RESUMEN
Partial or complete imaging resolution of left ventricular (LV) systolic dysfunction in patients with heart failure with reduced ejection fraction (HFrEF) has gone by many names in the past few decades, including LV recovery, remission, reverse remodeling, and, most recently, improvement. This phenomenon has been described in a variety of clinical scenarios, including removal of an acute myocardial insult, unloading with durable LV assist devices, and treatment with various devices as well as pharmacotherapies, termed guideline-directed medical therapy (GDMT). Irrespective of definition, systolic improvement is associated with improved clinical outcomes compared to persistent systolic dysfunction. In the past few years, systolic improvement has been distinguished from HFrEF as a new clinical entity referred to as HF with improved EF (HFimpEF). Given the relative novelty of this condition, there is a paucity of data with regard to the clinical trajectory and management of this population. In this review, we describe the history of myocardial improvement terminology and explore notable findings that have led to the delineation of HFimpEF. Additionally, we highlight the importance of understanding LV trajectory and the potential opportunity for new GDMT management for clinicians when treating patients with HFimpEF.
Asunto(s)
Insuficiencia Cardíaca , Recuperación de la Función , Volumen Sistólico , Disfunción Ventricular Izquierda , Función Ventricular Izquierda , Remodelación Ventricular , Humanos , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/diagnóstico por imagen , Resultado del Tratamiento , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/terapia , Disfunción Ventricular Izquierda/epidemiología , Prevalencia , Terminología como Asunto , Fármacos Cardiovasculares/uso terapéutico , Estado Funcional , Valor Predictivo de las PruebasRESUMEN
IMPORTANCE: Ultrasound bladder scanners may provide a less invasive method to measure postpartum urinary volume, but their accuracy must be validated. OBJECTIVE: The objective of this study was to evaluate the accuracy of a bladder scanner in measuring bladder volumes in postpartum women. The secondary objective was to evaluate the effect of obesity on scanner accuracy. STUDY DESIGN: This prospective cohort study included women older than 18 years who gave birth vaginally at term gestation. After delivery, we obtained 3 sequential measurements of the bladder volume using an ultrasound bladder scanner. We then measured true bladder volume by transurethral catheterization. The primary outcome was the absolute difference between the bladder scanner volume and the catheterized volume. A Wilcoxon signed-rank test was used to compare absolute median difference between the bladder scan volume and true catheter volume. Repeated-measures analysis of variance and linear regression were used to evaluate the effect of obesity on the accuracy of the bladder scanner. RESULTS: We enrolled 70 patients (61.4% nulliparous, 38.6% multiparous). One delivery was vacuum-assisted, 4 were forceps-assisted, and 65 were spontaneous vaginal. The median age was 34 years, and median body mass index was 30.5. Median difference between bladder scanner and catheter volume was 42.7 mL (P < 0.001), with the scanner underestimating true volume 82.9% of the time. The scanner was less accurate in patients with a body mass index ≥ 30 (P = 0.001). CONCLUSIONS: The bladder scanner is less accurate than catheterized urine volume. However, the median difference between the bladder scanner and the catheterized volume is 42.7 mL, making it suitable for clinical use. Accuracy deteriorates in obese patients.
Asunto(s)
Periodo Posparto , Vejiga Urinaria , Humanos , Femenino , Embarazo , Adulto , Vejiga Urinaria/diagnóstico por imagen , Estudios Prospectivos , Parto , Obesidad/diagnóstico por imagenRESUMEN
Epithelial-to-mesenchymal transition (EMT) is a transcriptionally governed process by which cancer cells establish a front-rear polarity axis that facilitates motility and invasion. Dynamic assembly of focal adhesions and other actin-based cytoskeletal structures on the leading edge of motile cells requires precise spatial and temporal control of protein trafficking. Yet, the way in which EMT-activating transcriptional programs interface with vesicular trafficking networks that effect cell polarity change remains unclear. Here, by utilizing multiple approaches to assess vesicular transport dynamics through endocytic recycling and retrograde trafficking pathways in lung adenocarcinoma cells at distinct positions on the EMT spectrum, we find that the EMT-activating transcription factor ZEB1 accelerates endocytosis and intracellular trafficking of plasma membrane-bound proteins. ZEB1 drives turnover of the MET receptor tyrosine kinase by hastening receptor endocytosis and transport to the lysosomal compartment for degradation. ZEB1 relieves a plus-end-directed microtubule-dependent kinesin motor protein (KIF13A) and a clathrin-associated adaptor protein complex subunit (AP1S2) from microRNA-dependent silencing, thereby accelerating cargo transport through the endocytic recycling and retrograde vesicular pathways, respectively. Depletion of KIF13A or AP1S2 mitigates ZEB1-dependent focal adhesion dynamics, front-rear axis polarization, and cancer cell motility. Thus, ZEB1-dependent transcriptional networks govern vesicular trafficking dynamics to effect cell polarity change.
Asunto(s)
Endosomas/metabolismo , Transición Epitelial-Mesenquimal/genética , Transición Epitelial-Mesenquimal/fisiología , Neoplasias Pulmonares/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Actinas/metabolismo , Subunidades sigma de Complejo de Proteína Adaptadora , Adenocarcinoma del Pulmón/metabolismo , Línea Celular Tumoral , Polaridad Celular , Citoesqueleto/metabolismo , Endocitosis , Adhesiones Focales/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Cinesinas , Neoplasias Pulmonares/genética , Proteínas de la Membrana/metabolismo , MicroARNs/metabolismo , Metástasis de la NeoplasiaRESUMEN
Heightened secretion of protumorigenic effector proteins is a feature of malignant cells. Yet, the molecular underpinnings and therapeutic implications of this feature remain unclear. Here, we identify a chromosome 1q region that is frequently amplified in diverse cancer types and encodes multiple regulators of secretory vesicle biogenesis and trafficking, including the Golgi-dedicated enzyme phosphatidylinositol (PI)-4-kinase IIIß (PI4KIIIß). Molecular, biochemical, and cell biological studies show that PI4KIIIß-derived PI-4-phosphate (PI4P) synthesis enhances secretion and accelerates lung adenocarcinoma progression by activating Golgi phosphoprotein 3 (GOLPH3)-dependent vesicular release from the Golgi. PI4KIIIß-dependent secreted factors maintain 1q-amplified cancer cell survival and influence prometastatic processes in the tumor microenvironment. Disruption of this functional circuitry in 1q-amplified cancer cells with selective PI4KIIIß antagonists induces apoptosis and suppresses tumor growth and metastasis. These results support a model in which chromosome 1q amplifications create a dependency on PI4KIIIß-dependent secretion for cancer cell survival and tumor progression.