The Iron Revolution: Keeping Abreast of The Developments in Iron Therapy

Abstract Background Large randomized clinical trials have demonstrated that intravenous (IV) iron therapy in iron-deficient patients with heart failure with reduced ejection fraction (HFrEF) brings clinical benefits related to symptoms of the disease and exercise capacity. Mechanisms underlying beneficial effects of such repletion are still the subject of interest as this is not solely related to improved haematopoiesis (IV iron works also in non-anaemic subjects). In patients with chronic heart failure iron deficiency (ID) is linked with inflammatory processess but data regarding the impact of IV iron on inflammation is scarce. Purposes We evaluated whether IV iron therapy affects circulating biomarkers of pro-inflammatory state in men with HFrEF and concomitant ID. Methods This is the sub-analysis of the study to investigate the effects of IV ferric carboxymaltose (FCM) on the functioning of skeletal muscles in men with HFrEF. For the purposes of current research we analyzed data of 20 men with HFrEF (median age 68 (62, 75 – in brackets interquartile ranges, respectively) years, LVEF: 30 (25, 35) %, ischaemic HF aetiology: 85%, NYHA class I/II/III: 30%/50%/20%) and ID (definition according to ESC guidelines - ferritin <100 ng/mL, or ferritin 100–299 ng/mL with transferrin saturation [TSAT] <20%) who were randomized in a 1:1 ratio to receive either the 24-week therapy with IV FCM (dosing scheme as in the CONFIRM-HF trial) or saline (controls). The study was double-blinded. We used ELISA to evaluate different circulating pro-inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], interleukin 1 beta [IL-1β], interleukin 22 [IL-22]) at baseline and week 24. Results IV FCM therapy repleted iron stores in men with HFrEF as reflected by an increase in serum ferritin and TSAT, which was not seen in a control group. IV FCM therapy (as well as the saline administration) affected neither haemoglobin concentration nor parameters reflecting iron stores in red cells. Baseline serum ferritin was not related to hs-CRP, TNF-α, IL-6, IL-1β, and IL-22 (all p>0.23). Baseline TSAT was related to hs-CRP (r=−0.47, p=0.02) but not other inflammatory biomarkers. Levels of hs-CRP, TNF-α, IL-6, IL-1β, and IL-22 at week 0 were similar in subjects who received IV iron and controls (all p>0.22). Change from week 0 to week 24 adjusted for baseline value (delta W24-W0 as the percentage of W0) regarding IL-22 was lower in an active treatment arm as compared with saline (p=0.049) and there was a trend towards lower delta TNF-α in FCM group compared to saline (p=0.067). These findings were not valid for other measured pro-inflammatory biomarkers. Conclusions In men with HFrEF and concomitant ID intravenous iron therapy with FCM affects biomarkers of pro-inflammatory state. Clinical relevance of this finding requires further translational research. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This research was funded by the National Science Centre (Poland) grant allocated on the basis of the decision number DEC-2012/05/E/NZ5/00590

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Preemptive intravenous iron therapy versus autologous whole blood therapy for early postoperative hemoglobin level in patients undergoing bimaxillary orthognathic surgery: a prospective randomized noninferiority trial

BMC Oral Health ◽

10.1186/s12903-020-01359-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Min Suk Chae ◽

Mihyun Lee ◽

Min Ho Choi ◽

Je Uk Park ◽

Misun Park ◽

...

Keyword(s):

Blood Transfusion ◽

Blood Group ◽

Whole Blood ◽

Orthognathic Surgery ◽

Hemoglobin Level ◽

Iron Therapy ◽

Iron Group ◽

Autologous Whole Blood ◽

Bimaxillary Orthognathic Surgery ◽

Iv Iron

Abstract Background Previous studies have reported the efficacy and safety of intravenous (IV) iron therapy during the perioperative period as an alternative and adjunct to allogeneic blood transfusion. Preemptive IV iron therapy provides noninferior hemoglobin levels on postoperative day (POD) 1 compared to autologous whole blood therapy (AWBT) in healthy patients who had undergone bimaxillary orthognathic surgery. Methods This was a prospective, patient-randomized, noninferiority trial. After excluding 2 patients, 64 patients were divided into two groups: the IV iron therapy group (patients received IV iron infusion 4 weeks before surgery; n = 32) and the AWBT group (2 units of autologous whole blood were collected 4 and 2 weeks before surgery; n = 32). The primary outcome was hemoglobin level on POD 1 and the prespecified noninferiority limit was − 1 g/dL. Results Baseline data were comparable, including hemoglobin and iron levels, between the two groups. Immediately before surgery, the levels of hemoglobin, iron, and ferritin were higher in the IV iron group than in the AWBT group. The mean treatment difference (iron group—whole blood group) in hemoglobin level on POD 1 between the two groups was 0.09 (95% CI = − 0.83 to 1.0). As the lower limit of the 95% CI (− 0.83) was higher than the prespecified noninferiority margin (δ = − 1), noninferiority was established. On POD 2, the hemoglobin level became lower in the iron group, which eventually led to greater requirement of allogeneic blood transfusion compared to the whole blood group. However, the iron group did not require allogeneic blood transfusion during or early after surgery, and the whole blood group showed continuously higher incidence of overt iron deficiency compared to the iron group. Conclusion As collection of autologous whole blood caused overt iron loss and anemia before surgery and intraoperative transfusion of whole blood was not able to prevent the occurrence of persistent iron deficiency after surgery, IV iron therapy was found to have potential benefits for iron homeostasis and subsequent erythropoiesis in healthy patients early after bimaxillary orthognathic surgery. Trial registration: Clinical Research Information Service, Republic of Korea, approval number: KCT0003680 on March 27, 2019. https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=15769&sLeft=2&ltype=my&rtype=my.

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Oral and Intravenous Iron Therapy Differentially Alter the On- and Off-Tumor Microbiota in Anemic Colorectal Cancer Patients

Cancers ◽

10.3390/cancers13061341 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1341

Author(s):

Oliver Phipps ◽

Hafid O. Al-Hassi ◽

Mohammed N. Quraishi ◽

Edward A. Dickson ◽

Jonathan Segal ◽

...

Keyword(s):

Colorectal Cancer ◽

Ferrous Sulphate ◽

Intravenous Iron ◽

Oral Iron ◽

Iron Therapy ◽

Deficiency Anemia ◽

Ferric Carboxymaltose ◽

Β Diversity ◽

Post Surgery ◽

Intravenous Iron Therapy

Iron deficiency anemia is a common complication of colorectal cancer and may require iron therapy. Oral iron can increase the iron available to gut bacteria and may alter the colonic microbiota. We performed an intervention study to compare oral and intravenous iron therapy on the colonic tumor-associated (on-tumor) and paired non-tumor-associated adjacent (off-tumor) microbiota. Anemic patients with colorectal adenocarcinoma received either oral ferrous sulphate (n = 16) or intravenous ferric carboxymaltose (n = 24). On- and off-tumor biopsies were obtained post-surgery and microbial profiling was performed using 16S ribosomal RNA analysis. Off-tumor α- and β-diversity were significantly different between iron treatment groups. No differences in on-tumor diversity were observed. Off-tumor microbiota of oral iron-treated patients showed higher abundances of the orders Clostridiales, Cytophagales, and Anaeroplasmatales compared to intravenous iron-treated patients. The on-tumor microbiota was enriched with the orders Lactobacillales and Alteromonadales in the oral and intravenous iron groups, respectively. The on- and off-tumor microbiota associated with intravenous iron-treated patients infers increased abundances of enzymes involved in iron sequestration and anti-inflammatory/oncogenic metabolite production, compared to oral iron-treated patients. Collectively, this suggests that intravenous iron may be a more appropriate therapy to limit adverse microbial outcomes compared to oral iron.

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