Severe bleeding in the ICU.

PURPOSE OF REVIEW: Severe bleeding events, which require blood transfusions, are a challenge faced by many critical care physicians on a daily basis. Current transfusion guidelines generally recommend rather strict transfusion thresholds and strategies, which can appear opposing to a patient in need for urgent transfusion at first sight. Moreover, applied guidelines are lacking evidence and specificity for the typical ICU patient population and its comorbidities. Transfusion decisions, which are pivotal for clinical outcome, are often unsatisfactorily based on hemoglobin levels only. RECENT FINDINGS: Recent publications generally support previous studies that a strict transfusion regimen is superior to a liberal one for the majority of cases. Newly developed and easily feasible techniques are currently in clinical trials and have the potential to become a valuable supplementation to hemoglobin-guided decision-making. In addition to the choice of the ideal transfusion strategy, physiological status and comorbidities were found to have a major impact on the outcome of severe bleedings in the ICU. SUMMARY: The body of evidence for ICU-specific transfusion guidelines is scarce. Critical care physicians should properly evaluate their patient's comorbidities and consider extended point-of-care testing for transfusion decisions in indistinct anemic situations. A strict transfusion strategy should, however, be applied whenever possible.

Lysyl oxidase-like 2 depletion is protective in age-associated vascular stiffening.

Vascular stiffening and its sequelae are major causes of morbidity and mortality in the elderly. The increasingly accepted concept of "smooth muscle cell (SMC) stiffness syndrome" along with matrix deposition has emerged in vascular biology to account for the mechanical phenotype of arterial aging, but the molecular targets remain elusive. In this study, using an unbiased proteomic analysis, we identified lysyl oxidase-like 2 (LOXL2) as a critical SMC mediator for age-associated vascular stiffening. We tested the hypothesis that loss of LOXL2 function is protective in aging-associated vascular stiffening. We determined that exogenous and endogenous nitric oxide markedly decreased LOXL2 abundance and activity in the extracellular matrix of isolated SMCs and LOXL2 endothelial cells suppress LOXL2 abundance in the aorta. In a longitudinal study, LOXL2+/- mice were protected from age-associated increase in pulse-wave velocity, an index of vascular stiffening, as occurred in littermate wild-type mice. Using isolated aortic segments, we found that LOXL2 mediates vascular stiffening in aging by promoting SMC stiffness, augmented SMC contractility, and vascular matrix deposition. Together, these studies establish LOXL2 as a nodal point for a new therapeutic approach to treat age-associated vascular stiffening. NEW & NOTEWORTHY Increased central vascular stiffness augments risk of major adverse cardiovascular events. Despite significant advances in understanding the genetic and molecular underpinnings of vascular stiffening, targeted therapy has remained elusive. Here, we show that lysyl oxidase-like 2 (LOXL2) drives vascular stiffening during aging by promoting matrix remodeling and vascular smooth muscle cell stiffening. Reduced LOXL2 expression protects mice from age-associated vascular stiffening and delays the onset of isolated systolic hypertension, a major consequence of stiffening.