How I treat anemia with red blood cell transfusion and iron.

Severe anemia is commonly treated with red blood cell transfusion. Clinical trials have demonstrated that a restrictive transfusion strategy of 7 to 8 g/dL is as safe as a liberal transfusion strategy of 9 to 10 g/dL in many clinical settings. Evidence is lacking for subgroups of patients, including those with preexisting coronary artery disease, acute myocardial infarction, congestive heart failure, and myelodysplastic neoplasms. We present 3 clinical vignettes that highlight the clinical challenges in caring for patients with coronary artery disease with gastrointestinal bleeding, congestive heart failure, or myelodysplastic neoplasms. We emphasize that transfusion practice should be guided by patient symptoms and preferences in conjunction with the patient's hemoglobin concentration. Along with the transfusion decision, evaluation and management of the etiology of the anemia is essential. Iron-restricted erythropoiesis is a common cause of anemia severe enough to be considered for red blood cell transfusion but diagnosis and management of absolute iron deficiency anemia, the anemia of inflammation with functional iron deficiency, or their combination may be problematic. Intravenous iron therapy is generally the treatment of choice for absolute iron deficiency in patients with complex medical disorders, with or without coexisting functional iron deficiency.

Intravenous iron for heart failure, iron deficiency definitions, and clinical response: the IRONMAN trial.

BACKGROUND AND AIMS: What is the relationship between blood tests for iron deficiency, including anaemia, and the response to intravenous iron in patients with heart failure? METHODS: In the IRONMAN trial, 1137 patients with heart failure, ejection fraction ≤ 45%, and either serum ferritin < 100 µg/L or transferrin saturation (TSAT) < 20% were randomized to intravenous ferric derisomaltose (FDI) or usual care. Relationships were investigated between baseline anaemia severity, ferritin and TSAT, to changes in haemoglobin from baseline to 4 months, Minnesota Living with Heart Failure (MLwHF) score and 6-minute walk distance achieved at 4 months, and clinical events, including heart failure hospitalization (recurrent) or cardiovascular death. RESULTS: The rise in haemoglobin after administering FDI, adjusted for usual care, was greater for lower baseline TSAT (Pinteraction < .0001) and ferritin (Pinteraction = .028) and more severe anaemia (Pinteraction = .014). MLwHF scores at 4 months were somewhat lower (better) with FDI for more anaemic patients (overall Pinteraction = .14; physical Pinteraction = .085; emotional Pinteraction = .043) but were not related to baseline TSAT or ferritin. Blood tests did not predict difference in achieved walking distance for those randomized to FDI compared to control. The absence of anaemia or a TSAT ≥ 20% was associated with lower event rates and little evidence of benefit from FDI. More severe anaemia or TSAT < 20%, especially when ferritin was ≥100 µg/L, was associated with higher event rates and greater absolute reductions in events with FDI, albeit not statistically significant. CONCLUSIONS: This hypothesis-generating analysis suggests that anaemia or TSAT < 20% with ferritin > 100 µg/L might identify patients with heart failure who obtain greater benefit from intravenous iron. This interpretation requires confirmation.

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial.

BACKGROUND: Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. METHODS: In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. FINDINGS: Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference -3·1 g [-75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34). INTERPRETATION: In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight. FUNDING: Bill & Melinda Gates Foundation (INV-010612).

The role of iron in chronic inflammatory diseases: from mechanisms to treatment options in anemia of inflammation.

Anemia of inflammation (AI) is a highly prevalent comorbidity in patients affected by chronic inflammatory disorders, such as chronic kidney disease, inflammatory bowel disease, or cancer, that negatively affect disease outcome and quality of life. The pathophysiology of AI is multifactorial, with inflammatory hypoferremia and iron-restricted erythropoiesis playing a major role in the context of disease-specific factors. Here, we review the recent progress in our understanding of the molecular mechanisms contributing to iron dysregulation in AI, the impact of hypoferremia and anemia on the course of the underlying disease, and (novel) therapeutic strategies applied to treat AI.

The oral ferroportin inhibitor vamifeport improves hemodynamics in a mouse model of sickle cell disease.

Sickle cell disease (SCD) is an inherited hemolytic anemia caused by a single point mutation in the ß-globin gene of hemoglobin that leads to synthesis of sickle hemoglobin (HbS) in red blood cells (RBCs). HbS polymerizes in hypoxic conditions, leading to intravascular hemolysis, release of free hemoglobin and heme, and increased adhesion of blood cells to the endothelial vasculature, which causes painful vaso-occlusion and organ damage. HbS polymerization kinetics are strongly dependent on the intracellular HbS concentration; a relatively small reduction in cellular HbS concentration may prevent HbS polymerization and its sequelae. We hypothesized that iron restriction via blocking ferroportin, the unique iron transporter in mammals, might reduce HbS concentration in RBCs, thereby decreasing hemolysis, improving blood flow, and preventing vaso-occlusive events. Indeed, vamifeport (also known as VIT-2763), a clinical-stage oral ferroportin inhibitor, reduced hemolysis markers in the Townes model of SCD. The RBC indices of vamifeport-treated male and female Townes mice exhibited changes attributable to iron-restricted erythropoiesis: decreased corpuscular hemoglobin concentration mean and mean corpuscular volume, as well as increased hypochromic and microcytic RBC fractions. Furthermore, vamifeport reduced plasma soluble VCAM-1 concentrations, which suggests lowered vascular inflammation. Accordingly, intravital video microscopy of fluorescently labeled blood cells in the microvasculature of Townes mice treated with vamifeport revealed diminished adhesion to the endothelium and improved hemodynamics. These preclinical data provide a strong proof-of-concept for vamifeport in the Townes model of SCD and support further development of this compound as a potential novel therapy in SCD.

Intravenous iron in patients with iron deficiency and heart failure: a review of modern evidence.

PURPOSE OF REVIEW: Iron deficiency is common in patients with heart failure, affecting up to half of ambulatory patients and an even greater percentage of patients admitted for acute decompensation. Iron deficiency in this population is also associated with poor outcomes, including worse quality of life in addition to increased hospitalizations for heart failure and mortality. Evidence suggests that patients with iron deficiency in heart failure may benefit from repletion with IV iron. RECENT FINDINGS: In this review, we outline the etiology and pathophysiology of iron deficiency in heart failure as well as various iron formulations available. We discuss evidence for intravenous iron repletion with a particular focus on recent studies that have evaluated its effects on hospitalizations and mortality. Finally, we discuss areas of uncertainty and future study and provide practical guidance for iron repletion. SUMMARY: In summary, there is overwhelming evidence that intravenous iron repletion in patients with iron deficiency in heart failure is both beneficial and safe. However, further evidence is needed to better identify which patients would most benefit from iron repletion as well as the ideal repletion strategy.

Anemia and Iron Supplementation in Relation to Viral Load and Mortality among 70,442 People Living with Human Immunodeficiency Virus in Tanzania.

BACKGROUND: Anemia may be associated with poor clinical outcomes among people living with human immunodeficiency virus (HIV) (PLHIV) despite highly active antiretroviral therapy (HAART). There are concerns that iron supplementation may be unsafe to prevent and treat anemia among PLHIV. OBJECTIVE: The objective of the study was to evaluate the associations of anemia and iron supplementation with mortality and viral load among PLHIV in Tanzania. METHODS: We analyzed data from a cohort of 70,442 nonpregnant adult PLHIV in Tanzania conducted between 2015 and 2019. Regression models evaluated the relationships between anemia severity and iron supplement use with mortality and unsuppressed HIV-1 viral load among all participants and stratified by whether participants were initiating or continuing HAART. RESULTS: Anemia was associated with an increased risk of mortality and unsuppressed viral load for participants who initiated or continued HAART. Iron supplement use was associated with reduced mortality risk but also had a greater risk of an unsuppressed viral load among participants continuing HAART. There was no association of iron supplement use with mortality, and unsuppressed viral load among PLHIV that were initiating HAART. There was a stronger negative association between iron supplement use and the risk of having an unsuppressed viral load among participants with stage III/IV disease compared with stage I/II disease. CONCLUSIONS: Anemia is associated with increased risk of mortality and unsuppressed viral load, but the benefits and safety of iron supplements appear to differ for those initiating compared with continuing ART as well as by HIV disease severity.

LINE-1 global DNA methylation, iron homeostasis genes, sex and age in sudden sensorineural hearing loss (SSNHL).

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is an abrupt loss of hearing, still idiopathic in most of cases. Several mechanisms have been proposed including genetic and epigenetic interrelationships also considering iron homeostasis genes, ferroptosis and cellular stressors such as iron excess and dysfunctional mitochondrial superoxide dismutase activity. RESULTS: We investigated 206 SSNHL patients and 420 healthy controls for the following genetic variants in the iron pathway: SLC40A1 - 8CG (ferroportin; FPN1), HAMP - 582AG (hepcidin; HEPC), HFE C282Y and H63D (homeostatic iron regulator), TF P570S (transferrin) and SOD2 A16V in the mitochondrial superoxide dismutase-2 gene. Among patients, SLC40A1 - 8GG homozygotes were overrepresented (8.25% vs 2.62%; P = 0.0015) as well SOD2 16VV genotype (32.0% vs 24.3%; P = 0.037) accounting for increased SSNHL risk (OR = 3.34; 1.54-7.29 and OR = 1.47; 1.02-2.12, respectively). Moreover, LINE-1 methylation was inversely related (r2 = 0.042; P = 0.001) with hearing loss score assessed as pure tone average (PTA, dB HL), and the trend was maintained after SLC40A1 - 8CG and HAMP - 582AG genotype stratification (ΔSLC40A1 = + 8.99 dB HL and ΔHAMP = - 6.07 dB HL). In multivariate investigations, principal component analysis (PCA) yielded PC1 (PTA, age, LINE-1, HAMP, SLC40A1) and PC2 (sex, HFEC282Y, SOD2, HAMP) among the five generated PCs, and logistic regression analysis ascribed to PC1 an inverse association with moderate/severe/profound HL (OR = 0.60; 0.42-0.86; P = 0.0006) and with severe/profound HL (OR = 0.52; 0.35-0.76; P = 0.001). CONCLUSION: Recognizing genetic and epigenetic biomarkers and their mutual interactions in SSNHL is of great value and can help pharmacy science to design by pharmacogenomic data classical or advanced molecules, such as epidrugs, to target new pathways for a better prognosis and treatment of SSNHL.

The fatigue after infusion or transfusion pilot trial and feasibility study: A three-armed randomized pilot trial of intravenous iron and blood transfusion for the treatment of postpartum anemia.

BACKGROUND: Evidence for the management of moderate-to-severe postpartum anemia is limited. A randomized trial is needed; recruitment may be challenging. STUDY DESIGN AND METHODS: Randomized pilot trial with feasibility surveys. INCLUSION: hemoglobin 65-79 g/L, ≤7 days of birth, hemodynamically stable. EXCLUSION: ongoing heavy bleeding; already received, or contraindication to intravenous (IV)-iron or red blood cell transfusion (RBC-T). Intervention/control: IV-iron; RBC-T; or IV-iron and RBC-T. PRIMARY OUTCOME: number of recruits; proportion of those approached; proportion considered potentially eligible. SECONDARY OUTCOMES: fatigue, depression, baby-feeding, and hemoglobin at 1, 6 and 12 weeks; ferritin at 6 and 12 weeks. Surveys explored attitudes to trial participation. RESULTS: Over 16 weeks and three sites, 26/34 (76%) women approached consented to trial participation, including eight (31%) Maori women. Of those potentially eligible, 26/167 (15.6%) consented to participate. Key participation enablers were altruism and study relevance. For clinicians and stakeholders the availability of research assistance was the key barrier/enabler. Between-group rates of fatigue and depression were similar. Although underpowered to address secondary outcomes, IV-iron and RBC-T compared with RBC-T were associated with higher hemoglobin concentrations at 6 (mean difference [MD] 11.7 g/L, 95% confidence interval [CI] 2.7-20.7) and 12 (MD 12.8 g/L, 95% CI 1.5-24.2) weeks, and higher ferritin concentrations at 6 weeks (MD 136.8 mcg/L, 95% CI 76.6-196.9). DISCUSSION: Willingness to participate supports feasibility for a future trial assessing the effectiveness of IV-iron and RBC-T for postpartum anemia. Dedicated research assistance will be critical to the success of an appropriately powered trial including women-centered outcomes.

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.

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.

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.

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.

Clinical effectiveness of ferric carboxymaltose (iv) versus iron sucrose (iv) in treatment of iron deficiency anaemia in pregnancy: A systematic review and meta-analysis.

BACKGROUND OBJECTIVES: Iron deficiency anaemia (IDA) during pregnancy is treated with oral and parenteral iron. The objective of this review was to compare the clinical effectiveness, safety, pregnancy and neonatal outcomes of intravenous (iv) ferric carboxymaltose (FCM) and iv iron sucrose (IS) in treating IDA in pregnancy. METHODS: The Department of Health Research funded this study. PubMed, Cochrane Library, EMBASE and Scopus were searched to include studies published till November 2022. The protocol was registered in PROSPERO (CRD42022306092). Pregnant women (15-49 yr) in second and third trimesters, diagnosed with moderate-to-severe iron deficiency anaemia, treated with either of the drugs were included. The included studies were critically assessed using appropriate tools. We conducted a qualitative synthesis of the studies and meta-analysis for improvement in haematological parameters and incidence of adverse events. RESULTS: A total of 18 studies were included. The risk of bias was low to moderate. A rise in haemoglobin up to four weeks was higher with FCM than IS by 0.57 (0.24, 0.9) g/dl. Intravenous FCM is associated with fewer adverse events than IS [pooled odds ratio: 0.5 (0.32, 0.79)]. The included studies had limited evidence on pregnancy and neonatal outcomes after iv iron treatment. INTERPRETATION CONCLUSIONS: Intravenous FCM is effective and safer than intravenous IS in terms of haematological parameters, in treating IDA in pregnancy. Further research is required on the effects of iv FCM and iv IS on the pregnancy and neonatal outcomes when used for treating IDA in pregnancy.

GATA3 mediates doxorubicin resistance by inhibiting CYB5R2-catalyzed iron reduction in breast cancer cells.

AIMS: Neoadjuvant chemotherapy (NAC) is the primary preoperative therapy for breast cancer. The luminal subtype of breast cancer shows less NAC response than the basal subtype, with an inefficient NAC treatment effect. Understanding of the molecular and cellular mechanisms responsible for this chemoresistance is an important issue when determining optimal treatment. METHODS: Doxorubicin-induced apoptosis and ferroptosis was investigated using cytotoxicity, western blotting, and flow cytometry assays. The role of GATA3 in modulating doxorubicin-induced cell death was investigated both in vitro and in vivo. RNA-seq, qPCR, ChIP, and luciferase assay and association analyses were performed to investigate the regulation of CYB5R2 by GATA3. The function of GATA3 and CYB5R2 in regulating doxorubicin-induced ferroptosis was evaluated with iron, ROS, and lipid peroxidation detection assays. Immunohistochemistry was performed for results validation. RESULTS: Doxorubicin-induced basal breast cancer cell death is dependent on iron-mediated ferroptosis. Overexpression of the luminal signature transcriptional factor GATA3 mediates doxorubicin resistance. GATA3 promotes cell viability by decreasing ferroptosis-related gene CYB5R2 expression and by maintaining iron homeostasis. Analyzing data from the public and our cohorts demonstrates that GATA3 and CYB5R2 are associated with NAC response. CONCLUSIONS: GATA3 promotes doxorubicin resistance by inhibiting CYB5R2-mediated iron metabolism and ferroptosis. Therefore, patients with breast cancer who display high GATA3 expression do not benefit from doxorubicin-based NAC regimens.

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.

Potential anticancer effect of free and nanoformulated Deferasirox for breast cancer treatment: in-vitro and in-vivo evaluation.

BACKGROUND: Breast cancer (BC) stands as the second-leading cause of mortality among women worldwide. Many chemotherapeutic treatments for BC come with significant adverse effects. Additionally, BC is recognized as one of the most resistant forms of malignancy to treatment. Consequently, there exists a critical need for innovative therapeutic agents that are both highly effective and exhibit reduced toxicity and side effects for patients. Deferasirox (DFX), an iron-chelating drug approved by the FDA for oral use, emerges as a promising contender in the fight against BC proliferation. DFX, primarily administered orally, is utilized to address chronic iron excess resulting from blood transfusions, and it is the inaugural treatment for chronic iron overload syndrome. However, DFX encounters limitations due to its poor water solubility. AIM: This study aimed at incorporating DFX into lipid nanocapsules (DFX-LNCs) followed by investigating the anticancer effect of the DFX nanoform as compared to free DFX in-vitro and on an orthotopic BC mouse model in-vivo. METHODS: The DFX-LNCs was prepared and imaged using TEM and also characterized in terms of particle size (PS), zeta potential (ZP), and polydispersity index (PDI) using DLS. Moreover, drug release, cytotoxicity, and anticancer effect were assessed in-vitro, and in-vivo. RESULTS: The results revealed that DFX-LNCs are more cytotoxic than free DFX with IC50 of 4.417 µg/ml and 16.114 µg/ml, respectively, while the plain LNCs didn't show any cytotoxic effect on the 4T1 cell line (IC50 = 122.797 µg/ml). Besides, the apoptotic effect of DFX-LNCs was more pronounced than that of free DFX, as evidenced by Annexin V/PI staining, increased BAX expression, and decreased expression of BcL-2. Moreover, DFX-LNCs showed a superior antitumor effect in-vivo with potent antioxidant and anti-proliferative effects. CONCLUSION: The newly developed DFX nanoform demonstrated a high potential as a promising therapeutic agent for BC treatment.

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.

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.

Micronutrient supplementation practices in relation to the World Health Organisation 2013 guidelines on management of severe acute malnutrition.

In 2013, the World Health Organisation (WHO) updated the recommendations for micronutrient deficiency correction in hospitalised under-5 children with complicated severe acute malnutrition (SAM). This study aimed to describe the micronutrient deficiency correction practices in relation to WHO 2013 recommendations. Data from medical records of under-5 children admitted for SAM management at two hospitals in South Africa and three tertiary hospitals in Ghana were extracted. Micronutrient correction practices were compared to the WHO 2013 recommendations by considering the dosage, timing of micronutrient supplementation (vitamin A, iron and folic acid) and therapeutic feeds administered. In total, 723 medical records were included. Nearly half (48.3%) of the children received at least one of the studied micronutrients as a supplement. Vitamin A was supplemented in 27.4% of the children, while iron and folic acid were supplemented in 9.5% and 34.9%, respectively. Among the children who received vitamin A, 60.1% received the first dose on Day 1 of admission. Also, 46.4% of the iron-supplemented children received iron within the first week of admission. Vitamin A, iron and folic acid were administered within the dose range of 100,000-180,000 IU, 3.1-7.7 mg per kg per day, and 3-5 mg per day, respectively. Additionally, 71.7% of the children reportedly received therapeutic feeds that met WHO recommendations. The micronutrient deficiency correction practices regarding dose and timing differed from the 2013 WHO guidelines. Qualitative studies investigating the reasons for the disparities are recommended.