Iron Deficiency, Anemia, and Iron Supplementation in Patients With Heart Failure: A Population-Level Study.

BACKGROUND: Studies have shown an association between iron deficiency (ID) and clinical outcomes in patients with heart failure (HF), irrespective of the presence of ID anemia (IDA). The current study used population-level data from a large, single-payer health care system in Canada to investigate the epidemiology of ID and IDA in patients with acute HF and those with chronic HF, and the iron supplementation practices in these settings. METHODS: All adult patients with HF in Alberta between 2012 and 2019 were identified and categorized as acute or chronic HF. HF subtypes were determined through echocardiography data, and ID (serum ferritin concentration <100 µg/L, or ferritin concentration between 100 and 300 µg/L along with transferrin saturation <20%), and IDA through laboratory data. Broad eligibility for 3 clinical trials (AFFIRM-AHF [Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute HF and ID], IRONMAN [Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency], and HEART-FID [Randomized Placebocontrolled Trial of Ferric Carboxymaltose as Treatment for HF With ID]) was determined. RESULTS: Among the 17 463 patients with acute HF, 38.5% had iron studies tested within 30 days post-index-HF episode (and 34.2% of the 11 320 patients with chronic HF). Among tested patients, 72.6% of the acute HF and 73.9% of the chronic HF were iron-deficient, and 51.4% and 49.0% had IDA, respectively. Iron therapy was provided to 41.8% and 40.5% of patients with IDA and acute or chronic HF, respectively. Of ID patients without anemia, 19.9% and 21.7% were prescribed iron therapy. The most common type of iron therapy was oral (28.1% of patients). Approximately half of the cohort was eligible for each of the AFFIRM-AHF, intravenous iron treatment in patients with HF and ID, and HEART-FID trials. CONCLUSIONS: Current practices for investigating and treating ID in patients with HF do not align with existing guideline recommendations. Considering the gap in care, innovative strategies to optimize iron therapy in patients with HF are required.

The magnitude of the plasma hepcidin response to oral iron supplements depends on the iron dosage.

BACKGROUND: Iron deficiency without anaemia is a common health problem, especially in young menstruating women. The efficacy of the usually recommended oral iron supplementation is limited due to increased plasma hepcidin concentration, which reduces iron absorption and leads to side effects such as intestinal irritation. This observation raises the question of how low-dose iron therapy may affect plasma hepcidin levels and whether oral iron intake dose-dependently affects plasma hepcidin production. METHODS: Fifteen non-anaemic women with iron deficiency (serum ferritin ≤30 ng/ml) received a single dose of 0, 6, 30, or 60 mg of elemental oral iron as ferrous sulfate on different days. Plasma hepcidin was measured before and seven hours after each dose. RESULTS: Subjects had an average age of 23 (standard deviation = 3.0) years and serum ferritin of 24 ng/ml (interquartile range = 16-27). The highest mean change in plasma hepcidin levels was measured after ingesting 60 mg of iron, increasing from 2.1 ng/ml (interquartile range = 1.6-2.9) to 4.1 ng/ml (interquartile range = 2.5-6.9; p < 0.001). Iron had a significant dose-dependent effect on the absolute change in plasma hepcidin (p = 0.008), where lower iron dose supplementation resulted in lower plasma hepcidin levels. Serum ferritin levels were significantly correlated with fasting plasma hepcidin levels (R2 = 0.504, p = 0.003) and the change in plasma hepcidin concentration after iron intake (R2 = 0.529, p = 0.002). CONCLUSION: We found a dose-dependent effect of iron supplementation on plasma hepcidin levels. Lower iron dosage results in a smaller increase in hepcidin and might thus lead to more efficient intestinal iron absorption and fewer side effects. The effectiveness and side effects of low-dose iron treatment in women with iron deficiency should be further investigated. This study was registered at the Swiss National Clinical Trials Portal (2021-00312) and ClinicalTrials.gov (NCT04735848).

Imbalanced and Unchecked: The Role of Metal Dyshomeostasis in Driving COPD Progression.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by persistent inflammation and oxidative stress, which ultimately leads to progressive restriction of airflow. Extensive research findings have cogently suggested that the dysregulation of essential transition metal ions, notably iron, copper, and zinc, stands as a critical nexus in the perpetuation of inflammatory processes and oxidative damage within the lungs of COPD patients. Unraveling the intricate interplay between metal homeostasis, oxidative stress, and inflammatory signaling is of paramount importance in unraveling the intricacies of COPD pathogenesis. This comprehensive review aims to examine the current literature on the sources, regulation, and mechanisms by which metal dyshomeostasis contributes to COPD progression. We specifically focus on iron, copper, and zinc, given their well-characterized roles in orchestrating cytokine production, immune cell function, antioxidant depletion, and matrix remodeling. Despite the limited number of clinical trials investigating metal modulation in COPD, the advent of emerging methodologies tailored to monitor metal fluxes and gauge responses to chelation and supplementation hold great promise in unlocking the potential of metal-based interventions. We conclude that targeted restoration of metal homeostasis represents a promising frontier for ameliorating pathological processes driving COPD progression.

A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.

Immediate postpartum anemia and associated factors at shewarobit health facilities, Amhara, Ethiopia, 2022: a cross sectional study.

BACKGROUND: Immediate postpartum anemia occurs when the amount of red blood cell count is reduced or hemoglobin concentration is below 10 g/dl in the immediate postpartum. It occurs primarily due to inadequate iron intake before and during pregnancy and blood loss during delivery. The aim of this study is to assess the proportion of immediate postpartum anemia and associated factors among mothers who gave birth at Shewarobit health facilities; in Amhara, Ethiopia. METHODS: Institutional-based cross-sectional study was conducted from June to September 2022. A systematic random sampling method was employed to select the study participants. The data were collected through interviewer-assisted questions. Data were entered into Epi Data software version 4.6.0.4 and exported to SPSS 21 for analysis, and descriptive statistics were computed. Logistic regression was applied, and P-values less than 0.05 were considered statistically significant. RESULTS: This study was conducted among 307 study participants and, the proportion of immediate postpartum anemia was 41.4% [95% CI: 36.7-46.6]. Having postpartum hemorrhage [AOR = 4.76, 95% CI: 2.44-9.28], not taking iron and folic acid supplementation [AOR = 6.19, 95% CI: 2.69, 14.22], having a prolonged second stage of labor [AOR = 2.52, 95% CI: 1.16-5.44], and mid-upper arm circumference < 23 cm [AOR = 2.02, 95% CI: 1.11-3.68] were factors significantly associated with immediate postpartum anemia. CONCLUSIONS: The proportion of immediate postpartum anemia was public problem in Shewarobit health facilities. Following the progress of labor using a partograph, closely monitoring and immediate intervention of PPH, and prevent undernutrition during antenatal care is recommended.

Iron therapy supplementation in inflammatory bowel disease patients with iron deficiency anemia: findings from a real-world analysis in Italy.

BACKGROUND: This real-world analysis evaluated iron therapy supplementation in inflammatory bowel disease patients with iron-deficiency anemia, considering disease progression and healthcare resource consumption. METHODS: A retrospective observational study was conducted using administrative databases of a pool of Italian healthcare entities, covering about 9.3 million beneficiaries. Between January 2010 and September 2017, adult patients were enrolled in the presence of either hospitalization or active exemption code for ulcerative colitis/Crohn's disease, or one vedolizumab prescription. Iron-deficiency anemia was identified by at least one prescription for iron and/or hospitalization for iron-deficiency anemia and/or blood transfusion (proxy of diagnosis). Patients were divided in untreated and iron-treated during 12-month follow-up and analyzed before and after propensity score matching. Disease progression, was evaluated through inflammatory bowel disease-related hospitalizations and surgeries, and healthcare resource utilization was assessed. RESULTS: Overall, 1753 patients were included, 1077 (61.4%) treated with iron therapy and 676 (38.6%) untreated. After propensity score matching, 655 patients were included in each group. In unbalanced cohorts, disease progression was significantly reduced in patients receiving iron therapy compared to the untreated (11.0% vs. 15.7%, P  < 0.01), and this trend was maintained also after applying propensity score matching. The overall mean cost/patient was significantly lower in iron-treated than untreated (4643€ vs. 6391€, P  < 0.01). CONCLUSION: The findings of this real-world analysis suggest that iron therapy was associated with significant benefits in inflammatory bowel disease patients with iron-deficiency anemia, in terms of both disease progression and healthcare resource utilization.

Compliance With NCCN Guidelines for Evaluation and Treatment of Anemia Among Patients With Solid Tumors.

BACKGROUND: NCCN Guidelines for Hematopoietic Growth Factors recommend evaluation and treatment of anemia in patients with cancer. However, a paucity of data exists regarding compliance with these recommendations. METHODS: A retrospective cohort study was performed of patients diagnosed with any solid tumor at Vanderbilt University Medical Center from 2008 to 2017. Tumor registry-confirmed cancer cases were identified by ICD-O codes using the Synthetic Derivative database. Anemia was defined as hemoglobin (Hgb) level ≤11 g/dL and graded according to CTCAE version 5.0. Absolute, functional, and possible functional iron deficiency were defined based on NCCN Guidelines. RESULTS: A total of 25,018 patients met inclusion criteria. Median age was 60 years. The most common malignancies were respiratory tract, prostate, and nonprostate urologic (11% each). Among 8,695 patients with Hgb levels available prior to diagnosis, 1,484 (17%) were noted to be anemic proximal to diagnosis. Of the 25,018 patients, 11,019 (44%) were anemic within 6 months of diagnosis. Of these patients, 4,686 (43%) had grade 2 (moderate) anemia and 9,623 (87%) had normocytic anemia. Patients with retroperitoneal/peritoneal cancers had the highest prevalence of anemia (83/110; 75%). A total of 4,125 (37%) underwent any evaluation of their anemia, of whom 1,742 (16%) had iron studies performed and 1,528 (14%) had vitamin B12 or folate studies performed. Fewer than half of patients with anemia received treatment (n=4,318; 39%), including blood transfusion (n=3,528; 32%), oral iron supplementation (n=1,279; 12%), or intravenous iron supplementation (n=97; 1%). Anemia treatment was significantly more frequent as the grade of anemia increased (any treatment among grade 1/mild: 12%; grade 2/moderate: 31%; grade 3/severe: 77%; χ2 [2, n=11,019]=3,020.6; P<.001). Patients with penile and testicular cancers had the highest prevalence of anemia evaluation (n=57; 79%). CONCLUSIONS: Anemia is common in patients with solid tumors; yet, compliance with NCCN Guidelines for evaluation and treatment of anemia remains low. There are opportunities to improve compliance with guidelines across the spectrum of cancer care.

Association between Iron-Folic Acid Supplementation during Pregnancy and Maternal and Infant Anemia in West Java, Indonesia: A Mixed-Method Prospective Cohort Study.

The Indonesian government has provided iron-folic acid (IFA) supplementation in response to maternal pregnancy iron-deficiency anemia. However, community-based cohorts on IFA's effects on maternal and infant anemia are limited. A mixed-method study design with a primary longitudinal cohort was used to observe the association between IFA and anemia in mothers and infants. Iron-folic acid supplementation was observed throughout pregnancy. Anemia status was based on a single hemoglobin assessment using HemoCue Hb 201 + in the second or third trimester of pregnancy for the mother and at birth for the infant. Qualitative data were collected via in-depth interviews (IDIs) and a forum group discussion (FGD). Iron-folic acid supplementation with > 180 tablets throughout pregnancy was associated with lower pregnancy anemia (adjusted relative risk [aRR] = 0.25, 95% CI: 0.092-0.664, P = 0.006) after adjusting for potential confounding variables. Supplementation with IFA was not associated with infant anemia (RR = 1.033, 95% CI: 0.70-1.54, P = 0.873 for 90-180 tablets and RR = 1.07, 95% CI 0.70-1.63, P = 0.774 for > 180 tablets). The IDIs and FGD suggested that IFA and multivitamin content knowledge, IFA consumption monitoring, and paternal involvement were important in IFA supplementation and effectiveness in reducing anemia. Iron-folic acid supplementation was associated with reduced maternal but not infant anemia. Because maternal anemia is associated with infant anemia, an anemia monitoring program for women in early pregnancy is vital in addressing infant health. Paternal involvement was also identified as a major factor in maternal and child health.

Should echocardiogram be undertaken routinely when a child has severe iron deficiency anaemia?

Iron deficiency anaemia (IDA) is common in children. Treatment usually consists of oral iron therapy and, if severe, inpatient hospitalisation with blood transfusion. Providers may also undertake an echocardiogram, depending on availability and the severity of anaemia. A male toddler with nutritional IDA, haemoglobin of 1.7 g/dL (the lowest level in the literature) and hypertension had left ventricular hypertrophy (LVH) on the initial echocardiogram. He was managed acutely with judicious blood transfusion, followed by oral iron supplementation and anti-hypertensive medication at discharge. Repeat echocardiogram a month later demonstrated slight improvement of the LVH but the hypertension persisted at follow-up 6 months later. There was complete resolution of the findings a year later. In chronic nutritional IDA, there can be structural cardiac changes which can affect the acute management and requires close follow-up. It is important to use echocardiography in such severe cases.Abbreviations: CHF: congestive heart failure; CM: cardiomyopathy; DCM: dilated cardiomyopathy; ICU: intensive care unit; IDA: iron deficiency anaemia; IVSd: interventricular septum in diastole; LA: left atrium; LV: left ventricle; LVEDD: left ventricular end-diastolic diameter; LVH: left ventricular hypertrophy; LVM: left ventricular mass; LVPWd: left ventricular posterior wall end-diastole; PRBC: packed red blood cells.

Current concepts in postpartum anemia management.

PURPOSE OF REVIEW: Postpartum anemia (PPA) is common in women after childbirth and affects about 50-80% of all women worldwide. Iron deficiency (ID) is the main cause for anemia and constitutes a potentially preventable condition with great impact on the mother's physical and mental condition after delivery. In most cases, PPA is associated with antenatal ID and peripartum blood losses. Numerous published studies confirmed the positive effect of PPA diagnosis and treatment. RECENT FINDINGS: Iron deficiency as well as iron deficiency anemia (IDA) are common in the postpartum period and represent significant health problems in women of reproductive age. SUMMARY: Important movements towards early detection and therapy of postpartum anemia have been observed. However, postpartum anemia management is not implemented on a large scale as many healthcare professionals are not aware of the most recent findings in the field. Diagnosis and therapy of PPA, particularly iron supplementation in ID and IDA, has proven to be highly effective with a tremendous effect on women's wellbeing and outcome.

An in vitro evaluation of the effects of fluoride, CPP-ACP, or resin infiltration on discoloration caused by pediatric supplements.

OBJECTIVES: White spot lesions are more susceptible to staining agents due to their porous structure. This study examines the impact of white spot lesion treatments on discoloration caused by pediatric supplements. METHOD AND MATERIALS: Three treatments (fluoride, casein phosphopeptide-amorphous calcium phosphate [CPP-ACP], resin infiltration), a control, and their respective syrup-based subgroups (iron and black elderberry syrups) were established, each with eight teeth. Artificial white spot lesions were induced, and weekly applications of fluoride varnish, daily applications of CPP-ACP paste, or a single resin infiltration procedure were performed on the white spot lesions within the treatment groups over 4 weeks. Simultaneously, samples were exposed daily to iron or black elderberry syrups. Spectrophotometer measurements were taken at baseline, after demineralization (T0), and after 1 (T1), 2 (T2), and 4 weeks (T4). ΔE00 values were calculated. Statistical analysis was conducted using a three-way mixed-design ANOVA, with the significance level set at P = .05. RESULTS: At T4, ΔE00 values from all groups exceeded the clinical acceptability limit of 1.8. At T2 and T4, the ΔE00 values obtained from the black elderberry syrup subgroups were significantly higher (P < .001). At T4, the highest ΔE00 values were seen in the CPP-ACP groups (P < .001). The lowest ΔE00 values at T2 and T4 were observed in the resin infiltration groups (P < .05). CONCLUSIONS: Supplements containing ferrous sulfate and black elderberry extract caused color changes in white spot lesions that exceeded the clinical acceptability limit. Resin infiltration of white spot lesions provides advantages over remineralization treatments, particularly in minimizing discoloration induced by pediatric supplements.

Reported outcomes in patients with iron deficiency or iron deficiency anemia undergoing major surgery: a systematic review of outcomes.

BACKGROUND: Iron deficiency (ID) is the leading cause of anemia worldwide. The prevalence of preoperative ID ranges from 23 to 33%. Preoperative anemia is associated with worse outcomes, making it important to diagnose and treat ID before elective surgery. Several studies indicated the effectiveness of intravenous iron supplementation in iron deficiency with or without anemia (ID(A)). However, it remains challenging to establish reliable evidence due to heterogeneity in utilized study outcomes. The development of a core outcome set (COS) can help to reduce this heterogeneity by proposing a minimal set of meaningful and standardized outcomes. The aim of our systematic review was to identify and assess outcomes reported in randomized controlled trials (RCTs) and observational studies investigating iron supplementation in iron-deficient patients with or without anemia. METHODS: We searched MEDLINE, CENTRAL, and ClinicalTrials.gov systematically from 2000 to April 1, 2022. RCTs and observational studies investigating iron supplementation in patients with a preoperative diagnosis of ID(A), were included. Study characteristics and reported outcomes were extracted. Outcomes were categorized according to an established outcome taxonomy. Quality of outcome reporting was assessed with a pre-specified tool. Reported clinically relevant differences for sample size calculation were extracted. RESULTS: Out of 2898 records, 346 underwent full-text screening and 13 studies (five RCTs, eight observational studies) with sufficient diagnostic inclusion criteria for iron deficiency with or without anemia (ID(A)) were eligible. It is noteworthy to mention that 49 studies were excluded due to no confirmed diagnosis of ID(A). Overall, 111 outcomes were structured into five core areas including nine domains. Most studies (92%) reported outcomes within the 'blood and lymphatic system' domain, followed by "adverse event" (77%) and "need for further resources" (77%). All of the latter reported on the need for blood transfusion. Reported outcomes were heterogeneous in measures and timing. Merely, two (33%) of six prospective studies were registered prospectively of which one (17%) showed no signs of selective outcome reporting. CONCLUSION: This systematic review comprehensively depicts the heterogeneity of reported outcomes in studies investigating iron supplementation in ID(A) patients regarding exact definitions and timing. Our analysis provides a systematic base for consenting to a minimal COS. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020214247.

Predicting response to iron supplementation in patients with active inflammatory bowel disease (PRIme): a randomised trial protocol.

INTRODUCTION: Iron deficiency anaemia (IDA) is the most common systemic manifestation of inflammatory bowel disease (IBD) that has detrimental effects on quality of life (QoL) and disease outcomes. Iron deficiency (ID), with or without anaemia, poses a diagnostic and therapeutic challenge in patients with IBD due to the multifactorial nature of ID(A) and its frequent recurrence. Elevated hepcidin-a systemic iron regulator that modulates systemic iron availability and intestinal iron absorption-has been associated with oral iron malabsorption in IBD. Therefore, hepcidin could assist in therapeutic decision-making. In this study, we investigate whether hepcidin can predict response to oral and intravenous iron supplementation in patients with active IBD undergoing anti-inflammatory treatment. METHODS AND ANALYSIS: PRIme is an exploratory, multicentre, open-label and randomised trial. All adult patients with active IBD and ID(A) will be assessed for eligibility. The participants (n=90) will be recruited at five academic hospitals within the Netherlands and randomised into three groups (1:1:1): oral ferrous fumarate, oral ferric maltol or intravenous iron. Clinical and biochemical data will be collected at the baseline and after 6, 14 and 24 weeks. Blood samples will be collected to measure hepcidin and other biomarkers related to iron status. In addition, patient-reported outcomes regarding QoL and disease burden will be evaluated. The primary outcome is the utility of hepcidin as a predictive biomarker for response to iron therapy, which will be assessed using receiver operating curve analysis. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board at the Leiden University Medical Center (IRB No. P21.109) and other study sites. All participants will provide written informed consent to enrol in the study. The findings will be published in a peer-reviewed journal and disseminated at scientific conferences; the dataset will be available on reasonable request. TRIAL REGISTRATION: Prospectively registered in the https://clinicaltrials.gov/ and the Eudra registries. First submitted on 10 May 2022 to the ClinicalTrials.gov (ID: NCT05456932) and on 3 March 2022 to the European Union Drug Regulating Authorities Clinical Trials Database (ID: 2022-000894-16).

Targeting of FSP1 regulates iron homeostasis in drug-tolerant persister head and neck cancer cells via lipid-metabolism-driven ferroptosis.

BACKGROUND: Research has demonstrated that some tumor cells can transform into drug-tolerant persisters (DTPs), which serve as a reservoir for the recurrence of the disease. The persister state in cancer cells arises due to temporary molecular reprogramming, and exploring the genetic composition and microenvironment during the development of head and neck squamous cell carcinoma (HNSCC) can enhance our comprehension of the types of cell death that HNSCC, thus identifying potential targets for innovative therapies. This project investigated lipid-metabolism-driven ferroptosis and its role in drug resistance and DTP generation in HNSCC. METHODS: High levels of FSP1 were discovered in the tissues of patients who experienced relapse after cisplatin treatment. RNA sequencing indicated that a series of genes related to lipid metabolism were also highly expressed in tissues from these patients. Consistent results were obtained in primary DTP cells isolated from patients who experienced relapse. The Cancer Genome Atlas database confirmed this finding. This revealed that the activation of drug resistance in cancer cells is influenced by FSP1, intracellular iron homeostasis, and lipid metabolism. The regulatory roles of ferroptosis suppressor protein 1 (FSP1) in HNSCC metabolic regulation were investigated. RESULTS: We generated human oral squamous cell carcinoma DTP cells (HNSCC cell line) to cisplatin and observed higher expression of FSP1 and lipid-metabolism-related targets in vitro. The shFSP1 blockade attenuated HNSCC-DTP cell stemness and downregulated tumor invasion and the metastatic rate. We found that cisplatin induced FSP1/ACSL4 axis expression in HNSC-DTPC cells. Finally, we evaluated the HNSCC CSC-inhibitory functions of iFSP1 (a metabolic drug and ferroptosis inducer) used for neo-adjuvant chemotherapy; this was achieved by inducing ferroptosis in a patient-derived xenograft mouse model. CONCLUSIONS: The present findings elucidate the link between iron homeostasis, ferroptosis, and cancer metabolism in HNSCC-DTP generation and acquisition of chemoresistance. The findings may serve as a suitable model for cancer treatment testing and prediction of precision treatment outcomes. In conclusion, this study provides clinically oriented platforms for evaluating metabolism-modulating drugs (FSP1 inhibitors) and new drug candidates of drug resistance and ferroptotic biomarkers.

Management of Preoperative Anemia.

Anemia is the most common modifiable risk factor for postoperative morbidity and mortality. Early identification and optimal management are key to restore iron stores and ensure its resolution before surgery. Several therapies have been proposed to treat anemia in the perioperative period, such as iron supplementation and erythropoiesis-stimulating agents, though it remains unclear which is the most optimal to improve clinical outcomes. This article summarizes the most updated evidence on perioperative management of anemia and denotes differences among the international guidelines to reflect the conflicting evidence in this field and the need for further research in specific areas.

Sensory evaluations of a novel iron and zinc-enriched powder for the potential treatment and prevention of iron deficiency in women of reproductive age.

Iron deficiency (ID) and ID with anaemia (IDA) are serious global health problems that disproportionately affect women aged 15-49 years. Although food fortification is one of the most effective and sustainable ways to combat nutritional deficiencies, iron remains one of the most difficult micronutrients to fortify, given its tendency to react strongly with food constituents. Therefore, it is important to assess the sensory properties of foods fortified with iron to determine the acceptability and palatability in target populations. We aimed to determine the palatability and acceptability of a novel iron and zinc-enriched powder fortified in tap water by conducting sensory evaluations in 35 women of reproductive age using a 9-point hedonic scale, where participants rated the sensory properties of six samples containing different amounts of the active or placebo powder. We found significant differences between samples reconstituted at 1, 2, and 3 g/L for sensory properties, including overall taste. Participants were found to be more willing to drink the mineral-enriched powder when prepared at the lowest concentration (1 g/L) compared to higher concentrations. Our results provide important insight into the sensory qualities of a novel formulation of an iron and zinc-enriched powder for at-home fortification and indicate consumer acceptability in reproductive-aged women, a key group at risk for ID/IDA. If found to improve iron status, novel treatments like this product will contribute to global efforts to develop safe, acceptable and sustainable interventions for ID and IDA.

Compassionate use of roxadustat for treatment of refractory renal anemia in an infant.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) have played an important role in the treatment of renal anemia in children, but cannot improve hemoglobin to target level in some cases. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, can stimulate endogenous erythropoietin production and regulate iron metabolism even in patients with kidney failure. However, roxadustat has not yet been approved for use in children. CASE-DIAGNOSIS/TREATMENT: We report a case of refractory renal anemia in an 80-day-old boy, who was hyporesponsive to ESAs even in combination with iron supplementation and transfusion. Compassionate use of roxadustat successfully corrected the intractable anemia. Hyperkalemia is a manageable adverse event of concern during follow-up. CONCLUSION: The successful experience in this case may inform the clinical utility of roxadustat for refractory renal anemia in children, which should be further confirmed by well-designed prospective clinical trials.

Iron Deficiency Anemia: An Updated Review.

BACKGROUND: Worldwide, iron deficiency anemia is the most prevalent nutritional deficiency disorder and the leading cause of anemia in children, especially in developing countries. When present in early childhood, especially if severe and prolonged, iron deficiency anemia can result in neurodevelopmental and cognitive deficits, which may not always be fully reversible even following the correction of iron deficiency anemia. OBJECTIVE: This article aimed to familiarize physicians with the clinical manifestations, diagnosis, evaluation, prevention, and management of children with iron deficiency anemia. METHODS: A PubMed search was conducted in February 2023 in Clinical Queries using the key term "iron deficiency anemia". The search strategy included all clinical trials (including open trials, non-randomized controlled trials, and randomized controlled trials), observational studies (including case reports and case series), and reviews (including narrative reviews, clinical guidelines, and meta-analyses) published within the past 10 years. Google, UpToDate, and Wikipedia were also searched to enrich the review. Only papers published in the English literature were included in this review. The information retrieved from the search was used in the compilation of the present article. RESULTS: Iron deficiency anemia is most common among children aged nine months to three years and during adolescence. Iron deficiency anemia can result from increased demand for iron, inadequate iron intake, decreased iron absorption (malabsorption), increased blood loss, and rarely, defective plasma iron transport. Most children with mild iron deficiency anemia are asymptomatic. Pallor is the most frequent presenting feature. In mild to moderate iron deficiency anemia, poor appetite, fatigability, lassitude, lethargy, exercise intolerance, irritability, and dizziness may be seen. In severe iron deficiency anemia, tachycardia, shortness of breath, diaphoresis, and poor capillary refilling may occur. When present in early childhood, especially if severe and prolonged, iron deficiency anemia can result in neurodevelopmental and cognitive deficits, which may not always be fully reversible even with the correction of iron deficiency anemia. A low hemoglobin and a peripheral blood film showing hypochromia, microcytosis, and marked anisocytosis, should arouse suspicion of iron deficiency anemia. A low serum ferritin level may confirm the diagnosis. Oral iron therapy is the first-line treatment for iron deficiency anemia. This can be achieved by oral administration of one of the ferrous preparations, which is the most cost-effective medication for the treatment of iron deficiency anemia. The optimal response can be achieved with a dosage of 3 to 6 mg/kg of elemental iron per day. Parenteral iron therapy or red blood cell transfusion is usually not necessary. CONCLUSION: In spite of a decline in prevalence, iron deficiency anemia remains a common cause of anemia in young children and adolescents, especially in developing countries; hence, its prevention is important. Primary prevention can be achieved by supplementary iron or iron fortification of staple foods. The importance of dietary counseling and nutritional education cannot be overemphasized. Secondary prevention involves screening for, diagnosing, and treating iron deficiency anemia. The American Academy of Pediatrics recommends universal laboratory screening for iron deficiency anemia at approximately one year of age for healthy children. Assessment of risk factors associated with iron deficiency anemia should be performed at this time. Selective laboratory screening should be performed at any age when risk factors for iron deficiency anemia have been identified.