Unlocking the Power of Human Ferritin: Enhanced Drug Delivery of Aurothiomalate in A2780 Ovarian Cancer Cells.

Aurothiomalate (AuTM) is an FDA-approved antiarthritic gold drug with unique anticancer properties. To enhance its anticancer activity, we prepared a bioconjugate with human apoferritin (HuHf) by attaching some AuTM moieties to surface protein residues. The reaction of apoferritin with excess AuTM yielded a single adduct, that was characterized by ESI MS and ICP-OES analysis, using three mutant ferritins and trypsinization experiments. The adduct contains ~3 gold atoms per ferritin subunit, arranged in a small cluster bound to Cys90 and Cys102. MD simulations provide a plausible structural model for the cluster. The adduct was evaluated for its pharmacological properties and was found to be significantly more cytotoxic than free AuTM against A2780 cancer cells mainly due to higher gold uptake. NMR-metabolomics showed that AuTM bound to HuHf and free AuTM induced qualitatively similar changes in treated cancer cells, indicating that the effects on cell metabolism are approximately the same, in agreement with independent biochemical experiments. In conclusion, we have demonstrated here that a molecularly precise bioconjugate formed between AuTM and HuHf exhibits anticancer properties far superior to the free drug, while retaining its key mechanistic features. Evidence is provided that human ferritin can serve as an excellent carrier for this metallodrug.

A clinical study evaluating low dose ferrous fumarate vs. standard iron supplements in iron-deficient non-anemic to mild anemic adults.

Our study aims to validate safety and efficacy of Feroglobin capsule compared with different iron supplementations in adult subjects diagnosed with non-anemic to mild anemic iron deficiency and fatigue. Enrolled 302 participants diagnosed with non-anemic to mild anemic iron deficiency and fatigue. Group A (n = 147) received Feroglobin, Group B (n = 146) received standard of care [Haem Up Gems capsules (Ferrous fumarate) or Fericip tablets (Ferrous ascorbate)]. 293 subjects completed the study with follow-up visits on days 30, 60, and 90. Feroglobin treatment significantly increased hemoglobin levels from mean 12.43 g/dl to 13.24 g/dl in 90 days. Ferritin levels improved significantly by 442.87% compared to the standard care's 256.67%. Fatigue scale scores reduced by 47.51%, and all presenting health complaints resolved completely. Gastrointestinal symptoms observed were similar in both the groups. Both groups exhibited moderate treatment adherence. Quality of life improved in pain and general health domains, exhibiting a good tolerability. Adverse events were unrelated to the investigational products. Feroglobin serves as an efficacious therapeutic alternative for improving hemoglobin, ferritin, and reducing fatigue with low doses compared to standard of care. However, longer-term effects of low-dose require further investigations in different target groups.

Dietary diversity and iron deficiency anemia among a cohort of singleton pregnancies: a cross-sectional study.

BACKGROUND: Iron deficiency anemia (IDA) is considered one of the most common medical disorders observed during pregnancy. In low- and middle-income countries (LMICs), anemia and micronutrients deficiencies among pregnant women are associated with low consumption of animal products, monotonous starchy-diets, and seasonal consumption of vegetables and fruits. METHODS: A cross-sectional study was conducted with 198 pregnant mothers aged between 19-45 years who visited the antenatal care clinics in Northern Jordan to document the prevalence of IDA and to describe the associations between dietary diversity, diet quality scores and oral iron supplementation with the pregnant women iron status. Participants were stratified into three groups by gestational age (n = 66 women per group). Gestational age, blood parameters, minimum dietary diversity score (MDD-W), and prime diet quality score for healthy (PDQSHF) and unhealthy foods (PDQSUF) were assessed using 24- hour dietary recall. RESULTS: Prevalence of mild to moderate anemia was 27.8% among pregnant women. Third-trimester pregnant women were most affected. 52.5% have depleted iron stores (ferritin < 15 ng/ml), of them 30.8% have iron deficiency, and 21.7% have IDA. The (M ± SD) of the MDD-W, PDQSHF, and PDQSUF were 4.8 ± 1.6, 12.8 ± 3.9, and 7.2 ± 2.8 respectively. 52.5% achieved the MDD-W, 68% consumed < 4 servings/week of healthy food groups, and 50% consumed > 4 servings/week of unhealthy food groups. Mothers with higher MDD-W and PDQS had higher Hb and serum concentrations. Those taking iron supplements had significantly (p = 0.001) higher means of Hb, serum ferritin, and gestational weight gain. Significant differences were also found between PDQSHF, PDQSUF and the first and third trimester. CONCLUSIONS: Mild to moderate IDA is prevalent among pregnant mothers, especially in the third trimester. However, the prevalence of IDA among Jordanian pregnant women is lower than the global average. A high-quality, diverse diet, combined with oral iron supplementation and food fortification with iron, will help improve iron status, prevent anemia, and reduce its prevalence.

The role of LDH and ferritin levels as biomarkers for corticosteroid dosage in children with refractory Mycoplasma pneumoniae pneumonia.

BACKGROUND: This study explored the relationship between inflammatory markers and glucocorticoid dosage upon admission. METHODS: We conducted a retrospective analysis of 206 patients with refractory Mycoplasma pneumoniae pneumonia (RMPP) admitted to a Children's Hospital from November 2017 to January 2022. Patients were categorized into three groups based on their methylprednisolone dosage: low-dose (≤ 2 mg/kg/d), medium-dose (2-10 mg/kg/d), and high-dose (≥ 10 mg/kg/d). We compared demographic data, clinical manifestations, laboratory findings, and radiological outcomes. Spearman's rank correlation coefficient was used to assess relationships between variables. RESULTS: The median age was highest in the low-dose group at 7 years, compared to 5.5 years in the medium-dose group and 6 years in the high-dose group (P < 0.001). The body mass index (BMI) was also highest in the low-dose group at 16.12, followed by 14.86 in the medium-dose group and 14.58 in the high-dose group (P < 0.001). More severe radiographic findings, longer hospital stays, and greater incidence of hypoxia were noted in the high-dose group (P < 0.05). Additionally, significant increases in white blood cells, C-reactive protein, procalcitonin, lactate dehydrogenase (LDH), alanine transaminase, aspartate transaminase, ferritin, erythrocyte sedimentation rate, and D-dimer levels were observed in the high-dose group (P < 0.05). Specifically, LDH and ferritin were markedly higher in the high-dose group, with levels at 660.5 U/L and 475.05 ng/mL, respectively, compared to 450 U/L and 151.4 ng/mL in the medium-dose group, and 316.5 U/L and 120.5 ng/mL in the low-dose group. Correlation analysis indicated that LDH and ferritin levels were significantly and positively correlated with glucocorticoid dose (Spearman ρ = 0.672 and ρ = 0.654, respectively; P < 0.001). CONCLUSIONS: Serum LDH and ferritin levels may be useful biomarkers for determining the appropriate corticosteroid dosage in treating children with RMPP.

A ferritin-based nanoparticle displaying a neutralizing epitope for foot-and-mouth disease virus (FMDV) confers partial protection in guinea pigs.

BACKGROUND: Foot-and-mouth disease (FMD) is a devastating disease affecting cloven-hoofed animals, that leads to significant economic losses in affected countries and regions. Currently, there is an evident inclination towards the utilization of nanoparticles as powerful platforms for innovative vaccine development. Therefore, this study developed a ferritin-based nanoparticle (FNP) vaccine that displays a neutralizing epitope of foot-and-mouth disease virus (FMDV) VP1 (aa 140-158) on the surface of FNP, and evaluated the immunogenicity and protective efficacy of these FNPs in mouse and guinea pig models to provide a strategy for developing potential FMD vaccines. RESULTS: This study expressed the recombinant proteins Hpf, HPF-NE and HPF-T34E via an E. coli expression system. The results showed that the recombinant proteins Hpf, Hpf-NE and Hpf-T34E could be effectively assembled into nanoparticles. Subsequently, we evaluated the immunogenicity of the Hpf, Hpf-NE and Hpf-T34E proteins in mice, as well as the immunogenicity and protectiveness of the Hpf-T34E protein in guinea pigs. The results of the mouse experiment showed that the immune efficacy in the Hpf-T34E group was greater than the Hpf-NE group. The results from guinea pigs immunized with Hpf-T34E showed that the immune efficacy was largely consistent with the immunogenicity of the FMD inactivated vaccine (IV) and could confer partial protection against FMDV challenge in guinea pigs. CONCLUSIONS: The Hpf-T34E nanoparticles stand out as a superior choice for a subunit vaccine candidate against FMD, offering effective protection in FMDV-infected model animals. FNP-based vaccines exhibit excellent safety and immunogenicity, thus representing a promising strategy for the continued development of highly efficient and safe FMD vaccines.

Serum Iron and Ferritin Levels in Beta Thalassemia Carriers in Duhok Governorate, Iraq.

Background Thalassemia and iron deficiency anemia (IDA) account for most cases of microcytic hypochromic anemia. It is a common misconception that iron deficiency does not occur in thalassemia. However, studies have found that iron deficiency can coexist in carriers of beta thalassemia. Objective The aim of this study was to determine the prevalence of iron deficiency and iron overload in carriers of beta thalassemia in Duhok, Iraq. Patients and methods This prospective cross-sectional study included 250 patients with beta thalassemia carriers attending Kurdistan Private Hospital Laboratory Department from July 2021 to June 2023. Patients with microcytic hypochromic blood picture were tested for HbA2 levels, and those with a level >3.7% were included in the study and were tested for serum iron and serum ferritin levels. Results The age range was 15-80 years, with a mean of 25 years, and the male-to-female ratio was 1.5:1. The prevalence of iron deficiency in beta thalassemia carriers was 16% (N = 40). The prevalence of iron overload was 8.4% (N = 21). There was a significant statistical difference among those with iron deficiency, normal iron status, and iron overload in terms of hemoglobin level (P=0.001), RBC count (P=0.012), HbA2 (P=0.015), and serum ferritin (P < 0.0001). Conclusion Iron deficiency is more prevalent in beta thalassemia carriers than iron overload, necessitating proper assessment of iron status in patients with beta thalassemia carriers. Those with abnormal iron status need effective treatment to optimize the overall outcomes in patients with beta thalassemia carriers.

Unveiling the stochastic nature of human heteropolymer ferritin self-assembly mechanism.

Despite ferritin's critical role in regulating cellular and systemic iron levels, our understanding of the structure and assembly mechanism of isoferritins, discovered over eight decades ago, remains limited. Unveiling how the composition and molecular architecture of hetero-oligomeric ferritins confer distinct functionality to isoferritins is essential to understanding how the structural intricacies of H and L subunits influence their interactions with cellular machinery. In this study, ferritin heteropolymers with specific H to L subunit ratios were synthesized using a uniquely engineered plasmid design, followed by high-resolution cryo-electron microscopy analysis and deep learning-based amino acid modeling. Our structural examination revealed unique architectural features during the self-assembly mechanism of heteropolymer ferritins and demonstrated a significant preference for H-L heterodimer formation over H-H or L-L homodimers. Unexpectedly, while dimers seem essential building blocks in the protein self-assembly process, the overall mechanism of ferritin self-assembly is observed to proceed randomly through diverse pathways. The physiological significance of these findings is discussed including how ferritin microheterogeneity could represent a tissue-specific adaptation process that imparts distinctive tissue-specific functions to isoferritins.

The association between ferritin levels and all-cause mortality in stroke patients.

Purpose: The purpose of study was to describe the association between ferritin and all-cause mortality of cases with stroke. Methods: Clinical data derived from Multiparameter Intelligent Monitoring in Intensive Care were analyzed. The primary endpoint was 30-day mortality. The potential prognostic roles of Ferritin L were analyzed by Cox proportional hazard models. The independent prognostic roles of Ferritin L in the cases were analyzed by smooth curve fitting. Results: Concerning 30-day mortality, the HR (95% CI) for a high Ferritin (≥373) was 1.925 (1.298, 2.854; p = 0.00113), compared to a low ferritin (< 373). After adjusting for multiple confounders, the HR (95% CI) for a high Ferritin (≥373) was 1.782 (1.126, 2.820; p = 0.01367), compared to a low Ferritin (< 373). A non-linear association between Ferritin and 30-day mortality was found. Using recursive algorithm and two-piecewise linear regression model, inflection point (IP) was calculated, which was 2,204. On the left side of the IP, there was a positive relationship between Ferritin and 30-day mortality, and the effect size, 95% CI and p value were 1.0006 (1.0004, 1.0009) p < 0.0001, respectively. On the right of the IP, the effect size, 95% CI and p value were 1.0000 (1.0000, 1.0000) and 0.3107, respectively. Conclusion: Ferritin was associated with increased risk of stroke; it is important to further examine the association if the increased uric acid would increase the outcome of stroke in a longitudinal study. The non-linear relationship between Ferritin and all-cause mortality of stroke was observed. Ferritin was a risk factor for the outcome of stroke when ferritin was <2204.

Immunohistochemical Study of Human Mitochondrial Ferritin in the Substantia Nigra Following Subarachnoid Hemorrhage.

Mitochondrial ferritin (FtMt) is a novel ferritin that sequesters iron and plays a protective role against oxidative stress. FtMt shares a high homology with H-ferritin but is expressed only in the brain, heart, and testis. In the midbrain, FtMt expression is observed in the substantia nigra. FtMt plays a neuroprotective role in the pathology of neurodegenerative diseases such as Parkinson's disease, where excessive iron induces oxidative stress, causing cell death. Herein, we investigated FtMt immunoreactivity in the brains of patients with subarachnoid hemorrhage (SAH). Double immunofluorescence labeling of tyrosine hydroxylase (TH) and FtMt showed high colocalization in the substantia nigra pars compacta (SNc) in control and SAH cases. However, in SAH cases, FtMt immunoreactivity was observed in some TH-negative neurons. Double immunofluorescence labeling of glial cell markers and FtMt showed no apparent colocalization. The number and ratio of FtMt-positive but TH-negative neurons significantly differed between the control and SAH groups. Prussian blue staining in SAH cases showed positive iron staining over a wide surface range and the substantia nigra. Thus, FtMt may be related to iron dynamics in the substantia nigra following subarachnoid hemorrhage.

Can ferritin be a surrogate marker for CD4 cells in human immunodeficiency virus patients? A cross-sectional study of association of serum ferritin levels with immunological staging of human immunodeficiency virus patients.

Introduction: The human immunodeficiency virus (HIV)/AIDS in India came into public view in 1986 with the detection of the first case of HIV in Chennai, Tamil Nadu, and the first AIDS case in Mumbai, Maharashtra in 1987. In acute phase response, iron distribution occurs in the liver and mononuclear phagocytic system. A high prevalence of elevated serum ferritin levels is reported in HIV infection and serum ferritin levels increase with the clinical worsening of infection and with decreasing CD4 lymphocyte counts. This study is designed to find the role of acute phase reactant serum ferritin in the progression of the disease of HIV which is complicated by opportunistic infections, by finding the correlation of serum ferritin with immunological stages of HIV. Materials and Methods: This cross-sectional study was conducted on 75 patients admitted to various wards of the Department of Medicine or attending medicine outdoor or ART Centre, Maharana Bhupal Government Hospital, RNT Medical College Udaipur. Serum ferritin, total iron binding capacity, and total serum iron were analyzed in Cobas® analyzer. CD4 cells are measured using the flow cytometry technique. The results were tabulated and subjected to statistical analysis. Results and Conclusion: There was a negative correlation among serum ferritin and CD4 cells with r = -0.195 which was statistically significant (P < 0.05). As the CD4 cell count decreased incidence of serum ferritin increased. Elevation of serum ferritin levels is associated with a low count of the CD4+ in HIV-diagnosed patients. In a patient diagnosed with HIV, elevated serum ferritin indicates underlying inflammatory pathology. Serum ferritin can be used as a guide to further evaluation of underlying disease in HIV patients.

Enhancing Nanobody Immunoassays through Ferritin Fusion: Construction of a Salmonella-Specific Fenobody for Improved Avidity and Sensitivity.

Nanobodies (Nbs) serve as powerful tools in immunoassays. However, their small size and monovalent properties pose challenges for practical application. Multimerization emerges as a significant strategy to address these limitations, enhancing the utilization of nanobodies in immunoassays. Herein, we report the construction of a Salmonella-specific fenobody (Fb) through the fusion of a nanobody to ferritin, resulting in a self-assembled 24-valent nanocage-like structure. The fenobody exhibits a 35-fold increase in avidity compared to the conventional nanobody while retaining good thermostability and specificity. Leveraging this advancement, three ELISA modes were designed using Fb as the capture antibody, along with unmodified Nb422 (FbNb-ELISA), biotinylated Nb422 (FbBio-ELISA), and phage-displayed Nb422 (FbP-ELISA) as the detection antibody, respectively. Notably, the FbNb-ELISA demonstrates a detection limit (LOD) of 3.56 × 104 CFU/mL, which is 16-fold lower than that of FbBio-ELISA and similar to FbP-ELISA. Moreover, a fenobody and nanobody sandwich chemiluminescent enzyme immunoassay (FbNb-CLISA) was developed by replacing the TMB chromogenic substrate with luminal, resulting in a 12-fold reduction in the LOD. Overall, the ferritin-displayed technology represents a promising methodology for enhancing the detection performance of nanobody-based sandwich ELISAs, thereby expanding the applicability of Nbs in food detection and other fields requiring multivalent modification.

Unveiling childhood asthma: Exploring biomarkers, zinc, and beyond.

This editorial discusses a case-control study by Ibrahim et al, published in the recent issue of the World Journal of Clinical Pediatrics. Childhood bronchial asthma is a chronic inflammatory respiratory disease. It was found that an increase in oxidative stress leads to a decrease in antioxidants causing oxidative damage to mitochondrial respiratory chain complexes resulting in the inflammation of the airway, hypersecretion of mucus causing a cascade of clinical manifestations ranging from recurrent episodes of coughing, wheezing, and breathlessness to shortness of breath. Since oxidative stress mediates the inflammatory response in asthma, the supplementation of anti-oxidants can be one strategy to manage this disease. Zinc is one such antioxidant that has attracted much attention about asthma and airway inflammation. Zinc is a crucial trace element for human metabolism that helps to regulate gene expression, enzyme activity, and protein structure. Apart from zinc, free serum ferritin levels are also elevated in case of inflammation. Several previous studies found that ferritin levels may also help determine the pathology of disease and predict prognosis in addition to tracking disease activity. However, this study's results were different from the findings of the previous studies and the zinc levels did not show a significant difference between asthmatic children and non-asthmatic children but ferritin levels were significantly high in asthmatic children as compared to the controls. Hence, the possible role of the biochemical nutritional assessment including zinc and ferritin as biomarkers for asthma severity should be assessed in the future.

Continuous training in young athletes decreases hepcidin secretion and is positively correlated with serum 25(OH)D and ferritin.

Background: Iron deficiency is known to impair muscle function and reduce athletic performance, while vitamin D has been reported to induce iron deficiency. However, the mechanism underlying exercise-induced changes in iron metabolism and the involvement of vitamins in this mechanism are unclear. The present study examined changes in biological iron metabolism induced by continuous training and the effects of vitamin D on these changes. Methods: Diet, physical characteristics, and blood test data were collected from 23 female high school students in a dance club on the last day of each of a 2-month continuous training period and a 2-week complete rest periods. Results: Serum hepcidin-25 levels were significantly lower during the training period than the rest period (p = 0.013), as were the red blood cell count, hemoglobin, and hematocrit (all p < 0.001). Serum erythropoietin was significantly higher (p = 0.001) during the training period. Significant positive correlations were observed between 25(OH)D levels and serum iron, serum ferritin, and transferrin saturation during the training period. Multiple regression analysis with serum 25(OH)D level as the dependent variable and serum ferritin and iron levels as independent variables during the training period revealed a significant association with serum ferritin. Conclusion: Continuous training may promote hemolysis and erythropoiesis, contributing to the suppression of hepcidin expression. The relationship between serum 25(OH)D and iron in vivo may be closely related to metabolic changes induced by the exercise load.

Update on iron supplementation in patients with cancer-related anemia.

INTRODUCTION: Numerous clinical trials affirm the efficacy and safety of IV iron to treat cancer-related anemia (CRA). Nonetheless, evaluation and treatment of CRA remains suboptimal. AREAS COVERED: This review summarizes CRA therapy with a focus on iron deficiency and its treatment. The literature search was conducted using the National Library of Medicine (PubMed) database from 2004 to 2024. Topics reviewed include CRA pathophysiology, laboratory diagnosis of iron deficiency, a summary of clinical trial results using IV iron to treat CRA, and safety aspects. EXPERT OPINION: Despite overwhelming positive efficacy and safety data, IV iron remains underutilized to treat CRA. This is likely due to persistent (unfounded) concerns about IV iron safety and lack of physician awareness of newer clinical trial data. This leads to poor patient quality of life and patient exposure to anemia treatments that have greater safety risks than IV iron. Solutions to this problem include increased educational efforts and considering alternative treatment models in which other providers separately manage CRA. The recent availability of new oral iron therapy products that are effective in treating anemia of inflammation has the potential to dramatically simplify the treatment of CRA.

Correlation between plasma biochemical parameters and cardio-hepatic iron deposition in thalassemia major patients.

INTRODUCTION: Major Thalassemia patients suffer from iron overload and organ damage, especially heart and liver damage. Early diagnosis and treatment with a chelator can reduce the complications and mortality of iron overload. Therefore, we aimed to investigate the biochemical and hematological predictors as an alternative and indirect indicator of iron deposition in heart and liver cells in comparison with the MRI T2* method as the gold standard. MATERIAL AND METHOD: MRI T2* was evaluated in the heart and liver tissues of 62 major beta-thalassemia patients undergoing regular transfusion and chelator therapy. Biochemical and hematological factors were also measured, including serum ferritin, serum electrolytes, liver enzymes, hemoglobin, blood glucose, and serum magnesium. The correlation between these factors was assessed using statistical evaluations. RESULT: Serum ferritin had a positive and significant correlation with liver siderosis based on MRI T2* (p-value = .015), and no significant association was observed with cardiac siderosis (p-value = .79). However, there was a significant positive correlation between cardiac iron deposition and fasting blood sugar level (p-value = -.049), and plasma level of liver enzymes (alanine aminotransferase (ALT) (p-value = .001), aspartate aminotransferase (AST ((p-value = .01)). Moreover, there was a significant negative correlation between cardiac iron overload and plasma magnesium level (p-value = .014). According to MRI T2*, there was no significant correlation between cardiac and hepatic iron overload (p value = .36). CONCLUSION: An increase in blood sugar or liver enzymes and a decrease in serum magnesium was associated with an increase in cardiac iron overload based on MRI T2*. Liver iron overload based on MRI T2* had a significant correlation with serum ferritin.

Resolution of extravascular hemolysis with oral iptacopan monotherapy in a patient with treatment experienced paroxysmal nocturnal hemoglobinuria (PNH).

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematologic disorder characterized by a loss of glycosyl-phosphatidyl-inositol-linked (GPI) proteins on various hematopoietic cells. Some GPI proteins are involved in the regulation of the complement system, and their absence renders erythrocytes susceptible to complement-mediated lysis. Current standard of care in PNH is to block the complement system at the level of C5 using ravulizumab or eculizumab; however, some patients with PNH may develop extravascular hemolysis (EVH) during treatment with C5 inhibitors. The proximal complement inhibitor iptacopan has recently been shown to be efficacious in patients with PNH. This article reports on a 43-year-old female patient with PNH who was successfully treated with iptacopan. The patient had received ravulizumab for several years and developed a clinically relevant EVH. After obtaining informed consent, the patient received oral iptacopan 200 mg twice daily and ravulizumab was discontinued. Over the next few weeks hemoglobin levels and reticulocyte counts normalized. The patient reported mild flushes with erythema, chills, and mild muscle pain, all of which resolved during follow-up. No breakthrough hemolysis occurred, and no severe adverse events were recorded.

Bioaccessibility and Caco-2 Cell Uptake of Iron Chlorophyllin Using A Biologically Relevant Digestion Model.

Iron deficiency remains a top nutrient deficiency worldwide. Iron chlorophyllin (IC), a compound structurally analogous to heme, utilizes the protoporphyrin ring of chlorophyll to bind iron. IC has previously been shown to deliver more iron to Caco-2 cells than FeSO4, the most common form prescribed for supplementation. However, previous test conditions used digestive conditions outside of those observed in humans. This study sought to assess IC bioaccessibility and Caco-2 cell uptake using physiologically relevant digestive solutions, pH, and incubation time, as compared to other iron sources (i.e. FeSO4, and hemoglobin (Hb)). Co-digestion with ascorbic acid (AA) and albumin was also investigated. Following gastric, duodenal, and jejunal digestion, IC-bound iron was less bioaccessible than iron delivered as FeSO4, and IC-bound iron was less bioaccessible than Hb-bound iron. IC-bound iron bioaccessibility was not affected by AA and was enhanced 2x with co-digested with a low dose of albumin. However, Caco-2 cell incubation with IC-containing digesta increased cell ferritin 2.5x more than FeSO4 alone, and less than Hb. IC with AA or with 400 mg albumin also increased cell ferritin more than IC alone, with the greatest increases observed following incubation of digesta containing IC + AA + 400 mg albumin. These results suggest IC can serve as an improved source of iron for supplementation as compared to FeSO4. These results also support further in vivo investigations of IC-based iron delivery in populations at risk of iron deficiency.

Diagnostic pitfalls in assessment of ferritin following CAR-T-cell therapy: Understanding the hook effect.

The hook effect is a well-described but clinically underappreciated immunoassay interference, where a falsely lowered result is caused by analyte excess. We describe a situation in which ferritin immunoassay results from a 27-year-old female with immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome were more than 1000 times lower at a reference laboratory than those determined in-house after dilution. This case underscores the importance for clinical care providers to be aware of the impact of the hook effect on ferritin measurements, and to promptly communicate with the laboratory when there are discrepancies between clinical symptoms and test results.

Erythropoiesis-stimulating agent hyporesponsiveness was associated with worse survival of hemodialysis patients independent of the serum ferritin level.

INTRODUCTION: Ferritin level and erythropoiesis-stimulating agent (ESA) responsiveness are each associated with hemodialysis patient survival. We assessed interrelationships between these two vs. survival. METHODS: Patients in the Japan Dialysis Outcomes and Practice Patterns Study Phases 4-6 (2009-2018) were included. All-cause mortality associations were assessed with progressive adjustment to evaluate covariate influence. RESULTS: During follow-up (median 2.6 years), 773 of 5154 patients died. After covariate adjustment, the mortality hazard ratio (HR) was 0.99 (95% CI: 0.81, 1.20) for low serum ferritin and 1.12 (CI: 0.89, 1.41) for high serum ferritin. By contrast, mortality risk with elevated ESA resistance index (ERI) persisted after covariate adjustment (HR 1.44, CI [1.17-1.78]). The serum ferritin and ERI interaction was not significant; p > 0.96 across all models. CONCLUSIONS: Japanese hemodialysis patients with high ERI experienced worse survival independent of serum ferritin levels, highlighting the importance of identifying and mitigating ESA hyporesponsiveness among dialysis patients.