RESUMO
In sub-Saharan Africa, multidrug-resistant non-typhoidal Salmonella serovars are a common cause of fatal bloodstream infection. Malnutrition is a predisposing factor, but the underlying mechanisms are unknown. Here we show that vitamin A deficiency, one of the most prevalent micronutrient deficits afflicting African children, increases susceptibility to disseminated non-typhoidal Salmonella disease in mice and impairs terminal neutrophil maturation. Immature neutrophils had reduced expression of Slc11a1, a gene that encodes a metal ion transporter generally thought to restrict pathogen growth in macrophages. Adoptive transfer of SLC11A1-proficient neutrophils, but not SLC11A1-deficient neutrophils, reduced systemic Salmonella burden in Slc11a1-/- mice or mice with vitamin A deficiency. Loss of terminal granulopoiesis regulator CCAAT/enhancer-binding protein ϵ (C/EBPϵ) also decreased neutrophil-mediated control of Salmonella, but not that mediated by peritoneal macrophages. Susceptibility to infection increased in Cebpe-/- Slc11a1+/+ mice compared with wild-type controls, in an Slc11a1-expression-dependent manner. These data suggest that SLC11A1 deficiency impairs Salmonella control in part by blunting neutrophil-mediated defence.
Assuntos
Salmonelose Animal , Deficiência de Vitamina A , Criança , Camundongos , Humanos , Animais , Neutrófilos , Salmonella , MacrófagosRESUMO
PURPOSE: To analyze the effect of a patient's renal failure status on acute outcomes after lower extremity endovascular interventions for peripheral artery disease. MATERIALS AND METHODS: A retrospective analysis of the American College of Surgery National Surgical Quality Improvement Program database from 2014 to 2017 was conducted. Patients were included based on current procedural terminology codes. They were divided into renal failure cohorts. Six thousand seven hundred and sixty-five patients were included in the analysis, 11.0% of whom had renal failure. A univariate analysis was performed using chi-squared test or Fischer's exact test as appropriate. Multivariate logistic regression models were constructed, while controlling for relevant patient factors, to identify the effect of renal failure on several outcomes of interest after the intervention. A sensitivity analysis was performed with a propensity score-matched cohort. RESULTS: Patients with renal failure were more likely to have infrapopliteal interventions (38.0% vs 20.9%), critical limb ischemia with tissue loss (73.5% vs 38.9%), diabetes (70.9% vs 52.3%), preoperative wound infection (59.2% vs 30.7%), mortality (5.1% vs 1.3%), prolonged hospital stay (68.5% vs 46.5%), transfusion after the intervention (13.3% vs 9.1%), reoperation (18.3% vs 9.5%), and readmission (24.9% vs 12.6%), compared to patients without renal failure. The multivariate analysis found renal failure to be significant for mortality (odds ratio [OR] = 4.11, 95% confidence interval [CI] = 2.71-6.24), any complication (OR = 2.03, 95% CI = 1.72-2.39), extended length of stay (OR = 1.53, 95% CI = 1.28-1.83), sepsis (OR = 2.37, 95% CI = 1.60-3.51), readmission (OR = 1.89, 95% CI = 1.57-2.29), reoperation (OR = 1.84, 95% CI = 1.48-2.27), major adverse cardiovascular event (OR = 3.50, 95% CI = 2.54-4.84), and major adverse limb event (OR = 1.97, 95% CI = 1.55-2.51). P value was <.001 unless otherwise noted. CONCLUSIONS: Renal failure before the intervention places patients at a significantly elevated risk of morbidity and mortality following endovascular revascularization procedures for peripheral artery disease.