eoPred: predicting the placental phenotype of early-onset preeclampsia using public DNA methylation data.

Background: A growing body of literature has reported molecular and histological changes in the human placenta in association with preeclampsia (PE). Placental DNA methylation (DNAme) and transcriptomic patterns have revealed molecular subgroups of PE that are associated with placental histopathology and clinical phenotypes of the disease. However, the clinical and molecular heterogeneity of PE both across and within subtypes complicates the study of this disease. PE is most strongly associated with placental pathology and adverse fetal and maternal outcomes when it develops early in pregnancy. We focused on placentae from pregnancies affected by preeclampsia that were delivered before 34 weeks of gestation to develop eoPred, a predictor of the DNAme signature associated with the placental phenotype of early-onset preeclampsia (EOPE). Results: Public data from 83 placental samples (HM450K), consisting of 42 EOPE and 41 normotensive preterm birth (nPTB) cases, was used to develop eoPred-a supervised model that relies on a highly discriminative 45 CpG DNAme signature of EOPE in the placenta. The performance of eoPred was assessed using cross-validation (AUC = 0.95) and tested in an independent validation cohort (n = 49, AUC = 0.725). A subset of fetal growth restriction (FGR) and late-PE cases showed a similar DNAme profile at the 45 predictive CpGs, consistent with the overlap in placental pathology between these conditions. The relationship between the EOPE probability generated by eoPred and various phenotypic variables was also assessed, revealing that it is associated with gestational age, and it is not driven by cell composition differences. Conclusion: eoPred relies on a 45-CpG DNAme signature to predict a homogeneous placental phenotype of EOPE in a discrete or continuous manner. Using this classifier should 1) aid in the study of placental insufficiency and improve the consistency of future placental DNAme studies of PE, 2) facilitate identifying the placental phenotype of EOPE in public data sets and 3) importantly, standardize the placental diagnosis of EOPE to allow better cross-cohort comparisons. Lastly, classification of cases with eoPred will be useful for investigating the relationship between placental pathology and genetic or environmental variables.

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

INTRODUCCIÓN: Las microhemorragias cerebrales (MHC) son depósitos de hemosiderina, fagocitados por macrófagos, que se visualizan como imágenes hipointensas en determinadas secuencias de adquisición T2 de resonancia magnética cerebral. Existen muchas incógnitas acerca de su fisiopatología y significado clínico. DESARROLLO: Revisión bibliográfica de los principales estudios epidemiológicos, clínicos y anatomopatológicos de MHC en la población general, en pacientes con enfermedad o riesgo vascular y en pacientes con deterioro cognitivo. Descripción de la prevalencia, factores de riesgo, mecanismos fisiopatológicos y posibles implicaciones clínicas de las MHC. CONCLUSIONES: La prevalencia de las MHC es muy variable (3-27% en la población general, 6-80% en pacientes con enfermedad o riesgo vascular, 16-45% en pacientes con deterioro cognitivo). Las MHC se asocian a la edad, a la enfermedad de Alzheimer y, en particular, a la enfermedad vascular (hemorrágica o isquémica) cerebral. El sustrato patológico es la lipohialinosis (MHC subcorticales) o la angiopatía amiloide cerebral (MHC lobulares). Las MHC contribuyen al deterioro cognitivo, posiblemente a través de una desconexión córtico-subcortical e intracortical, y se asocian a una mayor mortalidad, especialmente de causa vascular. Las MHC aumentan el riesgo de sufrir hemorragia cerebral, especialmente en pacientes con múltiples MHC lobulares (probable angiopatía amiloide cerebral), por lo que el tratamiento anticoagulante podría estar contraindicado en estos pacientes. En pacientes con menor riesgo de sangrado, los nuevos anticoagulantes orales y la realización de un seguimiento combinado -clínico y mediante resonancia magnética- podrían ser útiles en la toma de decisiones

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

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.