Regulators impeding erythropoiesis following iron supplementation in a clinically relevant rat model of iron deficiency anemia with inflammation.

AIMS: While elevated hepcidin levels with inflammation have been postulated as a putative mechanism hindering effective erythropoiesis after intravenous (IV) iron therapy in anemic patients undergoing surgery, little is known about the concomitant changes in other major regulators affecting erythropoiesis. This study investigated the activities of relevant regulators after iron replenishment in a rat model of iron deficiency anemia with inflammation. MAIN METHODS: Inflammation was induced by administration of complete Freund's adjuvant (CFA) in male Sprague-Dawley rats. After 2 weeks of CFA treatment, the rats received IV iron (CFA­iron) or saline (CFA-saline). The control group received saline instead of CFA and iron (saline-saline). At 1, 3, and 10 days after iron or saline treatment, inflammatory cytokines, oxidative markers, iron profiles, hepcidin, erythropoietin (EPO), erythroferrone (ERFE), fibroblast growth factor 23 (FGF 23), and expression of mRNA and proteins in the liver involved in hepcidin signaling pathways were measured. KEY FINDINGS: CFA treatment and iron restriction decreased hemoglobin and serum iron levels, significantly increasing inflammatory and oxidative markers. Iron supplementation did not restore hemoglobin levels despite improved iron profiles. CFA injections increased hepcidin and FGF 23 levels and decreased EPO and ERFE levels, which further intensified after iron supplementation with concomitantly elevated levels of oxidative stress and inflammatory markers. SIGNIFICANCE: Under inflammatory conditions, IV iron administration exacerbated inflammatory and oxidative stress and did not resolve anemia, even under iron deficiency conditions. Iron therapy exerted adverse influences on the changes in key regulators toward impeding erythropoiesis that was already impeded by inflammation.

Preoperative Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, and Mean Platelet Volume as Predictors of 1-Year Mortality in Patients Undergoing an Open Repair of Abdominal Aortic Aneurysms: A Retrospective Study.

OBJECTIVES: To investigate if preoperative neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), or mean platelet volume (MPV) could be used to predict 1-year mortality in patients undergoing open abdominal aortic aneurysm (AAA) repair. METHODS: We retrospectively reviewed 382 patients who underwent open AAA repair between January 2008 and July 2019. We divided the patients into two groups based on 1-year mortality and compared the preoperative NLR, PLR, and MPV. The patients were then classified into tertiles based on their preoperative NLR (first tertile: <2.41 (n = 111); second tertile: 2.41 ≤ NLR ≤ 6.07 (n = 111); and third tertile: >6.07 (n = 112)). We compared the incidence of mortality and morbidity across the aforementioned tertiles. We performed a stepwise logistic regression analysis to evaluate the predictors for mortality. An additional subgroup analysis was performed by dividing the cases into non-ruptured and ruptured cases. RESULTS: The preoperative NLR was significantly higher in the non-survivor group than in the survivor group (10.53 ± 7.60 vs. 5.76 ± 6.44, respectively, p = 0.003). The PLR and MPV were similar between the groups (145.35 ± 91.11 vs. 154.20 ± 113.19, p = 0.626, 9.38 ± 1.20 vs. 9.11 ± 1.39, p = 0.267, respectively). The incidence of 1-year mortality was 2.7%, 9.0%, and 14.3% in the first, second, and third NLR tertiles, respectively (p = 0.009). Higher NLR (odds ratio 1.085, 95% confidence interval 1.016-1.159, p = 0.015) and ruptured AAA (odds ratio 2.706, 95% confidence interval 1.097-6.673, p = 0.031) were the independent predictors of 1-year mortality in all patients. Moreover, the preoperative NLR was significantly higher in the ruptured AAA than in the non-ruptured AAA group (11.17 ± 7.90 vs. 4.10 ± 4.75, p < 0.001). In subgroup analysis, preoperative NLR (odds ratio 1.144, 95% confidence interval 1.031-1.271, p = 0.012) and PLR (odds ratio 0.986, 95% confidence interval 16 0.975-0.998, p = 0.017) was an independent predictor for 1-year mortality in ruptured cases. CONCLUSIONS: We demonstrated an independent relationship between the preoperative NLR and 1-year mortality in patients undergoing open AAA repair, besides PLR and MPV. Furthermore, the NLR and PLR had predictive power for 1-year mortality in ruptured cases.