Untargeted lipidomics uncovers lipid signatures distinguishing severe versus moderate forms of acutely decompensated cirrhosis

BACKGROUND AND AIM: Acutely decompensated of cirrhosis is a heterogeneous clinical entity associated with moderate mortality. In some patients, this condition develops quickly into a more often deadly acute-on-chronic liver failure (ACLF), in which other organs such as the kidneys or brain fail. The aim of this study was to characterize the blood lipidome in a large series of patients with cirrhosis and identify specific signatures associated with acute decompensation and ACLF development. METHODS: Serum untargeted lipidomics was performed in 561 patients with acutely decompensated (AD) cirrhosis (518 without and 43 with ACLF) (discovery cohort) and in 265 AD patients (128 without and 137 with ACLF) in whom serum samples were available to perform repeated measurements during the 28-day follow-up (validation cohort). Analyses were also performed in 78 AD patients included in a therapeutic albumin trial, 43 patients with compensated cirrhosis and 29 healthy subjects. RESULTS: The circulating lipid landscape associated with cirrhosis was characterized by a generalized suppression, which was more manifest during acute decompensation and in non-surviving patients. By computing discriminating accuracy and the variable importance projection score for each of the 223 annotated lipids, we identified a sphingomyelin fingerprint specific for AD cirrhosis and a distinct cholesteryl ester and lysophosphatidylcholine fingerprint for ACLF. Liver dysfunction, mainly, and infections were the principal net contributors to these fingerprints, which were dynamic and interchangeable between AD patients whose condition worsened to ACLF and those who improved. Notably, blood lysophosphatidylcholine levels increased in these patients after albumin therapy. CONCLUSIONS: Our findings provide insights into the lipid landscape associated with decompensation of cirrhosis and ACLF progression and identify unique noninvasive diagnostic biomarkers of advanced cirrhosis. LAY SUMMARY: Analysis of lipids in blood from patients with advanced cirrhosis reveals a general suppression of their levels in the circulation of these patients. A specific group of lipids known as sphingomyelins are useful to distinguish compensated from decompensated patients with cirrhosis. Another group of lipids designated cholesteryl esters further distinguish patients with decompensated patients who are at risk of developing organ failures

SoxD genes are required for adult neural stem cell activation

19 páginas, 6 figuras. Supplemental information can be found online at https://doi.org/10.1016/j. celrep.2022.110313.The adult neurogenic niche in the hippocampus is maintained through activation of reversibly quiescent neural stem cells (NSCs) with radial glia-like morphology (RGLs). Here, we show that the expression of SoxD transcription factors Sox5 and Sox6 is enriched in activated RGLs. Using inducible deletion of Sox5 or Sox6 in the adult mouse brain, we show that both genes are required for RGL activation and the generation of new neurons. Conversely, Sox5 overexpression in cultured NSCs interferes with entry in quiescence. Mechanistically, expression of the proneural protein Ascl1 (a key RGL regulator) is severely downregulated in SoxD-deficient RGLs, and Ascl1 transcription relies on conserved Sox motifs. Additionally, loss of Sox5 hinders the RGL activation driven by neurogenic stimuli such as environmental enrichment. Altogether, our data suggest that SoxD genes are key mediators in the transition of adult RGLs from quiescence to an activated mitotic state under physiological situations.This work was funded by grants to A.V.M. from the Spanish MICINN (SAF2017-85717-R, PID2020-112989RB-I00) and F. Alicia Koplowitz (2018) and to H.M. from the Spanish MICINN (SAF2015-70433-R, PID2019- 111225RB-I00) and PROMETEO/2018/055 from Generalitat ValencianaPeer reviewe

Artrodesis cervical con cajas de tantalio

Debida a su baja morbilidad y tasa de complicaciones, la discectomía cervical y fusión anterior ha ganado gran aceptación en los últimos 30 años en los que ha evolucionado desde su primera descripción. La esponja de tantalio se ha mostrado como un material ideal para fabricar cajas intersomáticas cervicales y lumbares debido a su alta porosidad, estabilidad y elasticidad parecida a la del hueso. Presentamos la técnica quirúrgica y nuestros resultados en los 12 primeros pacientes intervenidos en nuestra institución con un seguimiento mínimo de seis meses. No se ha recogido ninguna complicación intraoperatoria significativa. En ningún caso se empleó injerto óseo asociado a la caja. Los resultados clínicos han sido evaluados con los criterios de Odom y con las escalas de Oswestry y de Zung. La consolidación radiológica se ha considerado teniendo en cuenta los criterios de Cannada et al., y se han medido las diferencias del ángulo de Cobb y de la distancia interespinosas entre los espacios artrodesados en las radiografías dinámicas. No se ha observado ningún caso de pseudoartrosis. El implante ha mostrado una fácil y reproducible implantación quirúrgica y una rápida integración radiológica. La caja de tantalio para la artrodesis cervical representa un avance real, sin embargo, aún es perfectible desde el punto de vista técnico

Plasma rico en plaquetas. Análisis coparativo de cuatro presentaciones comerciales

Los factores de crecimiento liberados desde las plaquetas y células de la serie blanca constituyen la orden inicial que desencadena la reparación tisular. Extraídos del propio paciente y aplicados en la zona lesionada, estos factores pueden actuar como estimuladoeres de la curación de las lesiones y heridas y constituir una importante herramienta terapéutica que acelera la curación de nuestros pacientes. En este artículo se comparan, desde el punto de vista técnico, cuatro sistemas diferentes de producción de plasma rico en plaquetas. Estos sistemas son: PRGF, AGF, PCCS y GPS. Todos ellos son capaces de garantizar la producción de un concentrado de plaquetas con una concentración mínima de un millón por microlito, por lo que los consideramos plenamente válidos. Las diferencias técnicas más importantes son: el volumen de plasma rico en plaquetas obtenible y la facilidad de manejo en quirófano