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Background and Aims: Intravenous iron therapies contain iron-carbohydrate complexes, designed to ensure iron becomes bioavailable via the intermediary of spleen and liver reticuloendothelial macrophages. How other tissues obtain and handle this iron remains unknown. This study addresses this question in the context of the heart., Methods: A prospective observational study was conducted in 12 patients receiving ferric carboxymaltose (FCM) for iron deficiency. Myocardial, spleen, and liver magnetic resonance relaxation times and plasma iron markers were collected longitudinally. To examine the handling of iron taken up by the myocardium, intracellular labile iron pool (LIP) was imaged in FCM-treated mice and cells., Results: In patients, myocardial relaxation time T1 dropped maximally 3 h post-FCM, remaining low 42 days later, while splenic T1 dropped maximally at 14 days, recovering by 42 days. In plasma, non-transferrin-bound iron (NTBI) peaked at 3 h, while ferritin peaked at 14 days. Changes in liver T1 diverged among patients. In mice, myocardial LIP rose 1 h and remained elevated 42 days after FCM. In cardiomyocytes, FCM exposure raised LIP rapidly. This was prevented by inhibitors of NTBI transporters T-type and L-type calcium channels and divalent metal transporter 1., Conclusions: Intravenous iron therapy with FCM delivers iron to the myocardium rapidly through NTBI transporters, independently of reticuloendothelial macrophages. This iron remains labile for weeks, reflecting the myocardium's limited iron storage capacity. These findings challenge current notions of how the heart obtains iron from these therapies and highlight the potential for long-term dosing to cause cumulative iron build-up in the heart., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Iron oxides, antioxidants, and pigmentary titanium dioxide are sunscreen additive ingredients that enhance visible light protection, reduce associated hyperpigmentation, and protect against certain photosensitive dermatoses There are currently no standardized recommendations for visible light protection with these additive ingredients, leading to varied clinical recommendations., Objectives: This study aimed to evaluate dermatology practitioners' counseling practices for visible light protection., Methods: An electronic survey was distributed to dermatology practitioners. Survey responses were compiled for analysis, and statistical significance was calculated using a standard 95% confidence interval., Results: 91.68% of 974 respondents actively counsel patients about visible light protection, primarily emphasizing its role in exacerbating pigmentation in patients with melanin-rich skin (70.92%). Of these, 10.34% recommended sunscreens with visible light protective additive ingredients specifically for patients with melanin-rich skin, and 48.89% recommended them for managing melasma or post-inflammatory hyperpigmentation. Iron oxide additive ingredients were most frequently recommended (90.92%), followed by antioxidants (69.08%) and pigmentary TiO2, (58.85%). 8.32% of respondents reported not counseling patients about visible light protection, with major reasons encompassing the lack of standardized guidelines (50.62%), challenges in recommending suitably tinted sunscreens (27.16%), limited availability of sunscreen options (23.46%), and insufficient supportive data (18.52%)., Conclusion: There is a need for increased education and awareness regarding visible light protection strategies and the identification of patients who may benefit the most from a targeted photoprotective strategy. Establishing standardized guidelines and broadening the availability of sunscreen options conferring visible light protection may help address these gaps. J Drugs Dermatol. 2024;23(11):965-971. doi:10.36849/JDD.8159.

Introduction: Intravenous (IV) iron is the recommended treatment for patients with iron deficiency anemia (IDA) unresponsive to oral iron treatment, in whom oral iron is contraindicated, or where rapid iron replenishment is required. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are high-dose, rapid-infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), which showed significantly higher incidence of hypophosphatemia after administration of FCM than FDI. The present study objective was to evaluate the cost-utility of FDI versus FCM in a population of patients with IDA in China., Methods: A previously-published patient-level simulation model was used to model the cost-utility of FDI versus FCM in China. The number of infusions of FDI and FCM was modeled based on the approved posology of the respective formulations using simplified tables of iron need in a population of patients with body weight and hemoglobin levels informed by a Chinese RCT of FCM. Data on the incidence of hypophosphatemia was obtained from the PHOSPHARE-IDA RCT, while data on disease-related quality of life were obtained from SF-36v2 data from the PHOSPHARE-IBD RCT., Results: Over the 5-year time horizon, patients received 3.98 courses of iron treatment on average, requiring 0.90 fewer infusions of FDI than FCM (7.69 vs. 6.79). This resulted in iron procurement and administration cost savings of renminbi (RMB) 206 with FDI (RMB 3,519 vs. RMB 3,312). Reduced incidence of hypophosphatemia-related fatigue resulted in an increase of 0.07 quality-adjusted life years and further cost savings of RMB 782 over 5 years, driven by reduced need for phosphate testing and replenishment. FDI was therefore the dominant intervention., Conclusions: The results showed that FDI would improve patient quality of life and reduce direct healthcare expenditure versus FCM in patients with IDA in China., (© 2024. The Author(s).)

Poultry is a ubiquitous and highly sought-after protein source valued for its accessibility, notable protein content, and lack of religious constraints. However, the demand for poultry has resulted in a surge in intensive production practices. The transition from subsistence agricultural practices to intensive food production resulted in the widespread adoption of antibiotics for both therapeutic and economic purposes. These interventions were intended to enhance meat yield, promote bird health, and enhance cost-effectiveness of production. However, this inadvertently contributed to the rise of antimicrobial resistance (AMR). Therefore, the need to explore alternative approaches to mitigate the problems associated with AMR has become increasingly pressing. In response, metal-based compounds have emerged as a promising substitute to conventional antibiotics. In this study, the effects of a water soluble metallo-antimicrobial supplement, ferric sillen core-linked polymer (FSCLP), on body weight gain, feed conversion, water intake, volatile fatty acid (VFA) production, cecal microbiome and intestinal morphology in broilers was examined. The findings of this study suggested that the addition of the FSCLP resulted in better bird performance, even during a period of heat stress. Volatile fatty acids analysis of cecal contents indicated that there were significantly higher levels (p < 0.05) of butyric and valeric acids. Cecal microbiome analysis confirmed significantly lower abundance (p < 0.05) of Proteobacteria (e.g., E. coli) and a significantly greater abundance of VFA-producing bacteria such as Intestinimonas butyriciproducens, Blautia and Lachnospiraceae. The intestinal morphology data showed supplementation with the FSCLP at 80 ppm resulted in a significantly higher (p < 0.05) villus height of the jejunum. This study emphasises the potential of FSCLP as a feasible solution to the issues faced by AMR in chicken production, providing insights into its beneficial impacts on performance, microbial composition, and intestinal health., Competing Interests: DISCLOSURES At the time of research, SC, MP, TA RM, and KH were employed by Alltech. Alltech manufactures and markets animal feed supplements. The authors declare no other conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with heart failure and iron deficiency have diverse causes for hospitalization and death that might be affected by iron repletion., Objectives: The purpose of this study was to explore causes of hospitalizations and deaths in a randomized trial (IRONMAN) of heart failure comparing intravenous ferric derisomaltose (FDI) (n = 568) and usual care (n = 569)., Methods: Patients with heart failure, left ventricular ejection fraction ≤45%, and either transferrin saturation <20% or serum ferritin <100 μg/L were enrolled. Median follow-up was 2.7 years (Q1-Q3: 1.8-3.6 years). A committee adjudicated the main and contributory causes of unplanned hospitalizations and deaths. RRs (rate ratios) for selected recurrent events with 95% CIs are also reported., Results: Compared with usual care, patients randomized to FDI had fewer unplanned hospitalizations (RR: 0.83; 95% CI: 0.71-0.97; P = 0.02), with similar reductions in cardiovascular (RR: 0.83; 95% CI: 0.69-1.01) and noncardiovascular (RR: 0.83; 95% CI: 0.67-1.03) hospitalizations, as well as hospitalizations for heart failure (RR: 0.78; 95% CI: 0.60-1.00), respiratory disease (RR: 0.70; 95% CI: 0.53-0.97), or infection (RR: 0.82; 95% CI: 0.66-1.03). Heart failure was the main cause for 26% of hospitalizations and contributed to or complicated a further 12%. Infection caused or contributed to 38% of all hospitalizations, including 27% of heart failure hospitalizations. Patterns of cardiovascular and all-cause mortality were similar for patients assigned to FDI or usual care., Conclusions: In IRONMAN, FDI exerted similar reductions in cardiovascular and noncardiovascular hospitalizations, suggesting that correcting iron deficiency might increase resistance or resilience to a broad range of problems that cause hospitalizations in patients with heart failure. (Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency; NCT02642562)., Competing Interests: Funding Support and Author Disclosures The IRONMAN trial was funded by the British Heart Foundation (grant CS/15/1/31175). Pharmacosmos supplied FDI and gave additional financial support. Dr Cleland has received funding paid to University of Glasgow for other clinical trials and registries from Bristol Myers Squibb and CSL-Vifor; has received consulting fees paid to University of Glasgow from Pharmacosmos, CSL-Vifor, and Biopeutics; has received honoraria for lectures and support for attending meetings paid to University of Glasgow from Pharmacosmos; is chairperson for data monitoring committees for ADAPT-CRT, CMR-Guide, and PROTECT-HF; and has shares or stock options in HeartFelt (noninvasive monitoring) and Viscardia (synchronous diaphragmatic pacing). Dr Pellicori has received consulting fees from Pharmacosmos, Vifor, and Caption Health; has received honoraria for lectures from AstraZeneca; and has received support for attending meetings from Pharmacosmos. Dr Graham has received personal consulting fees from Vifor; and has received personal support for attending meetings from Pharmacosmos. Dr Petrie has received grants/contracts from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos; has received consulting fees from Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, Abbvie, Bayer, Horizon Therapeutics, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, and 3R Lifesciences; and has participated on data safety monitoring boards for Moderna and Teikoku. Dr Ahmed has received honoraria for lectures from Pharmacosmos. Dr Squire has received grants/contracts from the British Heart Foundation. Dr Ludman has received honoraria for lectures from AstraZeneca; and is chairperson for the British Cardiovascular Society Guidelines and Practice Committee. Dr Japp has received personal consulting fees from Pharmacosmos; has received honoraria for educational events from Novartis and AstraZeneca; has received support for attending meetings from Novartis; has participated on an advisory board for Pharmacosmos; and is Clinical Lead and Chair for Heart Failure Hub Scotland. Dr Al-Mohammad has received personal honoraria for lectures from AstraZeneca, Janssen, Takeda, and Pharmacosmos; has participated on advisory boards for Novartis, Pharmacosmos, AstraZeneca, Boehringer Ingelheim, and Lilly; is a safety monitoring board member for the REACH-HFpEF Study and a UK-HFpEF registry Executive Steering Committee member; and has received equipment from AstraZeneca. Dr Clark is Chair of the Programme Committee for BCS. Dr Szwejkowski has received support for attending meetings from AstraZeneca. Dr McMurray has received personal consulting fees from Alynylam Pharmaceuticals, Bayer, BMS, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, and River 2 Renal Corp; is a director of Global Clinical Trial Partners; has received personal honoraria for lectures from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd., Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals & Pharmaceuticals, Lupin Pharmaceuticals, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, and Translational Medicine Academy; has participated on a data safety monitoring board for George Clinical PTY; and has received funding paid to University of Glasgow for involvement with the following companies/trials: AstraZeneca (DAPA-HF, DELIVER, DETERMINE, DAPA-Resist, DAPA-CKD), Amgen (ATOMIC-HF, COSMIC-HF, GALACTIC-HF), Bayer (FINEARTS), Cardurion (company advisory board), Cytokinetics (GALACTIC-HF), GlaxoSmithKline (ASCEND-D, ASCEND-ND), KBP Biosciences (scientific advisor), and Novartis (PARAGON-HF, PARADISE-MI, PERSPECTIVE, PARACHUTE-HF). Drs Thomson and Robertson have received grants paid to University of Glasgow from the British Heart Foundation and Pharmacosmos. Dr Ford has received grants paid to University of Glasgow from the British Heart Foundation and Pharmacosmos and study drug from Pharmacosmos. Dr Philip Kalra has received funding from Pharmacosmos; has received grants from CSL Vifor, Astellas, Evotec, Pharmacosmos, and Unicyte; has received consulting fees from AstraZeneca, CSL Vifor, Unicyte, and UCB; has received honoraria for lectures from CSL Vifor, AstraZeneca, Pfizer, Pharmacosmos, Napp, and Bayer; and has received support for attending meetings from Pharmacosmos and CSL Vifor. Dr Paul Kalra has received grants paid to University of Glasgow from the British Heart Foundation and Pharmacosmos and to Portsmouth Hospitals University NHS Trust from Pharmacosmos; has received personal consulting fees from Amgen, Boehringer Ingelheim, Pharmacosmos, Servier, and CSL Vifor; has received personal honoraria for lectures from AstraZeneca, Bayer, Novartis, Pfizer, Pharmacosmos, CSL Vifor, and Amgen; has received support for attending meetings from Pharmacosmos; has participated on data safety monitoring boards for the STOP-ACE and EMPRESS-MI trials; and has been Chair-Elect, Chair, and Past Chair for the British Society for Heart Failure. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Evidence is lacking that correcting iron deficiency (ID) has clinically important benefits for patients with heart failure with preserved ejection fraction (HFpEF)., Methods: FAIR-HFpEF was a multicentre, randomized, double-blind trial designed to compare intravenous ferric carboxymaltose (FCM) with placebo (saline) in 200 patients with symptomatic HFpEF and ID (serum ferritin < 100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation < 20%). The primary endpoint was change in 6-min walking test distance (6MWTD) from baseline to week 24. Secondary endpoints included changes in New York Heart Association class, patient global assessment, and health-related quality of life (QoL)., Results: The trial was stopped because of slow recruitment after 39 patients had been included (median age 80 years, 62% women). The change in 6MWTD from baseline to week 24 was greater for those assigned to FCM compared to placebo [least square mean difference 49 m, 95% confidence interval (CI) 5-93; P = .029]. Changes in secondary endpoints were not significantly different between groups. The total number of adverse events (76 vs. 114) and serious adverse events (5 vs. 19; rate ratio 0.27, 95% CI 0.07-0.96; P = .043) was lower with FCM than placebo., Conclusions: In patients with HFpEF and markers of ID, intravenous FCM improved 6MWTD and was associated with fewer serious adverse events. However, the trial lacked sufficient power to identify or refute effects on symptoms or QoL. The potential benefits of intravenous iron in HFpEF with ID should be investigated further in a larger cohort., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: After a young female patient received an intravenous iron infusion for severe symptomatic iron-deficiency-anemia, a severe hypophosphatemia was diagnosed with associated mild muscle weakness. With renal phosphate loss and elevated serum FGF23 (Fibroblast Growth Factor 23), the diagnosis of a hypophosphatemia caused by ferric carboxymaltose was made. Upregulation of FGF23 inhibits renal phosphate reabsorption and also the activation of vitamin D, which additionally reduces intestinal phosphate absorption. The symptoms of hypophosphatemia may be masked after iron replacement., Competing Interests: Die Autorinnen haben keine Interessenkonflikte im Zusammenhang mit diesem Artikel deklariert., (© 2024 Aerzteverlag medinfo AG.)

Objective: To evaluate and compare the blood transfusion requirements during delivery in third-trimester pregnant women with iron deficiency anaemia (IDA) who were treated with intravenous (IV) ferric carboxymaltose (FCM) versus those treated with oral iron supplementation., Study Design: Comparative study. Place and Duration of the Study: Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkiye, from January 2017 to December 2022., Methodology: Pregnant women with haemoglobin (Hb) levels <10 g/dL in their third trimester were included. One group (n = 50) received IV FCM, while the other group (n = 96) received oral iron therapy. Key outcome measures included Hb levels at delivery and the need for a postpartum blood transfusion. Inclusion criteria were third-trimester pregnancy with IDA, and exclusion criteria included haematological or chronic systemic diseases and high-risk pregnancies., Results: The mean initial Hb levels in the third trimester of pregnancy in the FCM group and oral iron group were 8.31 ± 0.96 g/dL and 9.29 ± 1.20 g/dL, respectively (p <0.001). The mean Hb levels in the delivery room were 11.09 ± 1.38 and 9.44 ± 1.16 g/dL, respectively (p <0.001). The rates of postpartum erythrocyte transfusion requirement were 6% (n = 3) and 18.75% (n = 18), respectively (p = 0.037)., Conclusion: IV FCM administration to pregnant patients with IDA during the third trimester was found to be more effective than oral iron treatment in reducing blood transfusion rates., Key Words: Anaemia, Ferric carboxymaltose, Pregnancy, Iron deficiency, Intravenous iron.

Background: Treatment of end stage renal disease (ESRD) is based on preserving renal functions. Since renal anemia is frequently detected, we use parenteral iron treatments in patients with chronic kidney disease (CKD). However, there need to be more precise and sufficient studies on the effect of these treatments on the rate of decrease in the glomerular filtration rate (GFR). Therefore, we conducted a study comparing the rates of change in renal function in patients who had used parenteral iron for at least five years., Methods: Our study is a retrospective cohort study, and 180 patients with CKD (86 women, 94 men, mean age: 63.5 ± 11.4 years) who had been followed and treated in nephrology outpatient clinics for at least five years and met the study criteria were included in the study. Patients were divided into three groups for iron therapy: not receiving iron therapy, iron carboxy maltose (ICM), and iron sucrose (IS) parenterally. Each group consisted of 60 people. The first and last creatinine and GFR values were compared for a 5-year follow-up in each group., Results: There was no significant difference between the two groups, those using and those not using iron, regarding creatinine increase and GFR decrease rate. Additionally, no significant difference was detected in the GFR decline rates of patients using ICM and IS., Conclusions: This study reduces the concerns that correcting anemia through parenteral iron therapy in patients with CKD may harm renal function.

Background: Oral iron for anaemia in pregnancy is often not well tolerated, with poor adherence. Iron administered intravenously might address these tolerance and adherence issues. We investigated the effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate on anaemia and iron deficiency among pregnant women in Nigeria., Methods: We did a multicentre, open-label, parallel, randomised controlled trial of pregnant women (aged 15-49 years) with haemoglobin (Hb) concentrations of less than 10 g/dL at 20-32 weeks' gestation from 11 primary, secondary, or tertiary health facilities in Nigeria (five in Lagos and six in Kano). Exclusion criteria included vaginal bleeding, blood transfusion or major surgery within the past 3 months, symptomatic anaemia, anaemia known to be unrelated to iron deficiency, clinically confirmed malabsorption syndrome, previous hypersensitivity to any form of iron, pre-existing maternal depression or other major psychiatric illness, immune-related diseases, such as systemic lupus erythematosus or rheumatoid arthritis, or severe allergic reactions. Participants were randomly assigned (1:1) by nurses and doctors using a web-based randomisation service to either receive a single dose of intravenous ferric carboxymaltose (20 mg/kg to a maximum of 1000 mg) or oral ferrous sulphate (200 mg; 65 mg elemental iron) three times daily until 6 weeks postpartum. The study was primarily unmasked. Primary outcomes were maternal anaemia (Hb <11 g/dL) at 36 weeks' gestation and preterm birth at before 37 weeks' gestation, with analysis by intention to treat in participants with available data. This study was registered at the ISRCTN registry on Dec 10, 2020 (ISRCTN63484804) and on ClinicalTrials.gov (NCT04976179) on April 7, 2021., Findings: Between Aug 10, 2021, and Dec 15, 2022, 13 724 pregnant women were screened for eligibility. 12 668 were excluded due to ineligibility for inclusion, and 1056 provided consent to participate and were randomly assigned to either the intravenous or oral administration groups. 527 were assigned to the intravenous ferric carboxymaltose group and 529 were assigned to the oral ferrous sulphate group. 518 in the intravenous group were assessed at 36 weeks' gestational age and after 518 deliveries, and 511 completed the 6 weeks postpartum visit. 513 in the oral ferrous sulphate group were assessed at 36 weeks' gestational age and after 512 deliveries, and 501 completed the 6 weeks postpartum visit. No significant difference was found in anaemia at 36 weeks (299 [58%] of 517 in the intravenous group vs 305 [61%] of 503 in the oral group; risk ratio 0·95, 95% CI 0·85-1·06; p=0·36), nor in preterm birth (73 [14%] of 518 vs 77 [15%] of 513; 0·94, 0·70-1·26; p=0·66). There were no significant differences in adverse events. The most common adverse events were diarrhoea (in six participants) and vomiting (in three participants) in the oral group and fatigue (in two participants) and headache (in two participants) in the intravenous group., Interpretation: Although the effect on overall anaemia did not differ, intravenous iron reduced the prevalence of iron deficiency to a greater extent than oral iron and was considered to be safe. We recommend that intravenous iron be considered for anaemic pregnant women in Nigeria and similar settings., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests KSA reports participation on the ALERT project Data Safety Monitoring Board. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aims to investigate sex differences in response to iron supplementation in children and adolescents suffering from sleep-related movement disorders such as Restless Legs Syndrome (RLS), Periodic Limb Movement Disorder (PLMD), and Restless Sleep Disorder (RSD)., Methods: Data were retrieved and reanalyzed from previous studies involving children with RLS, PLMD, or RSD. The analysis included 54 patients treated with intravenous (IV) ferric carboxymaltose (FCM) and 31 patients treated with oral ferrous sulfate (FS). Demographic, biological, and clinical parameters were compared between sexes. Clinical outcomes were measured using the Clinical Global Impression rating scales for severity (CGI-S) and improvement (CGI-I)., Results: In the group treated with IV FCM, no significant differences were found between males and females in demographic (age), biological (ferritin, iron, total iron-binding capacity, transferrin), or clinical parameters (CGI-S and CGI-I). However, among adolescents, females showed significantly better clinical improvement (CGI-I) compared to males (t-value 2.428, p < 0.024). In the group treated with oral FS, no significant sex differences were observed in any parameters. Side effects were reported by a small number of patients, with no significant difference between sexes., Conclusion: The findings indicate no major significant sex-based differences in response to iron supplementation for treating sleep-related movement disorders in children and adolescents, despite distinct hormonal and physiological differences in iron metabolism. Both boys and girls benefit similarly from iron treatment during this developmental stage, suggesting that a standardized approach to iron supplementation may be effective. However, individual assessment and monitoring remain crucial to ensure optimal outcomes., Competing Interests: Declaration of competing interest The authors do not have any financial or personal relationships with other people or organizations that could inappropriately influence (bias) this work. Artificial intelligence was not used in the writing of this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Limited evidence exists on the optimal strategy to correct iron deficiency anemia after variceal bleeding (VB) in cirrhosis. This trial compared the efficacy and safety of intravenous ferric carboxymaltose (IV-FCM) with those of oral iron therapy in this cohort., Methods: In this open-label, single-center, randomized controlled trial, eligible patients with hemoglobin <10 g/dL and iron deficiency (ferritin <100 ng/mL) after VB received either IV-FCM (1,500-2,000 mg) divided into 2 doses (n = 48) or oral carbonyl iron (100 mg elemental iron/day) (n = 44) for 3 months. The primary outcome was change in hemoglobin at 3 months. Secondary outcomes included improvement in anemia (last hemoglobin >12 g/dL), normalization of iron stores (ferritin >100 ng/mL), liver-related adverse events, adverse drug reactions, and changes in quality of life (CLDQOL questionnaire)., Results: Baseline characteristics, including median Child-Turcotte-Pugh score 7 (interquartile range [IQR] 6-9), Model for End-Stage Liver Disease score 12 (IQR 10-17), blood hemoglobin (8.25 ± 1.06 g/dL), and ferritin (30.00 ng/mL [15.00-66.50]), were comparable in both arms. The median increase in hemoglobin at 3 months in the IV and oral arms was 3.65 g/dL (IQR 2.55-5.25) and 1.10 g/dL (IQR 0.05-2.90 g/dL) ( P < 0.001), respectively. Iron stores normalized in 84.6% and 21% of the IV and oral arms, respectively ( P < 0.001). Anemia improved in 50% and 21.9% in the IV and oral arms, respectively ( P < 0.009). Patients in the IV arm showed a significant improvement in all domains of CLDQOL. Liver-related adverse events were comparable in both arms. Transient mild/moderate hypophosphatemia developed in 43% of patients receiving IV-FCM., Discussion: Intravenous iron replacement is efficacious and safe to treat iron deficiency anemia after VB in patients with cirrhosis., (Copyright © 2024 by The American College of Gastroenterology.)

Background: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part Phase 2 study evaluated the tolerability, safety and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD)., Methods: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50 and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50 or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus., Results: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during Weeks 1-2 of treatment). Most gastrointestinal disorders resolved without intervention, and none was serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day [mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2) and -1.4 (-2.2, -0.5) mg/dL, respectively]. In both parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation., Conclusion: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD., Clinical Trial Registration Number: NCT04551300 ., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Introduction: Up to 24.2% Malaysians are estimated to be affected by anaemia. Iron deficiency is the most common nutritional deficiency leading to anaemia. Oral iron therapy may not be well tolerated or efficient. Ferric carboxymaltose (FCM), a non-dextran intravenous iron formulation, may be an appealing alternative for iron replacement therapy. This retrospective study aimed to investigate the efficacy and safety of intravenous FCM infusion for the management of iron deficiency anaemia in a single centre in Malaysia., Materials and Methods: All patients who received at least one dose of 500 mg intravenous FCM infusion from January to December 2023 in Bukit Tinggi Medical Centre (BTMC) were identified from the electronic medical record database. Inclusion criteria were patients: (1) ≥ 14 years old and (2) with iron deficiency anaemia. The primary outcome was the mean change in haemoglobin level before treatment and 30 day after treatment. Secondary outcomes included reasons for intravenous FCM infusion, median dose, adverse drug reactions, mean change in haemoglobin levels for different subgroups and percentage of patients with normalised haemoglobin after treatment. The efficacy outcome was analysed using per-protocol analysis while the safety outcome used intention-to-treat analysis. Paired t-test was used to compare the mean difference between the haemoglobin measurements before and 30-day after treatment., Results: A total of 144 administrations were given to 141 patients requiring intravenous iron replacement therapy during the 1-year study period in BTMC. Intravenous FCM infusion was administered for the management of iron deficiency related to: (1) increased blood loss, including menorrhagia, haemorrhoids and GI-related surgery, (2) low iron intake, including poor nutrition and gastrointestinalrelated malabsorption and (3) haematological disorders, including autoimmune haemolytic anaemia, myelodysplastic syndrome, diffuse large B-cell lymphoma and idiopathic thrombocytopaenia purpura. The median dose of intravenous FCM infusion was 1000 mg. At 30 day post-infusion, the mean haemoglobin level increased significantly from 8.9 g/L to 11.6 g/L (p < 0.05), an increase of 2.68 g/L (95% CI: 2.45 - 2.90 g/L). No adverse drug reactions were reported. Subgroup analysis showed that patients with haematological disorders had significantly higher improvement in haemoglobin levels after intravenous iron infusion compared to those without. At 7-day, 14-day, 21-day post-infusion, 33% (33/99), 34% (34/99) and 36% (36/99) patients had a normalised haemoglobin level, respectively. The proportion of patients with a normalised haemoglobin level increased to 36% (36/99) and 42% (42/99) at 30-day and 90-day post-infusion., Conclusion: Within the limit of this single-centre retrospective study, intravenous FCM infusion was well tolerated and effective in increasing the haemoglobin level among patients with iron deficiency anaemia.

Although it has been established that patients with chronic kidney disease and iron deficiency, as indicated by a transferrin saturation of < 20%, are at increased risk of all-cause mortality and cardiovascular events, the optimal management of such patients has not yet been determined. In this post hoc subgroup analysis, we aimed to clarify the effect of ferric citrate hydrate on transferrin saturation in patients with chronic kidney disease and low transferrin saturation (< 20%) undergoing hemodialysis. To accomplish this, we extracted the relevant data on a subset of patients drawn from two previous studies: the ASTRIO study (A Study examining the contribution to Renal anemia treatment with ferric citrate hydrate, Iron-based Oral phosphate binder, UMIN000019176) and a post-marketing surveillance study. The subset of patients used for the present study were those with baseline transferrin saturation < 20%. We found that administration of ferric citrate hydrate increased transferrin saturation and maintained transferrin saturation at approximately 30%. However, because we did not have access to data on all-cause mortality or cardiovascular events, we could not ascertain whether the frequency of these outcomes was reduced in parallel with improvements in transferrin saturation. Further large studies are required.

Introduction: Postpartum anaemia is often caused by iron deficiency with onset during the antepartum period and can be exacerbated by excessive blood loss at birth. Its prevalence is estimated as 50-80% in low-income and middle-income countries. It poses adverse consequences on the mother and negatively impacts her ability to care for her newborn. Prompt treatment of postpartum anaemia is thus important. Adherence to oral iron is reportedly low in Nigeria due to its side effects and forgetfulness by the mothers. Intravenous iron such as ferric carboxymaltose, given as a single dose, might help overcome adherence issues, but investigation in a high-quality randomised control trial in Nigeria is first required while evaluation of challenges around its implementation is also warranted., Objective: To determine the clinical effectiveness, tolerability and safety, of using intravenous ferric carboxymaltose (intervention) vs oral ferrous sulphate (control) for treating moderate to severe iron deficiency anaemia in postpartum women and to evaluate implementation of ferric carboxymaltose in treating postpartum anaemia in Nigeria., Methods and Analysis: This study is an open-label randomised controlled trial with a concurrent implementation study. It is a hybrid type 1 effectiveness-implementation design conducted in four states across Northern and Southern Nigeria. A total of 1400 eligible and consenting women with postpartum moderate to severe anaemia (haemoglobin concentration <100 g/L) will be randomised to intravenous ferric carboxymaltose; a single dose at 20 mg/kg to a maximum of 1000 mg infusion administered at enrolment (intervention) or oral ferrous sulphate; 200 mg (65 mg elemental iron) two times per day from enrolment until 6 weeks postpartum (control). The primary outcome, proportion of participants who are anaemic (Hb <110 g/L) at 6 weeks postpartum will be analysed by intention-to-treat. Haemoglobin concentration, full blood count, serum iron, serum ferritin, transferrin saturation and total iron binding capacity will be measured at specific intervals. Implementation outcomes such as acceptability and feasibility of using ferric carboxymaltose for postpartum anaemia treatment in Nigeria will be assessed., Ethics and Dissemination: This study is approved by the ethics committee of the teaching hospitals, Ministry of Health of the four states as required, National Health Research Ethics Committee and the drug regulatory agency, National Agency for Food and Drug Administration and Control (NAFDAC). Findings of this research will be presented at conferences and will be published in international peer-reviewed journals and shared with stakeholders within and outside Nigeria., Trial Registration Number: International standard randomised controlled trial number: ISRCTN51426226., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

This article highlights a case of high-dose ferric carboxymaltose (Ferinject ® ) for the treatment of perioperative iron deficiency anaemia in a 39-year-old patient with dysplastic coxarthrosis. The patient was admitted routinely for a total hip replacement of the left hip joint. She had been suffering from pain, lameness, and restriction of movement in her left hip joint for the past several years. The patient was admitted with initial iron deficiency anaemia of a medium severity (Hgb-96.5 g/L, RBC-3.97 × 10 12 /L). Laboratory tests were taken to determine the iron deficiency, and transfusion readiness was submitted. The patient received ferric carboxymaltose infusion before surgery. The intraoperative blood loss was-100 mL with an operation duration of 50 min. On the first postoperative day, haemoglobin decreased to 86 g/L. No haemoglobin decrease was observed in the postoperative period, and 92 g/L was the amount of haemoglobin at the time of hospital discharge. The optimal dose for the treatment of perioperative anaemia has not been established; some studies recommend ferric carboxymaltose at a dose of 15 to 20 mg/kg and a maximum of 1000 mg once on the first day after surgery. The uniqueness of this case report is that a high dose of ferric carboxymaltose (1340 mg) during the preoperative period was applied. No side effects such as hypophosphatemia were reported. We believe that, in this clinical case, the patient managed to avoid large intraoperative blood loss and transfusions by using high doses of ferric carboxymaltose.

Background: Iron deficiency (ID) is common in patients with pulmonary arterial hypertension and has been associated with increased morbidity and mortality. We aimed to evaluate the therapeutic effects of iron supplementation in iron deficient patients with group 1 to 4 pulmonary hypertension (PH). Methods: A total of 85 PH patients (mean age 69.8 ± 12.0 years, 56.5% female) were included in this prospective trial. Patients were screened for ID at baseline. PH patients with ID received intravenous iron supplementation (500-1000 mg ferric carboxymaltose). PH patients without ID served as control group. At baseline and 16-week follow up, six-minute walk test (6MWT), laboratory testing and echocardiography were performed. Additionally, World Health Organization (WHO) functional class, fatigue score and quality of life (QoL) by the SF-36 questionnaire were assessed. Results: Overall, ID was present in 26.7% (n=8/30), 37.5% (n=9/24), 45.5% (n=10/22) and 44.4% (n=4/9) of patients in PH groups 1-4, respectively. In the total study population, iron restoration led to a significant mitigation of fatigue (p=0.01). However, 6MWT, WHO function class, NT-proBNP levels, QoL and right ventricular function did not change significantly. With regard to the underlying PH group, only PH group 3 patients experienced significant improvements in 6MWT distance (p=0.019), WHO functional class (p=0.017), fatigue (p=0.009) and some QoL domains, as compared to controls. Conclusions: ID was common in PH groups 1 to 4. Though intravenous iron supplementation adequately restored iron status and improved fatigue throughout all patients, in the underlying PH groups treatment was accompanied by improvements in exercise capacity, WHO function class and fatigue only in group 3 PH., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Iron deficiency anemia is one of the most common types of anemia, but real-world clinical management practices in Japan are unclear. This study retrospectively explored iron prescription patterns, treatment effectiveness, and assessments. Patients with at least one treatment period between September 2020 and September 2022 were included and classified into three groups (ferric carboxymaltose [FCM]: 7437 patients, saccharated ferric oxide [SFO]: 98,648 patients, and oral iron: 359,547 patients). Iron-related laboratory values over time and testing proportions were evaluated. Median baseline hemoglobin levels were lowest with FCM (FCM: 8.10 g/dL, SFO: 8.70 g/dL, oral iron: 9.70 g/dL), but changes in hemoglobin levels by 12 weeks were greatest with FCM (FCM: 3.20 g/dL, SFO: 2.60 g/dL, oral iron: 1.70 g/dL). The median serum ferritin level at 8 weeks after FCM treatment was 43.70 ng/mL for ≤500 mg, versus 123.30 ng/mL for >500 to ≤1500 mg. All groups had a low proportion of serum ferritin and transferrin saturation (TSAT) testing at diagnosis (<38%), which decreased further for post-treatment assessment (<24%). This study suggests the importance of prescribing an appropriate total iron cumulative dose per the package insert, along with diagnosis and assessments based on serum ferritin/TSAT., (© 2024. The Author(s).)

Purpose: Iron deficiency anemia is common in people with inflammatory bowel disease (IBD), causing deterioration in quality of life, which can be reversed by treatment that increases iron stores and hemoglobin levels. The present post hoc analyses estimate health state utility values for patients with IBD after treatment with ferric derisomaltose or ferric carboxymaltose and evaluate the health domains driving the changes., Methods: SF-36v2 responses were recorded at baseline and day 14, 35, 49, and 70 from 97 patients enrolled in the randomized, double-blind, PHOSPHARE-IBD trial (ClinicalTrials.gov ID: NCT03466983), in which patients with IBD across five European countries were randomly allocated to either ferric derisomaltose or ferric carboxymaltose. Changes in SF-36v2 scale scores and SF-6Dv2 health utility values were analyzed by mixed models., Results: In both treatment arms, SF-6Dv2 utility values and all SF-36v2 scale scores, except Bodily Pain, improved significantly (p =  < 0.0001). The improvement in SF-6Dv2 utility values showed no significant treatment group difference. The improvement in utility values was completely explained by improvement in Vitality scores. Vitality scores showed significantly larger improvement with ferric derisomaltose versus ferric carboxymaltose (p = 0.026). Patients with the smallest decrease in phosphate had significantly larger improvements in Vitality scores at each time point (p =  < 0.05 for all comparisons) and overall (p = 0.0006)., Conclusions: Utility values improved significantly with intravenous iron treatment. Improvement in utility values was primarily driven by Vitality scores, which showed significantly greater improvement in the ferric derisomaltose arm. Smaller decreases in phosphate were associated with significantly higher Vitality scores, suggesting that quality of life improvement is attenuated by hypophosphatemia. The utility values can inform future cost-utility analysis., (© 2024. The Author(s).)

Aims: Bariatric surgery induces several micronutrient deficiencies that require supplementation. For iron, parenteral infusions are usually preferred over oral supplementation. Ferric carboxymaltose infusion has been associated with hypophosphataemia, mostly transient and asymptomatic. However, in some cases, ferric carboxymaltose-induced hypophosphataemia may persist for weeks to months and may induce muscle weakness, osteomalacia and bone fractures. The aim of this study was to identify possible predictors of a clinically relevant decrease in serum phosphate after ferric carboxymaltose infusion in patients with previous Roux-en-Y gastric bypass., Methods: Patients with previous Roux-en-Y gastric bypass who received ferric carboxymaltose infusions between January 2018 and September 2019 and had recorded phosphataemia before and after ferric carboxymaltose infusion at the Lausanne University Hospital, Lausanne, Switzerland, were studied retrospectively. A multiple linear regression model was built with delta phosphataemia as the outcome to investigate the factors related to magnitude of serum phosphate lowering., Results: Seventy-seven patients (70 females and 7 males) with previous Roux-en-Y gastric bypass were studied. Mean age (SD) was 43.2 (10.7) years and median BMI was 30.9 kg/m2 (IQR 27.9-36.4). Sixty-eight patients (88.3%) received an infusion of 500 mg ferric carboxymaltose and 9 patients (11.7%) received 250 mg ferric carboxymaltose. Forty-nine patients (63.6%) developed hypophosphataemia (<0.8 mmol/l) after ferric carboxymaltose infusion. Median plasma phosphate significantly decreased by 0.33 mmol/l (IQR 0.14-0.49) (p<0.0001). Multiple linear regression identified the ferric carboxymaltose dose as the only risk factor significantly associated with the magnitude of serum phosphate lowering, with an additional mean loss of 0.26 mmol/l with a 500 mg infusion compared to a 250 mg infusion (p = 0.020)., Conclusion: Ferric carboxymaltose infusions substantially decreased plasma phosphate levels in patients with previous Roux-en-Y gastric bypass. Compared to a dose of 250 mg, infusion of a dose of 500 mg ferric carboxymaltose decreased the plasma phosphate further in this population.

Objective: This study aimed to assess the efficacy of different oral iron preparations prescribed for prevention of iron deficiency anemia in healthy infants., Methods: This retrospective study enrolled infants aged between 6 and 12 months who were initiated on iron prophylaxis at four months of age. Enrolled children consistently used specific iron preparations (ferrous, ferric or liposomal iron) and had their complete blood counts and serum ferritin levels assessed within the 6-12 month timeframe. Blood values and iron prophylaxis type (ferrous (Fe+2), ferric (Fe+3), liposomal iron) were recorded. Chi-square test was used to compare the hemoglobin and ferritin levels levels between groups. Univariate and multivariate regression analyses assessed the risk of anemia., Results: The study included 371 children (ferrous sulphate - 60, iron hydroxide-polymaltose complex - 137 and liposomal ferric pyrophosphate - 174) with a mean (SD) age 9.1 (1.3) mo. Iron deficiency in different groups were: liposomal iron (46.0%), ferric iron (44.5%), and ferrous iron (5.0%). Mean (SD) serum ferritin levels (µg/L) were higher in the ferrous group [30.1 (10.8)] compared to infants receiving ferric [17.6 (14.50)] and liposomal iron [15.4 (12.1)] (P < 0.001). Mean (SD) hemoglobin levels (g/dL) were significantly higher in the ferrous group [12.4 (0.8)] compared to ferric [11.9 (1.1)] and liposomal iron group [12.0 (1.1)]; P =0.008. Multiple regression analysis showed that ferrous group was associated with a lower risk of iron deficiency [OR (95% CI) 0.04 (0.01-0.15), P < 0.001]., Conclusion: Ferrous iron demonstrated superior efficacy compared to ferric and liposomal iron. Further studies are needed to establish alternative iron preprations in children.

Study Objectives: Iron therapy is associated with improvements in restless legs syndrome (RLS). This multicenter, randomized, double-blind study evaluated the effect of intravenous ferric carboxymaltose (FCM) on RLS., Methods: A total of 209 adult patients with a baseline International RLS (IRLS) score ≥ 15 were randomized (1:1) to FCM (750 mg/15 mL) or placebo on study days 0 and 5. Ongoing RLS medication was tapered starting on Day 5, with the goal of discontinuing treatment or achieving the lowest effective dose. Co-primary efficacy endpoints were changed from baseline in IRLS total score and the proportion of patients rated as much/very much improved on the Clinical Global Impression (CGI)-investigator (CGI-I) scale at day 42 in the "As-Treated" population., Results: The "As-Treated" population comprised 107 FCM and 101 placebo recipients; 88 (82.2%) and 68 (67.3%), respectively, completed the day 42 assessment. The IRLS score reduction was significantly greater with FCM versus placebo: least-squares mean (95% confidence interval [CI]) -8.0 (-9.5, -6.4) versus -4.8 (-6.4, -3.1); p = .0036. No significant difference was observed in the proportion of FCM (35.5%) and placebo (28.7%) recipients with a CGI-I response (odds ratio 1.37 [95% CI: 0.76, 2.47]; p = .2987). Fewer patients treated with FCM (32.7%) than placebo (59.4%) received RLS interventions between day 5 and study end (p = .0002). FCM was well tolerated., Conclusions: The IRLS score improved with intravenous FCM versus placebo, although the combination of both co-primary endpoints was not met. Potential methodological problems in the study design are discussed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Hypophosphatemia may cause serious complications. Depending on its severity and duration, signs and symptoms range from fatigue to life-threatening events, like severe rhabdomyolysis and mental status changes. Long-term consequences include osteomalacia. Hypophosphatemia may be secondary to the use of parental iron, mostly associated with ferric carboxymaltose (FCM), with an incidence of around 45% to 70%. We describe three cases of hypophosphatemia in patients with chronic iron deficiency anemia, requiring repeated FCM infusions. The patients' presentation to the Rheumatology department included musculoskeletal symptoms of severe hypophosphatemia and long-term hypophosphatemic osteomalacia, with fractures. We aim to raise awareness for ferric carboxymaltose-induced hypophosphatemia, an entity increasingly described in the literature that can be responsible for severe disability or potentially life-threatening adverse events.

Background: Iron deficiency anemia (IDA) increases levels of C-terminal fibroblast growth factor 23 (cFGF23) and platelet count (PLT), each of which is associated with cardiovascular events. Therefore, we hypothesized that iron replacement with ferric citrate hydrate (FC) would decrease cFGF23 levels and PLT in patients with IDA., Methods: In a randomized, open-label, multicenter, 24-week clinical trial, patients with non-dialysis-dependent chronic kidney disease (CKD) and non-CKD complicated by IDA (8.0 ≤ hemoglobin < 11.0 g/dL; and serum ferritin < 50 ng/mL [CKD]; < 12 ng/mL [non-CKD]) were randomized 1:1 to FC-low (500 mg: approximately 120 mg elemental iron/day) or FC-high (1000 mg: approximately 240 mg elemental iron/day). If sufficient iron replacement had been achieved after week 8, further treatment was discontinued., Results: Seventy-three patients were allocated to FC-low (CKD n = 21, non-CKD n = 15) and FC-high (CKD n = 21, non-CKD n = 16). Regardless of CKD status, FC increased serum ferritin and transferrin saturation, did not change intact FGF23 or serum phosphorus, but decreased cFGF23. In FC-low group, median changes in cFGF23 from baseline to week 8 were -58.00 RU/mL in CKD and -725.00 RU/mL in non-CKD; in FC-high group, the median changes were -66.00 RU/mL in CKD and -649.50 RU/mL in non-CKD. By week 8, FC treatment normalized PLT in all patients with high PLT at baseline (>35.2 × 10 4 /µL; FC-low: 1 CKD, 8 non-CKD; FC-high: 3 CKD, 8 non-CKD)., Conclusion: Regardless of CKD status, iron replacement with FC decreased elevated cFGF23 levels and normalized elevated PLT in patients with IDA., Clinical Trial Registration Number: jRCT2080223943., (© 2024. The Author(s).)

Collagenous gastritis (CG) is a rare histopathological finding on gastric biopsies in children. It is associated with abdominal pain and iron deficiency anemia, usually not respondent to oral iron supplements. The aim of this study was to describe our experience in the management of pediatric patients with CG. Moreover, we propose to review the literature on this topic. We retrospectively reviewed all pediatric patients diagnosed with CG at our centre from January 2014 to January 2019. Three pediatric patients (2 F, mean age 12.3) were diagnosed with CG during the study period. Two presented with moderate and one with severe anemia. Symptoms were abdominal pain, asthenia and headache in two and asthenia and abdominal pain in one. All underwent upper and lower gastrointestinal endoscopy. All were firstly started with oral iron supplements with no benefit, principally due to poor compliance secondary to the worsening of the epigastric pain and proton pump inhibitor resistance. Therefore, they underwent ferric carboxymaltose (FCM) infusion with good clinical and laboratory response. Patients received a mean of two infusions/year, with stable hemoglobin levels and no adverse outcomes. Our review failed to identify a consistent response to specific treatments. Considering the apparent benign nature of the disease, symptomatic and supportive treatments are advisable. Iron deficiency anemia is largely present and therapy with oral iron supplements is not always successful. In our study, FCM infusion was effective in increasing the key blood indices in patients who poorly tolerated oral supplements., (© 2023. Indian Society of Gastroenterology.)

Background: Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied., Aims: This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB., Methods: This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9-11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180., Results: From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups., Conclusions: Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To investigate the hepatic effects of high-dose intravenous (IV) iron, including those on liver function and the degree of fibrosis, in a rat model of cirrhosis., Methods: We evenly allocated 25 Sprague-Dawley rats into five groups: normal rats (control group), cirrhotic rats receiving IV normal saline (liver cirrhosis [LC] group), and cirrhotic rats receiving 20, 40, or 80 mg/kg IV ferric carboxymaltose (LC-iron20, LC-iron40, and LC-iron80 group, respectively). Biochemical parameters were compared at 0, 7, 14, 21, and 28 days. The degrees of hepatic fibrosis and iron deposition were evaluated. Inflammatory and oxidative stress markers were also compared., Results: There were no significant differences in the 28-day serum alanine aminotransferase levels among the LC-iron20, LC-iron40, and LC-iron80 groups (69 ± 7, 1003 ± 127, 1064 ± 309, 919 ± 346, and 820 ± 195 IU/L in the control, LC, LC-iron20, LC-iron40, and LC-iron80 groups, respectively). Hepatic iron accumulation increased in a dose-dependent manner, but the degree of hepatic fibrosis was comparable among the groups. The inflammatory and oxidative stress marker levels did not differ significantly according to the IV iron dose., Conclusions: Administration of IV iron at various high doses appears safe in our rat model of cirrhosis., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Background: In some countries, intravenous ferric derisomaltose (FDI) is only licensed for treating iron deficiency with anemia. Accordingly, we investigated the effects of intravenous FDI in a subgroup of patients with anemia in the IRONMAN (Effectiveness of Intravenous (IV) Iron Treatment Versus Standard Care in Patients With Heart Failure and Iron Deficiency) trial., Method and Results: IRONMAN enrolled patients with heart failure, a left ventricular ejection fraction of ≤45%, and iron deficiency (ferritin <100 µg/L or transferrin saturation of <20%), 771 (68%) of whom had anemia (hemoglobin <12 g/dL for women and <13 g/dL for men). Patients were randomized, open label, to FDI (n = 397) or usual care (n = 374) and followed for a median of 2.6 years. The primary end point, recurrent hospitalization for heart failure and cardiovascular death, occurred less frequently for those assigned to FDI (rate ratio 0.78, 95% confidence interval 0.61-1.01; P = .063). First event analysis for cardiovascular death or hospitalization for heart failure, less affected by the coronavirus disease 2019 pandemic, gave similar results (hazard ratio 0.77, 95% confidence interval 0.62-0.96; P = .022). Patients randomized to FDI reported a better Minnesota Living with Heart Failure quality of life, for overall (P = .013) and physical domain (P = .00093) scores at 4 months., Conclusions: In patients with iron deficiency anemia and heart failure with reduced left ventricular ejection fraction, intravenous FDI improves quality of life and may decrease cardiovascular events., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron., Data Source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women., Selection of Studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected., Data Collection: Two reviewers independently extracted data from nine selected trials., Data Synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron., Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women., Competing Interests: Conflicts to interest: none to declare., (© 2024. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

Introduction: Ferric citrate (FC) is an FDA-approved iron-based phosphate binder for adults with dialysis-dependent chronic kidney disease. This study investigated the impact of FC as the primary phosphate-lowering therapy on utilization of erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron., Methods: In this randomized, open-label, active-controlled, multicenter study (NCT04922645), patients on dialysis and receiving ESAs were randomized to receive FC or remain on standard of care (SOC) phosphate-lowering therapy for up to 6 months. Primary endpoints were the difference in change from baseline to efficacy evaluation period (EEP) in mean monthly ESA and IV iron doses. Secondary endpoints included treatment differences in hemoglobin, phosphate, TSAT, and ferritin levels., Results: Two hundred nine patients were randomized to FC and had a day 1 dosing visit (n = 103) or SOC (n = 106). The two groups had similar baseline laboratory characteristics; however, atherosclerotic CV disease, peripheral vascular disease, and congestive heart failure were more common in the SOC group. The mean treatment difference in ESA monthly dose was -30.8 μg (FC vs. SOC; p = 0.02). An absolute though non-statistically significant change in mean monthly IV iron dose of -37.2 mg (p = 0.17) was observed with FC. Mean hemoglobin, TSAT, and ferritin all increased from baseline to the EEP with FC versus SOC. Serious adverse events occurred in 28% of patients receiving FC versus 37% in those receiving SOC., Conclusions: In patients receiving dialysis, treatment with FC as compared to remaining on SOC phosphate binders resulted in reductions in mean monthly ESA and IV iron dose., (© 2024 S. Karger AG, Basel.)

Introduction: Iron deficiency is the most common cause of anemia in both sexes, although it is more common in women. Intravenous (IV) iron replacement is preferred in patients who cannot tolerate oral treatment or when iron stores need to be replenished rapidly. In this study, we wanted to share the ferric carboxymaltose (FCM) desensitization protocol that we self-created and successfully applied., Methods: This retrospective cross-sectional study included patients with a history of hypersensitivity reactions (HSRs) to IV or oral iron replacement and patients who were planned to receive IV iron replacement but were referred to the allergy clinic because of have risk factors (atopic diseases, history of HSR to other drugs, high serum tryptase levels, etc.) for HSRs. Before desensitization, some of the patients underwent skin tests (skin prick test and intradermal test) with FCM, and the results were recorded. Skin tests were not performed in patients with a history of drug use (antihistamine, systemic steroid, omalizumab, etc.) that affected the results of skin tests. All patients underwent a one-bag 8-step desensitization protocol with 500 mg FCM and were observed for 2 h after desensitization., Results: A total of 15 patients (14 females and 1 male) with a mean age of 41.13 ± 11.18 years were included in the study. When the patients were evaluated in terms of the risk of allergic reactions according to their clinical history, 8 patients had a history of anaphylaxis with iron preparations (FCM, n = 4; ferric hydroxide sucrose, n = 2; iron [II] glycine sulfate, n = 1; and iron [III] hydroxide polymaltose, n = 1), and 7 patients had a history of HSR other than anaphylaxis with iron preparations (urticaria, n = 6 [FCM, n = 2; iron (II) glycine sulfate, n = 2; and iron (III) hydroxide polymaltose, n = 2] and urticaria + angioedema [ferric hydroxide sucrose, n = 1]). Desensitization was successfully completed in all patients. No HSR was observed during or after the procedure in any of the patients., Conclusion: IV iron replacement is a very effective method, especially in cases where iron stores need to be replenished more rapidly. In patients with a history of iron HSR or at risk of developing HSR, replacement can be safely performed without an allergic reaction with successful desensitization protocols., (© 2024 S. Karger AG, Basel.)

Background: Skeletal muscle dysfunction is a feature of heart failure (HF). Iron deficiency (ID) is prevalent in patients with HF associated with exercise intolerance and poor quality of life. Intravenous iron in iron deficient patients with HF has attenuated HF symptoms, however the pathomechanisms remain unclear. The aim of study was to assess whether intravenous iron supplementation as compared to placebo improves energy metabolism of skeletal muscles in patients with HF., Methods: Men with heart failure with reduced ejection fraction (HFrEF) and ID were randomised in 1:1 ratio to either intravenous ferric carboxymaltose (IV FCM) or placebo. In vivo reduction of lactates by exercising skeletal muscles of forearm was analyzed. A change in lactate production between week 0 and 24 was considered as a primary endpoint of the study., Results: There were two study arms: the placebo and the IV FCM (12 and 11 male patients with HFrEF). At baseline, there were no differences between these two study arms. IV FCM therapy as compared to placebo reduced the exertional production of lactates in exercising skeletal muscles. These effects were accompanied by a significant increase in both serum ferritin and transferrin saturation in the IV FCM arm which was not demonstrated in the placebo arm., Conclusions: Intravenous iron supplementation in iron deficient men with HFrEF improves the functioning of skeletal muscles via an improvement in energy metabolism in exercising skeletal muscles, limiting the contribution of anaerobic reactions generating ATP as reflected by a lower in vivo lactate production in exercising muscles in patients with repleted iron stores.

Background: Gynecological pathologies are an important cause of anemia in women. In this study, we aimed to evaluate women who had been hospitalized because of anemia (Hb level <10 g/dL) caused by gynecologic pathologies and treated with either intravenous iron (ferric carboxymaltose) or blood transfusion., Methods: This retrospective cross-sectional study was performed in a tertiary care center. Women who were hospitalized with the diagnosis of anemia with Hb level<10 g/dL and abnormal uterine bleeding between March 2015- September 2017 in the gynecology clinic were enrolled in the study. Hemoglobin levels, hemoglobin changes, uterine pathology and treatment of patients were recorded and compared., Results: One hundred and fifteen women received red blood cell transfusion and 100 women were treated with intravenous ferric carboxymaltose. The mean age of the women was 45.1±6.1 (22-57) years. Although the mean Hb levels were higher in the iv-iron replacement group at the end of the one month (P=0.001), the mean increase in Hb levels was similar between two treatment modalities (P=0.101). Among the anemic women who required surgery, iv iron replacement was the first choice in 75.9% of women; 34.1% received red blood cell transfusion in the preoperative period., Conclusions: Gynecological pathologies are a common cause of anemia in reproductive age women and intravenous carboxymaltose treatment is a safe and cheaper alternative of blood-transfusion in appropriate cases to elevate the Hb levels in the preoperative period.

Purpose: To compare the efficacy of intravenous (IV) iron (ferric derisomaltose) with oral iron (ferrous fumarate) in women 14-21 weeks pregnant with persistent iron deficiency (ferritin < 30 µg/L)., Methods: In a single-centre, open-label, randomised controlled trial at a Danish hospital, women with persistent iron deficiency after routine oral iron treatment were allocated to receive 1000 mg IV iron (single-dose) or 100 mg elemental oral iron daily. Outcomes were assessed during an 18-week follow-up period. The primary endpoint was the proportion of non-anaemic (haemoglobin [Hb] ≥ 11 g/dL) women throughout follow-up. Other outcomes included changes in haematological parameters, patient-reported fatigue, and quality of life (QoL). Safety was assessed by recording adverse events., Results: From July 2017 to February 2020, 100 women were randomised to IV iron and 101 to oral iron. Throughout follow-up, 91% of women were non-anaemic in the IV iron group compared with 73% in the oral iron group (18% difference [95% confidence interval 0.10-0.25]; p < 0.001). The mean Hb increase was significantly greater with IV iron versus oral iron at Weeks 6 (0.4 versus - 0.2 g/dL; p < 0.001), 12 (0.5 versus 0.1 g/dL; p < 0.001), and 18 (0.8 versus 0.5 g/dL; p = 0.01). Improvements in fatigue and QoL were greater with IV iron versus oral iron at Weeks 3 and 6. The incidence of treatment-related adverse events was comparable between treatment groups., Conclusion: IV iron was superior in preventing anaemia compared with oral iron in pregnant women with persistent iron deficiency; biochemical superiority was accompanied by improved fatigue and QoL., Clinical Trial Registration: European Clinical Trials Database: EudraCT no.: 2017-000776-29 (3 May 2017); ClinicalTrials.gov: NCT03188445 (13 June 2017). The trial protocol has been published: https://dx.doi.org/10.1186%2Fs13063-020-04637-z ., (© 2022. The Author(s).)

Background: Ferric carboxymaltose therapy reduces symptoms and improves quality of life in patients who have heart failure with a reduced ejection fraction and iron deficiency. Additional evidence about the effects of ferric carboxymaltose on clinical events is needed., Methods: In this double-blind, randomized trial, we assigned ambulatory patients with heart failure, a left ventricular ejection fraction of 40% or less, and iron deficiency, in a 1:1 ratio, to receive intravenous ferric carboxymaltose or placebo, in addition to standard therapy for heart failure. Ferric carboxymaltose or placebo was given every 6 months as needed on the basis of iron indexes and hemoglobin levels. The primary outcome was a hierarchical composite of death within 12 months after randomization, hospitalizations for heart failure within 12 months after randomization, or change from baseline to 6 months in the 6-minute walk distance. The significance level was set at 0.01., Results: We enrolled 3065 patients, of whom 1532 were randomly assigned to the ferric carboxymaltose group and 1533 to the placebo group. Death by month 12 occurred in 131 patients (8.6%) in the ferric carboxymaltose group and 158 (10.3%) in the placebo group; a total of 297 and 332 hospitalizations for heart failure, respectively, occurred by month 12; and the mean (±SD) change from baseline to 6 months in the 6-minute walk distance was 8±60 and 4±59 m, respectively (Wilcoxon-Mann-Whitney P = 0.02; unmatched win ratio, 1.10; 99% confidence interval, 0.99 to 1.23). Repeated dosing of ferric carboxymaltose appeared to be safe with an acceptable adverse-event profile in the majority of patients. The number of patients with serious adverse events occurring during the treatment period was similar in the two groups (413 patients [27.0%] in the ferric carboxymaltose group and 401 [26.2%] in the placebo group)., Conclusions: Among ambulatory patients who had heart failure with a reduced ejection fraction and iron deficiency, there was no apparent difference between ferric carboxymaltose and placebo with respect to the hierarchical composite of death, hospitalizations for heart failure, or 6-minute walk distance. (Funded by American Regent, a Daiichi Sankyo Group company; HEART-FID ClinicalTrials.gov number, NCT03037931.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Iron-deficiency anemia is common in inflammatory bowel disease, requiring oral or intravenous iron replacement therapy. Treatment with standard oral irons is limited by poor absorption and gastrointestinal toxicity. Ferric maltol is an oral iron designed for improved absorption and tolerability., Methods: In this open-label, phase 3b trial (EudraCT 2015-002496-26 and NCT02680756), adults with nonseverely active inflammatory bowel disease and iron-deficiency anemia (hemoglobin, 8.0-11.0/12.0 g/dL [women/men]; ferritin, <30 ng/mL/<100 ng/mL with transferrin saturation <20%) were randomized to oral ferric maltol 30 mg twice daily or intravenous ferric carboxymaltose given according to each center's standard practice. The primary endpoint was a hemoglobin responder rate (≥2 g/dL increase or normalization) at week 12, with a 20% noninferiority limit in the intent-to-treat and per-protocol populations., Results: For the intent-to-treat (ferric maltol, n = 125/ferric carboxymaltose, n = 125) and per-protocol (n = 78/88) analyses, week 12 responder rates were 67% and 68%, respectively, for ferric maltol vs 84% and 85%, respectively, for ferric carboxymaltose. As the confidence intervals crossed the noninferiority margin, the primary endpoint was not met. Mean hemoglobin increases at weeks 12, 24, and 52 were 2.5 vs 3.0 g/dL, 2.9 vs 2.8 g/dL, and 2.7 vs 2.8 g/dL with ferric maltol vs ferric carboxymaltose. Treatment-emergent adverse events occurred in 59% and 36% of patients, respectively, and resulted in treatment discontinuation in 10% and 3% of patients, respectively., Conclusions: Ferric maltol achieved clinically relevant increases in hemoglobin but did not show noninferiority vs ferric carboxymaltose at week 12. Both treatments had comparable long-term effectiveness for hemoglobin and ferritin over 52 weeks and were well tolerated., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Anaemia is common and associated with poor outcomes in survivors of critical illness. However, the optimal treatment strategy is unclear., Methods: We conducted a multicentre, feasibility RCT to compare either a single dose of ferric carboxymaltose 1000 mg i.v. or usual care in patients being discharged from the ICU with moderate or severe anaemia (haemoglobin ≤100 g L -1 ). We collected data on feasibility (recruitment, randomisation, follow-up), biological efficacy, and clinical outcomes., Results: Ninety-eight participants were randomly allocated (49 in each arm). The overall recruitment rate was 34% with 6.5 participants recruited on average per month. Forty-seven of 49 (96%) participants received the intervention. Patient-reported outcome measures were available for 79/93 (85%) survivors at 90 days. Intravenous iron resulted in a higher mean (standard deviation [sd]) haemoglobin at 28 days (119.8 [13.3] vs 106.7 [14.9] g L -1 ) and 90 days (130.5 [15.1] vs 122.7 [17.3] g L -1 ), adjusted mean difference (10.98 g L -1 ; 95% confidence interval [CI], 4.96-17.01; P<0.001) over 90 days after randomisation. Infection rates were similar in both groups. Hospital readmissions at 90 days post-ICU discharge were lower in the i.v. iron group (7/40 vs 15/39; risk ratio=0.46; 95% CI, 0.21-0.99; P=0.037). The median (inter-quartile range) post-ICU hospital stay was shorter in the i.v. iron group but did not reach statistical significance (5.0 [3.0-13.0] vs 9.0 [5.0-16.0] days, P=0.15)., Conclusion: A large, multicentre RCT of i.v. iron to treat anaemia in survivors of critical illness appears feasible and is necessary to determine the effects on patient-centred outcomes., Clinical Trial Registration: ISRCTN13721808 (www.isrctn.com)., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: We investigated whether routine perioperative intravenous iron replenishment reduces the requirement for packed erythrocytes (pRBC) transfusion., Summary of Background Data: Patients undergoing complex cardiac surgery are at high risk of developing postoperative iron deficiency anemia, thus requiring transfusion, which is associated with adverse outcomes., Methods: Patients were randomized to receive either ferric derisomaltose 20 mg/kg (n = 103) or placebo (n = 101) twice during the perioperative period: 3 days before and after the surgery. The primary endpoint was the proportion of patients who received pRBC transfusion until postoperative day (POD) 10. Hemoglobin, reticulocyte count, serum iron profile, hepcidin, and erythropoietin were serially measured., Results: pRBC was transfused in 60.4% and 57.2% of patients in the control and iron group, respectively (P = 0.651). Hemoglobin concentration at 3 weeks postoperatively was higher in the iron group than in the control group (11.6 ± 1.5 g/dL vs 10.9 ± 1.4 g/dL, P < 0.001). The iron group showed higher reticulocyte count [205 (150-267)×103/μL vs 164 (122-207)×103/μL, P = 0.003] at POD 10. Transferrin saturation and serum ferritin were significantly increased in the iron group than in the control group (P < 0.001). Serum hepcidin was higher in the iron group than in the control group at POD 3 [106.3 (42.9-115.9) ng/mL vs 39.3 (33.3-43.6) ng/mL, P < 0.001]. Erythropoietin concentration increased postoperatively in both groups (P = 0.003), with no between-group difference., Conclusions: Intravenous iron supplementation during index hospitalization for complex cardiac surgery did not minimize pRBC transfusion despite replenished iron store and augmented erythropoiesis, which may be attributed to enhanced hepcidin expression., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients suffering from heart failure (HF) and iron deficiency (ID) have worse outcomes. Treatment with intra-venous (IV) ferric carboxymaltose has been shown to reduce HF rehospitalizations and to improve functional capacity and symptoms in patients with HF and reduced ejection fraction (HFrEF). However, IV ferric carboxymaltose is significantly more expensive than IV sodium ferric gluconate complex (SFGC) limiting its availability to most HF patients around the globe. Methods: A retrospective analysis comparing patients admitted to internal medicine or cardiology departments between January 2013 to December 2018 due to acute decompensated HF (ADHF) and treated with or without IV SFGC on top of standard medical therapy. Results: During the study period, a total of 1863 patients were hospitalized due to ADHF with either HFrEF or HF with preserved ejection fraction (HFpEF). Among them, 840 patients had laboratory evidence of iron deficiency (absolute or functional) and met the inclusion criteria. One hundred twenty-two of them (14.5%) were treated with IV SFGC during the index hospitalization. Patients treated with IV iron were more likely to have history of ischemic heart disease, atrial fibrillation, and chronic kidney disease. The rate of readmissions due to ADHF was similar between the groups at 30 days, 3 months, and 1 year. Conclusion: High risk patient hospitalized to ADHF and treated with IV SFGC showed comparable ADHF readmission rates, compared to those who did not receive iron supplementation.

Erythropoiesis-stimulating agents (ESA) are effective for chemotherapy-induced anemia (CIA) but associated with serious adverse events. Safer alternatives would be beneficial in this population. The efficacy and safety of ferric carboxymaltose (FCM) as monotherapy for CIA was evaluated. This Phase 3, 18-week, double-blind, placebo-controlled study randomized adults with ≥ 4 weeks of chemotherapy remaining for treatment of nonmyeloid malignancies with CIA to FCM (two 15 mg/kg infusions 7 days apart; maximum dose, 750 mg single/1500 mg total) or placebo. The primary efficacy endpoint was percentage of patients with decreases in hemoglobin (Hb) ≥ 0.5 g/dL from weeks 3 to 18; the key secondary efficacy endpoint was change in Hb from baseline to week 18. Inclusion criteria included: (Hb) 8-11 g/dL, ferritin 100-800 ng/mL, and transferrin saturation (TSAT) ≤35%. In 244 patients (n = 122, both groups), the percent of patients who maintained Hb within 0.5 g/dL of baseline from weeks 3 to 18 was significantly higher with FCM versus placebo (50.8% vs. 35.3%; p = 0.01). Mean change in Hb from baseline to week 18 was similar between FCM and placebo (1.04 vs. 0.87 g/dL) but significantly greater with FCM with baseline Hb ≤ 9.9 g/dL (1.08 vs. 0.42 g/dL; p = 0.01). The percent with ≥ 1 g/dL increase from baseline was significantly higher with FCM versus placebo (71% vs. 54%; p = 0.01), occurring in a median 43 versus 85 days (p = 0.001). Common adverse events in the FCM arm included neutropenia (17%), hypophosphatemia (16%), and fatigue (15%). FCM monotherapy effectively maintained Hb and was well tolerated in CIA., (© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Introduction: Hyperphosphatemia is a common complication as chronic kidney disease (CKD) progresses and most patients undergoing dialysis are prescribed oral phosphate binder therapy to control serum phosphate concentrations. Sucroferric oxyhydroxide is an iron-based phosphate binder approved for the treatment of hyperphosphatemia in CKD patients on dialysis., Areas Covered: This article reviews key safety and effectiveness data for sucroferric oxyhydroxide from both prospective clinical trials and real-world observational studies., Expert Opinion: Sucroferric oxyhydroxide potently binds dietary phosphate in the gastrointestinal (GI) tract, resulting in effective reduction of serum phosphate concentrations with a relatively low daily pill burden. Data from clinical trials and real-world observational studies show sucroferric oxyhydroxide has a favorable safety and tolerability profile. The most frequent side effects observed with sucroferric oxyhydroxide are GI-related, mainly discolored (black) stools and mild or moderate transient diarrhea, both of which are manageable. There is minimal systemic iron absorption from sucroferric oxyhydroxide, and therefore the drug is associated with a low risk of iron accumulation. Sucroferric oxyhydroxide also displays low potential for drug-drug interactions with other commonly prescribed oral medications. Overall, sucroferric oxyhydroxide offers an effective and well-tolerated treatment option for the management of hyperphosphatemia.

Obesity is associated with an increased risk of an iron deficiency; however, a synergistic relationship between iron and lipid homeostasis was also observed. The aim of this study was to investigate the effects of pharmacological doses of iron supplementation on omega 3 (n-3) and omega 6 (n-6) polyunsaturated fatty acids (PUFAs). Sprague-Dawley (SD) rats were fed a normal diet or a 50% high-fat diet (HFD) without or with pharmacological doses of ferric citrate (0.25, 1, or 2 g ferric iron per kg diet) for 12 weeks, and erythrocyte profiles of n-3 and n-6 PUFAs were quantitated. Ferric citrate supplementation showed dose-related effects on liver inflammation, liver iron accumulation, and increasing circulating levels of iron, erythrocyte degradation biomarkers LVV-hemorphin-7, malondialdehyde (MDA), and insulin. Obese rats supplemented with 2 g ferric iron per kg diet also had decreased levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and total n-3 PUFAs compared to rats fed a normal diet or HFD alone. A western blotting analysis revealed that iron-mediated downregulation of n-3 PUFA-converting enzymes (Δ5 and Δ6 desaturases) only occurred at high dosages (≥1 g ferric iron per kg diet). A Spearman correlation analysis showed that total liver iron and serum LVV-hemorphin-7 and MDA were negatively correlated with n-3 PUFAs and their converting enzymes (Δ5 and Δ6 desaturases) (all p < 0.05). In conclusion, obese rats that received high-dose ferric citrate supplementation (>1 g of ferric iron per kg diet) exhibited decreased n-3 PUFA levels via downregulation of expressions of Δ5 and Δ6 desaturase enzymes.

Background: Fibroblast growth factor-23 (FGF23) and α-klotho are associated with anemia in patients with chronic kidney disease. In this post hoc analysis of the ASTRIO study (UMIN000019176), we investigated the relationship between FGF23 and α-klotho during treatment with an iron-based phosphate binder, ferric citrate hydrate (FC), compared with non-iron-based phosphate binders in hemodialysis (HD) patients. We examined the effect of iron absorption by FC on the relationship between FGF23 and α-klotho. There have been few clinical studies evaluating these biomarkers simultaneously in HD patients., Methods: The ASTRIO study was a 24-week, randomized, open-label, multicenter trial. HD patients taking non-iron-based phosphate binder(s) were randomized at a 1:1 ratio to continue other binder(s) (control group) or switch to FC (FC group). Serum phosphate (P) and hemoglobin (Hb) were maintained within 3.5-6.0 mg/dL and 10-12 g/dL, respectively. Plasma levels of intact FGF23 (i-FGF23), C-terminal FGF23 (c-FGF23), and α-klotho were measured, as were iron-related parameters. Association analyses of FGF23 and α-klotho were conducted., Results: Patients were randomized to FC (n = 48) and control (n = 45) groups. Serum ferritin significantly increased from baseline to end-of-treatment (EOT) in the FC group, compared with the control group (adjusted mean difference [95% confidence interval]: 79.5 [44.7, 114.4] ng/mL; p <  0.001). The mean change from baseline to EOT in c-FGF23 was significantly different between the FC and control groups (mean ± standard deviation (SD): - 0.2 ± 0.8 log e pg/mL vs. 0.2 ± 0.8 log e pg/mL, respectively; p = 0.04). The mean change from baseline to EOT in i-FGF23 and α-klotho were not significantly different between the FC and control groups (mean ± SD: - 0.1 ± 0.8 log e pg/mL vs. 0.1 ± 0.9 log e pg/mL; p = 0.33, and 2.0 ± 91.5 pg/mL vs. - 8.9 ± 145.3; p = 0.58, respectively). However, both forms of FGF23 and α-klotho were not significantly associated with each other in both groups., Conclusions: Iron absorbed via FC administration in HD patients did not influence the correlation relationship between plasma levels of FGF23 and α-klotho under the condition of serum P and Hb were maintained., Trial Registration: ASTRIO study ( UMIN000019176 , registered at UMIN Clinical Trials Registry on October 1, 2015)., (© 2021. The Author(s).)