BackgroundIt is currently unclear whether parenteral selenium supplementation should be recommended in the management of critically ill patients. Here we conducted a systematic review and meta-analysis to assess the efficacy of parenteral selenium supplementation on clinical outcomes.Methods/Principal FindingsRandomized trials investigating parenteral selenium supplementation administered in addition to standard of care to critically ill patients were included. CENTRAL, Medline, EMBASE, the Science Citation Index, and CINAHL were searched with complementary manual searches. The primary outcome was all-cause mortality. Trials published in any language were included. Two authors independently extracted data and assessed trial quality. A third author was consulted to resolve disagreements and for quality assurance. Twelve trials were included and meta-analysis was performed on nine trials that recruited critically ill septic patients. These comprised 965 participants in total. Of these, 148 patients (30.7%) in the treatment groups, and 180 patients (37.3%) in control groups died. Parenteral selenium treatment significantly reduced all-cause mortality in critically ill patients with sepsis (relative risk [RR] 0.83, 95% CI 0.70–0.99, p = 0.04, I2 = 0%). Subgroup analyses demonstrated that the administration schedule employing longer duration (RR 0.77, 95% CI 0.63–0.94, p = 0.01, I2 = 0%), loading boluses (RR 0.73, 95% CI 0.58–0.94, p = 0.01, I2 = 0%) or high-dose selenium treatment (RR 0.77, 95% CI 0.61–0.99, p = 0.04, I2 = 0%) might be associated with a lower mortality risk. There was no evidence of adverse events.Conclusions/SignificanceParenteral selenium supplementation reduces risk of mortality among critically ill patients with sepsis. Owing to the varied methodological quality of the studies, future high-quality randomized trials that directly focus on the effect of adequate-duration of parenteral selenium supplementation for severe septic patients are needed to confirm our results. Clinicians should consider these findings when treating this high-risk population.Systematic Review RegistrationPROSPERO 2011; CRD42011001768

Pylorus-resecting pancreaticoduodenectomy is a safe procedure associated with less severe and less frequent postoperative DGE than PpPD.

underlying mechanisms might be at least, partially related to reducing levels of inflammatory-related cytokines and to blocking an interaction between GSK3b-and RIP1K-mediated pathways.

Necroptosis initiation relies on the receptor-interacting protein 1 kinase (RIP1K). We recently reported that genetic and pharmacological inhibition of RIP1K produces protection against ischemic stroke-induced astrocytic injury. However, the role of RIP1K in ischemic stroke-induced formation of astrogliosis and glial scar remains unknown. Here, in a transient middle cerebral artery occlusion (tMCAO) rat model and an oxygen and glucose deprivation and reoxygenation (OGD/Re)-induced astrocytic injury model, we show that RIP1K was significantly elevated in the reactive astrocytes. Knockdown of RIP1K or delayed administration of RIP1K inhibitor Nec-1 down-regulated the glial scar markers, improved ischemic stroke-induced necrotic morphology and neurologic deficits, and reduced the volume of brain atrophy. Moreover, knockdown of RIP1K attenuated astrocytic cell death and proliferation and promoted neuronal axonal generation in a neuron and astrocyte co-culture system. Both vascular endothelial growth factor D (VEGF-D) and its receptor VEGFR-3 were elevated in the reactive astrocytes; simultaneously, VEGF-D was increased in the medium of astrocytes exposed to OGD/Re. Knockdown of RIP1K down-regulated VEGF-D gene and protein levels in the reactive astrocytes. Treatment with 400 ng/ml recombinant VEGF-D induced the formation of glial scar; conversely, the inhibitor of VEGFR-3 suppressed OGD/Re-induced glial scar formation. RIP3K and MLKL may be involved in glial scar formation. Taken together, these results suggest that RIP1K participates in the formation of astrogliosis and glial scar via impairment of normal astrocyte responses and enhancing the astrocytic VEGF-D/VEGFR-3 signaling pathways. Inhibition of RIP1K promotes the brain functional recovery partially via suppressing the formation of astrogliosis and glial scar. Graphical Abstract

Mannitol is effective in accomplishing short-term clinical goals, although hypertonic saline is associated with improved brain relaxation during craniotomy. Mannitol has a favorable safety profile although it can cause electrolyte abnormality and renal impairment. More research is needed to determine its impacts on long-term outcomes.