Background and purpose Bioavailability studies and observational evidence suggest that heme iron (HI) may have greater impact on iron status indicators compared with non-heme iron (NHI). This systematic review and meta-analysis aimed to review the current evidence on the effect of the administration of HI compared with NHI for improving iron status in non-hospitalized population groups. Methods We searched Pubmed, CENTRAL, Scopus, Web of Science, and LILACS from inception to July 2024. There was no language restriction or exclusion based on age or iron status. Only randomized controlled trials comparing HI with NHI were considered. A random-effects meta-analysis was performed to compare the effect of treatments for iron status indicators and total side effects (including gastrointestinal side effects). We measured the certainty of the evidence (CoE) using GRADE assessment. Results After screening 3097 articles, 13 studies were included. Most of the interventions used HI in low doses combined with NHI. The meta-analysis showed higher hemoglobin increases in children with anemia or low iron stores receiving HI (MD 1.06 g/dL; 95% CI: 0.34; 1.78; CoE: very low). No statistically significant difference between interventions were found for any iron status indicator in the other population subgroups (CoE: very low). Participants receiving HI had a 38% relative risk reduction of total side effects compared to NHI (RR 0.62; 95% CI 0.40; 0.96; CoE: very low). Conclusion The current evidence comparing HI with NHI is very limited, preliminary findings suggest that interventions using HI may result in fewer side effects and may be superior in children with iron deficiency or anemia. However, given the very low certainty of the evidence, these results need further investigation through high-quality clinical trials. Protocol registration CRD42023483157.

Background and Objectives: High-grade gliomas (HGGs) are aggressive primary brain tumors with a poor prognosis despite multimodal treatment. The anesthetic technique used during surgery may influence tumor progression and survival, but its role in HGGs remains unclear. This meta-analysis evaluated the effect of total intravenous anesthesia (TIVA) versus inhalational anesthesia (INHA) on overall survival (OS) and progression-free survival (PFS) in HGG patients. Materials and Methods: A systematic search was conducted in PubMed, Scopus, and Cochrane databases for studies assessing the impact of TIVA versus INHA on OS and PFS in HGG patients. Statistical analysis was performed using R version 4.3.1. Heterogeneity across studies was quantified using the Cochrane Q test alongside the I² statistic. A random-effects model was employed to derive the pooled hazard ratios (HRs). Results: A total of five studies involving 827 participants (mean age 58 years, mean females 38%) were included, of whom 406 (49%) received TIVA. No statistically significant differences were observed in OS (HR 0.77; 95% CI [0.58–1.02]; p = 0.07; I² = 67%) or PFS (HR 0.88; 95% CI [0.70–1.10]; p = 0.27; I² = 51%) between the groups. A subgroup analysis revealed that TIVA was associated with improved OS in patients with grade IV tumors (HR 0.70; 95% CI [0.51–0.96]; p = 0.03), while no significant effect was observed in the mixed grade III–IV subgroup. However, the test for subgroup differences was not statistically significant (p = 0.0669), and this finding should be interpreted with caution. No significant differences were observed in median OS or PFS, or in single-arm meta-analyses. Conclusions: This meta-analysis found no statistically significant differences in overall or progression-free survival between TIVA and INHA in patients undergoing surgery for HGGs. Although a subgroup analysis suggested a possible survival advantage of TIVA in grade IV tumors, the lack of a statistically significant subgroup difference test limits the strength of this finding. Further investigation is needed to determine whether anesthetic technique influences outcomes in this subgroup.