consistently reducing rates of intracranial haemorrhages. Prior to considering oral anticoagulant therapy in an elderly frail patient, a comprehensive assessment should be performed to include the risks and benefits, stroke risk, baseline kidney function, cognitive status, mobility and fall risk, multiple medication, nutritional status assessment, and life expectancy.

[Clinical assessment and diagnostic tools]. / Evaluación clínica y herramientas diagnósticas.

The presence of cognitive impairment generates important changes in both affected individuals and their families and the health staff who must provide adequate care. Early identification of this alteration allows appropriate diagnosis and treatment and psychosocial and educational support, as well as the possibility of establishing care, life and financial plans. The interest of the scientific community in age-related cognitive alterations is demonstrated by the abundance of criteria and classifications. Obviously, there is a need to unify these criteria and implement longitudinal studies in order to reach reliable conclusions. Clinical assessment of the distinct cognitive domains should include careful history-taking and the use of diagnostic neuropsychological batteries. First, the ideal screening test would be one that could be administered in a few minutes, with a cut-off point that would identify patients requiring further assessment for correct diagnosis. The use of dynamic biomarkers is based on the hypothesis that they have a specific time-dependent model. These biomarkers include, firstly, markers of amyloidosis and, secondly, markers of neurodegeneration. Cognitive frailty is an emerging term inspired by a potential parallel with physical frailty syndrome. A subgroup of patients with cognitive impairment show a reduced capacity for recovery and functional decline that interact with physical frailty. The evidence suggests that cognitive status represents an important dimension of frailty syndrome.