Search Results (652)

Background: Iron-refractory iron deficiency anemia (IRIDA) is a rare hereditary disorder caused by pathogenic variants in TMPRSS6, characterized by microcytic anemia, low circulating iron levels, and inappropriately high hepcidin levels. Although IRIDA is typically an autosomal recessive disorder, some individuals with a monoallelic pathogenic exonic TMPRSS6 variant exhibit the phenotype, suggesting additional contributing factors. The mechanisms underlying monoallelic IRIDA remain unclear, complicating diagnosis. This study aimed to investigate the potential role of non-coding TMPRSS6 variants and polygenic inheritance in monoallelic IRIDA. Methods: We performed full-gene sequencing of TMPRSS6 in a cohort of 27 subjects, including 6 families (7 symptomatic monoallelic, 7 asymptomatic monoallelic, and 4 wild-type subjects) and 9 isolated symptomatic monoallelic subjects. Whole-exome sequencing of other iron-regulating genes was conducted to evaluate polygenic inheritance. Non-coding variants were assessed for inheritance patterns using family segregation analysis, when available, and for pathogenic potential using in silico prediction tools. Results: Sequencing identified 219 non-coding variants, of which 31 (14 trans-inherited and 17 with unknown inheritance) were exclusive to symptomatic subjects. Two trans-inherited variants (rs80140288 (c.229+945C>T) and rs146953827 (c.230-938_230-937del)) were predicted to affect splicing, while two additional variants (rs78987624 (c.-7001G>A) and rs117575523 (c.*503C>G)) were located in regulatory regions (with unknown inheritance). Whole-exome sequencing did not support polygenic involving other iron-regulating genes. Conclusions: This study highlights four candidate non-coding variants that may contribute to IRIDA expression in monoallelic subjects, offering new insights into its genetic basis. Functional validation is required to confirm their role in disease pathogenesis, refine genotype-phenotype correlations, and improve diagnostic accuracy in monoallelic IRIDA. Full article

Background: Nutritional deficiency anemias—including iron, vitamin B12, and folate deficiencies—are common worldwide and are increasingly recognized as potential contributors to venous thromboembolism (VTE). Mechanistic and epidemiologic data suggest that anemia may promote thrombosis through hypoxia, endothelial activation, reactive thrombocytosis, and hyperhomocysteinemia. However, a focused synthesis of clinical and genetic evidence specifically linking nutritional deficiency anemia to VTE has been lacking. Methods: We conducted a systematic search of PubMed and the Cochrane Library from inception to 30 September 2025 to identify studies assessing nutritional deficiency anemia in relation to VTE outcomes. Eligible studies included observational designs, case reports, case series, and Mendelian randomization (MR) analyses. Quality assessment followed the Newcastle–Ottawa Scale (NOS), Joanna Briggs Institute (JBI) checklists, and ROB-MR. The review was registered in PROSPERO (CRD420251235479). Results: Seven studies met the inclusion criteria. Observational analytical studies consistently showed that anemia was associated with adverse VTE-related outcomes. Lower hemoglobin predicted higher short-term mortality in acute pulmonary embolism (HR 1.16 per 1 g/dL decrease), increased symptomatic VTE among hospitalized patients (RR 1.94), and greater long-term bleeding and mortality risk in VTE cohorts (HRs 1.41–2.89). Iron-deficiency anemia increased the odds of VTE in population-based data (OR 1.43), and case reports described unprovoked DVT in young adults with moderate to severe anemia. The MR study indicated a potential causal association between anemia traits and thrombosis at unusual anatomical sites (OR 1.446). No study demonstrated a significant association with recurrent VTE. Most analytical studies were rated as good–high quality. Conclusion: Across multiple study designs, anemia—particularly iron-deficiency anemia and low baseline hemoglobin—appears to be an underrecognized factor associated with elevated VTE risk and adverse VTE-related outcomes. However, direct evidence for vitamin B12- and folate-deficiency anemia remains limited, and further well-designed prospective studies are required to confirm causality and clarify the contribution of specific nutritional deficiency subtypes, as well as to support integration of anemia assessment into VTE risk models. Full article

Background: Iron-deficient anemia (IDA) in pregnant women is a significant health issue globally. Oral iron supplementation is the primary treatment for IDA during pregnancy. For women who do not respond to or cannot tolerate oral iron treatment, intravenous (IV) iron preparations may offer a viable therapeutic option in the third trimester of pregnancy. Ferric carboxymaltose (FCM; Ferinject^®) is an IV iron preparation that allows rapid administration of high single doses of iron with a favorable safety profile. This study evaluated the potential impact of FCM therapy on fetal well-being by recording cardiotocography (CTG) before, during, and after iron infusions. Materials and Methods: We examined 105 women with IDA in the third trimester of pregnancy. During the initial evaluation, each patient was assessed for complete blood count, iron metabolism, B12, folates, hemoglobinopathies, CRP, kidney and liver function, and glucose levels. Each subject received intravenous ferric carboxymaltose (FCM), 500 mg. The study focused on the maternal and fetal safety of FCM infusion. The primary endpoint for maternal safety was the observation of adverse effects of iron infusion. For fetal safety, the primary endpoint was the assessment of CTG. Results: We considered 105 women, comprising 101 singleton and 4 twin pregnancies. The median hemoglobin (Hb) at initial observation was 95 g/L and 117 g/L post-therapy. Regarding maternal safety, side effects were observed during or after FCM infusion in four subjects; three cases involved local symptoms, while one case included nausea and skin rash. Concerning fetal safety, 100% of the cardiotocography records were deemed “normal” using the Dawes–Redman criteria. Conclusions: In conclusion, FCM proved effective in treating anemia in this clinically complex population of pregnant women in the third trimester and appeared safe in this cohort, though larger prospective studies are warranted. Full article

Background/Objectives: Iron deficiency (ID) is the most common nutritional disorder in childhood worldwide. It has profound consequences for growth, neurodevelopment, behaviour, and overall health. Despite the long-standing efficacy of oral ferrous salts, their poor gastrointestinal tolerability and adherence challenges have spurred the development of alternative formulations and innovative dosing strategies. Methods: We conducted a narrative review of national and international guidelines, pediatric randomized controlled trials, observational and cohort studies, cost-effectiveness analyses, diagnostic method papers, and reviews, with emphasis on diagnostic innovations, therapeutic outcomes, tolerability, and formulation-specific efficacy. Results: Ferrous salts remain the gold standard for efficacy, low cost, and guideline endorsement, but up to 40% of children experience GI intolerance. Therefore, a lower dosage of ferrous salts has been proposed for IDA as still being an efficacious and better-tolerated schedule. Also, alternate-day dosing improves absorption and tolerability and is supported by a recent pediatric RCT. Newer formulations—ferric polymaltose, ferrous bisglycinate, co-processed bisglycinate with alginate (Feralgine™), and vesicular encapsulated forms such as sucrosomial and liposomal ferric pyrophosphate—showed improved tolerability and palatability, supporting adherence with hematologic outcomes comparable to ferrous salts, particularly in children with intolerance, malabsorption, or inflammatory comorbidities. Intravenous iron is effective and safe with modern preparations and is reserved for severe anemia, malabsorption, or oral therapy failure. Conclusions: Oral ferrous salts should remain the first-line therapy in pediatric ID/IDA. Future pediatric trials should prioritize head-to-head comparisons of formulations, hepcidin-guided dosing, and patient-centred outcomes, including neurocognitive trajectories and quality of life. Full article

Wheat (Triticum aestivum L.) is one of the most important staple crops in the world. Iron (Fe) plays a vital role in the growth and development of wheat as an essential nutrient. Meanwhile, Fe is closely associated with human health, as Fe deficiency anemia can cause fatigue, weakness, heart problems, and so on. In this study, quantitative trait loci (QTLs) for grain Fe content (GFeC) were detected in two populations: a recombinant inbred line (RIL) population with 175 lines derived from a cross between Avocet and Huites (AH population) genotyped with diversity array technology (DArT) and a natural population of 243 varieties (CH population) genotyped by using the 660K single-nucleotide polymorphism (SNP). Three stable QTLs (QGFe.haust-AH-5B, QGFe.haust-AH-6A, and QGFe.haust-AH-7A.2) were identified through QTL mapping with phenotypic variations of 11.55–13.63%, 3.58–9.89%, and 4.81–11.12% in the AH population in four environments. Genetic effects of QGFe.haust-AH-5B, QGFe.haust-AH-6A, and QGFe.haust-AH-7A.2 were shown to significantly increase GFeC by 8.11%, 14.05%, and 5.25%, respectively. One hundred and thirty-three significant SNPs were identified (p < 0.001) through a genome-wide association study (GWAS) for GFeC on chromosomes 1B, 2B, 3A, 3B, 5D, and 7A with phenotypic variations of 5.26–9.88% in the CH population. A novel locus was co-located within the physical interval 689.86 Mb-690.01 Mb in five environments through QTL mapping and GWAS, with one high-confidence gene, TraesCS7A02G499500, which was temporarily designated as TaqFe-7A, involved in GFeC regulation. A Kompetitive allele-specific PCR, KAFe-7A-2, was developed, which was validated in 181 natural populations. Genetic effect analysis revealed that favorable haplotype AA significantly increased GFeC by 4.64% compared to an unfavorable haplotype (p < 0.05). Therefore, this study provides the theoretical basis for cloning the GFeC gene and nutritional fortification breeding. Full article

Background: Preoperative anemia is common among patients undergoing arthroplasty and is associated with increased transfusion requirements and worse outcomes. Current perioperative pathways rely on iron studies to guide intravenous iron supplementation, but systemic inflammation triggered by surgery profoundly alters iron markers, risking misclassification of iron deficiency. This study evaluated whether adjusting iron indices for inflammatory markers improves diagnostic accuracy after total hip arthroplasty (THA). Methods: In this prospective cohort study, 20 patients undergoing elective primary THA at a single center were enrolled. Patients with preoperative inflammation were excluded. Serum iron, transferrin, transferrin saturation (TSAT), CRP, and albumin were measured preoperatively and on postoperative days (PODs) 1, 2, 3, and 90. Serum iron was adjusted for systemic inflammation using a validated regression equation incorporating CRP and albumin, and adjusted TSAT was calculated accordingly. Absolute iron deficiency was defined as serum iron < 10 µmol/L, and functional iron deficiency was defined as TSAT < 20%. Comparisons were made using Wilcoxon’s signed-rank test and ANOVA. Results: In the 20 included patients, a pronounced systemic inflammatory response was observed, with CRP peaking on POD 2 (median, 162 mg/L) and albumin falling to 32 g/L on POD 1 (both p < 0.001). Unadjusted serum iron and TSAT fell sharply, with nearly all patients classified as iron-deficient in the first three postoperative days. Adjustment for CRP and albumin significantly attenuated these declines: on POD 2, median iron was 8.2 µmol/L adjusted versus 2.0 µmol/L unadjusted (p < 0.001), and TSAT was 19% versus 4% (p < 0.001). Misclassification of iron deficiency fell by 40–50% with adjustment, and by POD 90, adjusted indices approximated baseline values. Conclusions: Systemic inflammation after THA markedly suppresses iron indices, leading to widespread misclassification of iron deficiency. Adjustment for CRP and albumin reduces this misclassification and provides a more accurate assessment of perioperative iron status. These findings complement existing evidence supporting intravenous iron supplementation by highlighting a diagnostic refinement that could improve patient selection for therapy. Full article

Background/Objectives: Micronutrient deficiencies during infancy remain a major public health concern, particularly in developing countries. Although exclusive breastfeeding is the optimal source of nutrition for infants up to six months of age, limited studies have simultaneously evaluated multiple micronutrient statuses in this population. This study aimed to assess the levels of vitamin D, iron, and other micronutrients—including vitamins A, E, B12, folic acid, zinc, and copper—in exclusively breastfed infants. Methods: This cross-sectional study was conducted between 2022 and 2024 at a university well-child clinic in İzmir, Turkey. A total of 132 healthy, exclusively breastfed six-month-old infants were included. Blood samples were analyzed for hemogram, serum iron, ferritin, 25(OH)D, vitamins A, E, B12, folic acid, zinc, and copper. Sociodemographic data and supplementation practices were recorded. Deficiency cut-offs were defined according to WHO and national guidelines. Results: Among the infants, 40.2% had iron deficiency or anemia, and 14.4% had vitamin D deficiency. Vitamin B12, A, E, zinc, and copper deficiencies were identified in 29.5%, 2.4%, 4%, 7.4%, and 6.6% of infants, respectively. Regular vitamin D and iron supplementation were significantly associated with lower deficiency rates (p < 0.05). Maternal education level, dressing style, and smoking status were significantly related to infant vitamin D status. Conclusions: Despite national supplementation programs, iron and vitamin D deficiencies remain common in exclusively breastfed infants. Routine and regular supplementation should be emphasized, and subclinical deficiencies—particularly vitamin B12—should be considered. Broader studies evaluating maternal nutritional factors and socioeconomic determinants are warranted to guide preventive strategies. Full article

Background: Iron deficiency anemia is a recognized pregnancy risk, but excessive iron may also have adverse effects. Few studies, particularly in Asian populations, have examined elevated maternal ferritin in relation to birth outcomes. Objectives: To investigate the dose–response relationships between maternal serum ferritin concentrations in late pregnancy and birth outcomes, including preterm birth, small for gestational age (SGA), and placental characteristics. Methods: A retrospective study of 362 mother–infant pairs were analyzed. Maternal serum ferritin levels measured at 30–34 weeks’ gestation were divided into quintiles, using 30.1–43.0 µg/L as the reference. Logistic and linear regression models were applied to examine associations with preterm birth, SGA, and placental indices. Results: Preterm birth rates ranged 7.3–18.8% across ferritin quintiles, but no significant association was observed. In contrast, SGA prevalence increased from 20.8% to 47.2% (p-trend = 0.001). Women in the highest ferritin quintile had 3.31-fold higher adjusted odds of SGA (95% CI: 1.51–7.28, p = 0.003). Each SD increase in ferritin corresponded to 31% higher odds of SGA (OR = 1.31, 95% CI: 1.01–1.71). Elevated ferritin (>43.0 µg/L) was also associated with reduced placental weight (<415 g) (adjusted OR = 3.02, 95% CI: 1.61–5.69, p = 0.001). Conclusions: Increasing maternal ferritin levels in the third trimester were associated with a dose-dependent rise in SGA risk and reduced placental weight. These findings suggest that excessive iron status may adversely influence placental function and fetal growth, underscoring the need for individualized nutrition management during pregnancy. Full article

Iron deficiency anemia remains a major public health concern in Brazil, particularly among children, pregnant women, and women of childbearing age. This scoping review aimed to map the trend line of public policies on iron supplementation and food fortification implemented between 1977 and 2025. The review followed PRISMA-ScR guidelines and the Joanna Briggs Institute methodology, and included searches in PubMed/MEDLINE, Scopus, Web of Science, Embase, Google Scholar, and official government documents. Three main strategies were identified: iron supplementation, mandatory food fortification, and nutrition education. Key milestones included the National Iron Supplementation Program, the 2002 ANVISA Resolution (RDC No. 344/2002) mandating wheat and corn flour fortification, and the launch of the NutriSUS program in 2014. Despite important normative and programmatic advances, persistent critical issues remain, including low adherence, inadequate monitoring, data discontinuity, and bureaucratic barriers. Strengthening intergovernmental coordination, improving information systems, and adopting more bioavailable iron compounds are essential to increase the effectiveness of public policies aimed at preventing and controlling iron deficiency anemia in Brazil. Full article

Efficient oxygen transport and accurate anemia diagnostics remain significant medical challenges, as current therapies suffer from stability limitations, immunogenic risks, and inadequate sensitivity. Cucurbiturils (CB[n]), a family of pumpkin-shaped supramolecular macrocycles, present promising solutions due to their rigid architecture, hydrophobic cavities, and strong host–guest binding properties. Functional derivatives such as perhydroxy-cucurbit[5]uril can reversibly bind dioxygen under physiological conditions, highlighting their potential as synthetic hemoglobin substitutes. Additionally, cucurbituril-based probes for Fe³⁺ and folate enable sensitive and selective detection of iron- and folate-deficiency anemia. Biocompatibility assessments in vitro and in vivo indicate low systemic toxicity and acceptable hemocompatibility for homologues such as CB[6], CB[7], and CB[8], though apoptosis, myotoxicity, or cardiotoxicity may occur at elevated concentrations. These data emphasize the need for thorough toxicological evaluation but also demonstrate that cucurbiturils provide a versatile platform for oxygen transport, diagnostic applications, and drug-delivery strategies in anemia management. While their translation to clinical practice is still at an early stage, the structural tunability, stability, and encouraging safety profile of CB[n] macrocycles offer a strong basis for continued biomedical development. Full article

Iron deficiency anemia continues to pose a significant global health burden, necessitating the development of improved therapeutic delivery systems. This study investigates novel composite materials composed of organosilicon hydrogels and cross-linked sulfobutyl ether beta-cyclodextrin (SBECD) nanoparticles for the oral delivery of iron compounds. Two types of cross-linked SBECD nanoparticles were synthesized using 1,6-hexamethylene diisocyanate. These nanoparticles were characterized by DLS, NTA, and FTIR and possess size around 200–300 nm and negative zeta-potential around −35 mV with molecular weight 150–200 kDa. Various hydrogel matrices, including plain PMSSO hydrogels and modified versions with amino groups or silicate cross-links, are also described. The hydrogels were evaluated for their iron sorption capacity (up to 44% loading efficiency) and release kinetics for 3 h. The results demonstrate that cross-linked SBECD nanoparticles significantly enhance iron sorption and provide sustained release under simulated physiological conditions. Mathematical modeling indicated that the Higuchi model best describes the iron release kinetics. The findings suggest that the proposed composite materials hold considerable promise for the treatment of iron deficiency anemia, offering an innovative approach to enhance therapeutic efficacy and minimize adverse effects. Full article

Objectives: The aim was to evaluate the clinical features, management and 1-year outcomes in patients with heart failure (HF) and advanced chronic kidney disease (CKD) who were followed in specialized HF units in Spain. Methods: Data from the registry of the SEC-Excellent-HF quality program of the Spanish Society of Cardiology were analyzed. This registry included 1567 patients between 2019 and 2022 followed by 45 specialized HF units. Clinical features, treatment and 1-year rate of events (death and HF hospitalizations) were compared between the groups of advanced CKD (glomerular filtration rate <30 mL/minute/m²) and GFR ≥ 30 mL/min/m². Results: 11.1% of patients had a GFR < 30 and 88.9% ≥ 30 mL/min/m². The median LVEF was similar in groups with GFR < 30 and ≥30 mL/min/m²: 42% (IQR 30–58) versus 38% (IQR 29–54). Advanced CKD patients were older, had more severe HF (previous HF admissions in the last year, worse NYHA functional class and longer evolution time) and had higher prevalence of ischemic heart disease, diabetes mellitus, systemic hypertension, iron deficiency, anemia and hyponatremia. All drugs for HF, except for diuretics and potassium binders, were used in a lower proportion in patients with GFR < 30 mL/min/m² (p < 0.001). One-year overall mortality (49.2 versus 13.7/100 patients-year; p < 0.001) and one-year HF hospitalizations rate (83.2 versus 30.7/100 patients-year; p < 0.001) were higher in the group of advanced CKD. Conclusions: In our study, patients with advanced CKD had different clinical characteristics, received indicated treatment in a lower proportion and had higher 1-year rates of death and HF admissions. Full article

Background: Disturbed iron metabolism has been described in chronic diseases with pro-inflammatory/immune activation. This study aimed to characterize iron status in patients with atopic dermatitis (AD) and to examine its relationship with disease severity and quality of life. Methods: We prospectively enrolled 86 adult patients with moderate-to-severe AD. Clinical assessments included the Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), and the Dermatology Life Quality Index (DLQI). Blood samples were collected for hematologic parameters and iron-related biomarkers, including serum iron, ferritin, transferrin, transferrin saturation (Tsat), soluble transferrin receptor (sTfR), and hepcidin. Associations between iron markers and clinical outcomes were evaluated using beta regression models with variable selection and stability analyses. Results: Abnormalities in circulating iron biomarkers indicating iron deficiency were prevalent in patients with AD: 45% of patients had low Tsat (<20%), 37% low ferritin, and 26% reduced serum iron, despite largely normal hemoglobin. Patients with pro-inflammatory activation (as evidenced by elevated high-sensitivity C-reactive protein (hsCRP) above 5 mg/L) displayed a pattern characterized by lower iron, Tsat and higher sTfR levels. In multivariable analyses, lower serum iron remained associated with worse DLQI scores, while higher transferrin was associated with greater disease severity (EASI, SCORAD). Conclusions: Iron deficiency without anemia was a common feature of moderate-to-severe AD and was associated with higher clinical burden. Dysregulated systemic iron homeostasis was associated with impaired quality of life and increased disease severity. Full article

Background/Objectives: Children with stunting are at risk of immune function disruption and micronutrient deficiencies, leading to nutritional anemia and susceptibility to infection. This study determined the prevalence and etiology of anemia in children under five with stunting and tuberculosis (TB) and analyzed the associated factors. Methods: A cross-sectional study was conducted among children under five with stunting from 30 May to 13 June 2022. Participants were selected via the proportionate stratified random sampling of 74 community health centers in Bandung City, Indonesia. An anthropometric measurement was performed to determine stunting and conduct TB diagnosis, and hematology tests were performed to elaborate the anemia profiles. Results: In total, 138 participants were included, among which 80 (58.0%) had TB and 57 (41.3%) had anemia, mostly caused by iron deficiency anemia (IDA)—38/57 (66.7%). The coexistence of anemia in children with stunting and TB was present in 33 (23.9%) and it was associated with nutritional status (weight-for-length), p = 0.026. Conclusions: Anemia, as a part of the triple burden among children under five with stunting and TB was highly prevalent, mostly due to IDA; in this study, only nutritional status was associated with the triple burden. Full article

Preoperative anemia and non-anemic iron deficiency are common in cardiac surgery patients. Both are frequently caused by absolute iron deficiency or are associated with chronic diseases and inflammation. Multiple studies have shown an association between preoperative anemia and increased RBC transfusion, prolonged intensive care unit and hospital length of stay, and higher postoperative morbidity and mortality. The impact of preoperative non-anemic iron deficiency on postoperative adverse outcome is less clear, but worsened postoperative outcomes have been suggested. Accordingly, treatment for anemia and iron deficiency is a primary goal in preoperative optimization in cardiac surgery patients. Several guidelines recommend timely supplementation with modern oral iron formulation as first-line intervention, followed by intravenous iron administration in case of patient intolerance or time restriction. In patients with non-pure iron deficiency or in ultra-short treatment strategies, the combined therapy of intravenous iron and erythropoiesis-stimulating agents seems safe and most efficacious to increase red blood mass before surgery. However, the positive effects of preoperative interventions in anemic or iron-deficient patients were mostly limited to reduced transfusion of red blood cells, whereas lower morbidity and mortality were shown in limited studies only. It is also important to note that allogeneic blood products are a limited resource, and preoperative oral iron supplementation showed the best cost-effectiveness. Full article