IMPORTANCEIntravenous iron is recommended by many clinical guidelines based largely on its effectiveness in reducing anemia. However, the association with important safety outcomes, such as infection, remains uncertain. OBJECTIVE To examine the risk of infection associated with intravenous iron compared with oral iron or no iron. DATA SOURCES Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials (RCTs) from 1966 to January 31, 2021. Ongoing trials were sought from ClinicalTrials.gov, CENTRAL, and the World Health Organization International Clinical Trials Search Registry Platform. STUDY SELECTION Pairs of reviewers identified RCTs that compared intravenous iron with oral iron or no iron across all patient populations, excluding healthy volunteers. Nonrandomized studies published since January 1, 2007, were also included. A total of 312 full-text articles were assessed for eligibility. DATA EXTRACTION AND SYNTHESIS Data extraction and risk of bias assessments were performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) and Cochrane recommendations, and the quality of evidence was assessed using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Two reviewers extracted data independently. A random-effects model was used to synthesize data from RCTs. A narrative synthesis was performed to characterize the reporting of infection. MAIN OUTCOMES AND MEASURESThe primary outcome was risk of infection. Secondary outcomes included mortality, hospital length of stay, and changes in hemoglobin and red blood cell transfusion requirements. Measures of association were reported as risk ratios (RRs) or mean differences.RESULTS A total of 154 RCTs (32 920 participants) were included in the main analysis. Intravenous iron was associated with an increased risk of infection when compared with oral iron or no iron (RR, 1.17; 95% CI, 1.04-1.31; I 2 = 37%; moderate certainty of evidence). Intravenous iron also was associated with an increase in hemoglobin (mean difference, 0.57 g/dL; 95% CI, 0.50-0.64 g/dL; I 2 = 94%) and a reduction in the risk of requiring a red blood cell transfusion (RR, 0.93; 95% CI, 0.76-0.89; I 2 = 15%) when compared with oral iron or no iron. There was no evidence of an effect on mortality or hospital length of stay. (continued) Key Points Question In patients who require treatment with intravenous iron, what is the evidence that this intervention increases the risk of developing a new infection? Findings In this systematic review and meta-analysis of 154 randomized clinical trials that included 32 920 participants, intravenous iron was associated with an increased risk of infection. Meaning The results of this study suggest that, despite broad advocacy in clinical guidelines, intravenous iron may increase the risk of infection, which must be balanced with the potential benefits of treating anemia and reducing blood transfusion requirements.

BackgroundGuidelines to treat anaemia with intravenous (IV) iron have focused on elective surgical patients with little attention paid to those undergoing non-elective/emergency surgery. Whilst these patients may experience poor outcomes because of their presenting illness, observational data suggests that untreated anaemia may also be a contributing factor to poor outcomes. We conducted a systematic review to investigate the safety and efficacy of IV iron in patients undergoing non-elective surgery.MethodsWe followed a pre-defined review protocol and included randomised controlled trials (RCTs) in patients undergoing non-elective surgery who received IV iron. Primary outcomes were all-cause infection and mean difference in haemoglobin (Hb) at follow-up. Secondary outcomes included transfusion requirements, hospital length of stay (LOS), health-related quality of life (HRQoL), mortality and adverse events.ResultsThree RCTs (605 participants) were included in this systematic review of which two, in both hip fracture (HF) patients, provided data for meta-analysis. Both of these RCTs were at low risk of bias. We found no evidence of a difference in the risk of infection (RR 0.99, 95% CI 0.55 to 1.80, I2 = 9%) or in the Hb concentration at ‘short-term’ (≤ 7 days) follow-up (mean difference − 0.32 g/L, 95% CI − 3.28 to 2.64, I2 = 37%). IV iron did not reduce the risk of requiring a blood transfusion (RR 0.90, 95% CI 0.73 to 1.11, p = 0.46, I2 = 0%), and we observed no difference in mortality, LOS or adverse events. One RCT reported on HRQoL and found no difference between treatment arms.ConclusionWe found no conclusive evidence of an effect of IV iron on clinically important outcomes in patients undergoing non-elective surgery. Further adequately powered trials to evaluate its benefit in emergency surgical specialties with a high burden of anaemia are warranted.Trial registrationThis systematic review was registered on PROSPERO (CRD42018096288)Electronic supplementary materialThe online version of this article (10.1186/s13741-018-0109-4) contains supplementary material, which is available to authorized users.

Summary Pre‐operative anaemia is associated with poor outcomes after elective surgery but its relationship with outcomes after emergency surgery is unclear. We analysed National Emergency Laparotomy Audit data from 1 December 2013 to 30 November 2017, excluding laparotomy for haemorrhage. Anaemia was classified as ‘mild’ 129–110 g.l−1; ‘moderate’ 109–80 g.l−1; or ‘severe’ ≤ 79 g.l−1. The primary outcome was 90‐day mortality. Secondary outcomes were 30‐day mortality, return to theatre and postoperative hospital stay. The primary outcome was available for 86,763 patients, of whom 45,306 (52%) were anaemic. There were 12,667 (15%) deaths at 90 postoperative days and 9246 (11%) deaths at 30 postoperative days. Anaemia was associated with increased 90‐day and 30‐day mortality, odds ratio (95%CI): mild, 1.15 (1.09–1.21); moderate, 1.44 (1.36–1.52); and severe, 1.42 (1.24–1.63), p < 0.001 for all; mild, 1.07 (1.00–1.12), p = 0.030; moderate, 1.30 (1.21–1.38), p < 0.001; and severe, 1.22 (1.05–1.43), p = 0.010, respectively. All categories of anaemia were associated with prolonged hospital stay, adjusted coefficient (95%CI): mild, 1.31 (1.01–1.62); moderate, 3.41 (3.04–3.77); severe, 2.80 (1.83–3.77), p < 0.001 for all. Moderate and severe anaemia were associated with increased risk of return to the operating theatre, odds ratio (95%CI): moderate 1.13 (1.06–1.21), p < 0.001; and severe 1.23 (1.06–1.43), p = 0.006. Pre‐operative anaemia is common in patients undergoing emergency laparotomy and is associated with increased postoperative mortality and morbidity.

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Soybean oil consumption has increased greatly in the past half-century and is linked to obesity and diabetes. To test the hypothesis that soybean oil diet alters hypothalamic gene expression in conjunction with metabolic phenotype, we performed RNA sequencing analysis using male mice fed isocaloric, high-fat diets based on conventional soybean oil (high in linoleic acid, LA), a genetically modified, low-LA soybean oil (Plenish), and coconut oil (high in saturated fat, containing no LA). The 2 soybean oil diets had similar but nonidentical effects on the hypothalamic transcriptome, whereas the coconut oil diet had a negligible effect compared to a low-fat control diet. Dysregulated genes were associated with inflammation, neuroendocrine, neurochemical, and insulin signaling. Oxt was the only gene with metabolic, inflammation, and neurological relevance upregulated by both soybean oil diets compared to both control diets. Oxytocin immunoreactivity in the supraoptic and paraventricular nuclei of the hypothalamus was reduced, whereas plasma oxytocin and hypothalamic Oxt were increased. These central and peripheral effects of soybean oil diets were correlated with glucose intolerance but not body weight. Alterations in hypothalamic Oxt and plasma oxytocin were not observed in the coconut oil diet enriched in stigmasterol, a phytosterol found in soybean oil. We postulate that neither stigmasterol nor LA is responsible for effects of soybean oil diets on oxytocin and that Oxt messenger RNA levels could be associated with the diabetic state. Given the ubiquitous presence of soybean oil in the American diet, its observed effects on hypothalamic gene expression could have important public health ramifications.