Bevacizumab prevents tumor recurrence and metastasis promoted by nab-paclitaxel activation of NF-κB pathway. Combination therapy with high-dosed nab-paclitaxel demonstrates the potential to eradicate advanced primary tumors and preexisting metastases. These findings strongly support translating this regimen into clinics.
Purpose of review-This review aims to describe the relationship between nutrition and the gut microbiome in critical illness. Recent findings-Critical illness disrupts not only cells of human origin but also the intestinal microbiome, with a decrease in bacterial diversity and transformation into a pathobiome. Under basal conditions, nutrition profoundly alters microbial composition with significant salutatory effects on human health. In critical illness, enteral nutrition is recommended and has theoretical (but not proven) advantages towards improved inner microbial health and diminution of bacterial translocation. Dietary supplements such as probiotics and fiber have been shown to improve microbial derangements in health. However, their impact on the microbiome in critical illness is unclear and while they may have some beneficial effects on patient-centric outcomes, they do not alter mortality. The precise mechanisms of how nutrition and dietary supplements modulate the gut microbiome remain to be determined. Summary-Nutrition and supplements such as probiotics appear to play a significant role in modulating the microbiome in health, yet the relationship in critical illness is unclear. Further investigation is required to determine the mechanistic determinants of the impact of nutrition on the microbiome in critical illness and the potential clinical implications of this.
Mortality is higher in septic patients with a history of alcohol use disorder than in septic patients without a history of chronic alcohol usage. We have previously described a model of chronic alcohol ingestion followed by sepsis from cecal ligation and puncture in which alcohol-fed septic mice have higher mortality than water-fed septic mice, associated with altered gut integrity and increased production of TNF and IFNγ by splenic CD4 T cells without alterations in CD8 T cell function. The purpose of this study was to determine whether this represents a common host response to the combination of alcohol and sepsis by creating a new model in which mice with chronic alcohol ingestion were subjected to a different model of sepsis. C57Bl/6 mice were randomized to receive either alcohol or water for 12 weeks and then subjected to Pseudomonas aeruginosa pneumonia. Mice were sacrificed either 24 hours after the onset of sepsis or followed for survival. Alcohol-fed septic mice had significantly higher 7-day mortality than water-fed septic mice (96% vs 58%). This was associated with a 5-fold increase in intestinal apoptosis in alcohol-fed septic animals, accompanied by an increase in the pro-apoptotic protein Bax. Serum IL-6 levels were higher and IL-2 levels were lower in alcohol-fed septic mice. In contrast, CD8 T cell frequency was lower in alcohol-fed mice than water-fed septic mice, associated with increased production of IFNγ and TNF in stimulated splenocytes. No significant differences were noted in CD4 T cells, lung injury or bacteremia. Mice with chronic alcohol ingestion thus have increased mortality regardless of their septic insult, associated with changes in both the gut and the immune system.
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