RESUMO
Human brain possesses a unique anatomy and physiology. For centuries, methodological barriers and ethical challenges in accessing human brain tissues have restricted researchers into using 2-D cell culture systems and model organisms as a tool for investigating the mechanisms underlying neurological disorders in humans. However, our understanding regarding the human brain development and diseases has been recently extended due to the generation of 3D brain organoids, grown from human stem cells or induced pluripotent stem cells (iPSCs). This system evolved into an attractive model of brain diseases as it recapitulates to a great extend the cellular organization and the microenvironment of a human brain. This chapter focuses on the application of brain organoids in modelling several neurodevelopmental and neurodegenerative diseases.
Assuntos
Encéfalo/patologia , Doenças Neurodegenerativas/patologia , Transtornos do Neurodesenvolvimento/patologia , Organoides/patologia , Humanos , Células-Tronco Pluripotentes Induzidas/patologiaRESUMO
Cardiogenic shock (CS) presents with a complex spectrum of low output states, which can be provoked by Acute Coronary Syndrome (ACS) or Acute Decompensated Heart Failure (ADHF). Its management includes hemodynamic assessment via right heart catheterization (RHC). Herein, we describe the timing of RHC based on the etiology and severity of CS as defined by the Society of Cardiovascular Angiography & Interventions (SCAI) Shock Classification. We performed a single-center retrospective analysis of patients admitted with CS secondary to ACS or ADHF from January 7, 2018 to June 30, 2020 at the University of Iowa Hospitals and Clinics. Among the 647 patients admitted, 249 patients had RHC during their admission. Of those, 51 had underlying ACS and 198 had ADHF. The overall time from admission to invasive hemodynamic assessment was 2.73 days. The mean time for SCAI-A was 3.6 ± 2.8 days, SCAI-B 3.7 ± 3.7 days, SCAI-C 2.6 ± 3.0 days, SCAI-D 2.5 ± 4.1 days, and SCAI-E 1.3 ± 2.1 days. The linear regression model showed that RHC was performed earlier in patients with worse hemodynamics evaluated by Cardiac Power Output (CPO) (Coefficient 0.14, R- squared 0.01, Pâ¯=â¯0.03). Hemodynamic parameters showed that high PAPi, RVSWi, and Cardiac Power Output during admission predicted low in-hospital mortality (P < 0.01). RHC was performed earlier in more critically ill patients. Patients with CS in the setting of ACS underwent RHC significantly earlier than those with ADHF.
Assuntos
Síndrome Coronariana Aguda , Insuficiência Cardíaca , Humanos , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Estudos Retrospectivos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/complicações , Hospitalização , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/terapia , Cateterismo Cardíaco/efeitos adversosRESUMO
BACKGROUND: Immunoglobulin A nephropathy (IgAN) is among the commonest glomerulonephritides in Greece and an important cause of end-stage kidney disease (ESKD) with an insidious chronic course. Thus, the recently published International IgAN prediction tool could potentially provide valuable risk stratification and guide the appropriate treatment module. This study aimed to externally validate this prediction tool using a patient cohort from the IgAN registry of the Greek Society of Nephrology. METHODS: We validated the predictive performance of the two full models (with or without race) derived from the International IgAN Prediction Tool study in the Greek Society of Nephrology registry of patients with IgAN using external validation of survival prediction models (Royston and Altman). The discrimination and calibration of the models were tested using the C-statistics and stratified analysis, coefficient of determination ( R D 2 ) for model fit, and the regression coefficient of the linear predictor (ßPI), respectively. RESULTS: The study included 264 patients with a median age of 39 (30-51) years where 65.2% are men. All patients were of Caucasian origin. The 5-year risk of the primary outcome (50% reduction in estimated glomerular filtration rate or ESKD) was 8%. The R D 2 for the full models with and without race when applied to our cohort was 39 and 35%, respectively, and both were higher than the reported R D 2 for the models applied to the original validation cohorts (26.3, 25.3, and 35.3%, respectively). Harrel's C statistic for the full model with race was 0.71, and for the model without race was 0.70. Renal survival curves in the subgroups (<16th, ~16 to <50th, ~50 to <84th, and >84th percentiles of linear predictor) showed adequate separation. However, the calibration proved not to be acceptable for both the models, and the risk probability was overestimated by the model. CONCLUSIONS: The two full models with or without race were shown to accurately distinguish the highest and higher risk patients from patients with low and intermediate risk for disease progression in the Greek registry of IgAN.