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Abstract: Iron overload and its complications are recognized to be morbid and fatal in patients with congenital hemolytic anemias. In patients with iron overload caused by congenital hemolytic anemias, there has been no study evaluating the dose-response relationship between serum markers of iron overload and long-term health complications. Filling this critical gap was the aim of this study. We evaluated outcomes in a 5-hospital observational cohort study of adults with congenital hemolytic anemias diagnosed with iron overload over a 40-year period and assessed associations between depth and duration of iron overload, as well as clinical complications including diabetes, heart disease, malignancy, bone density disorders, and death. One hundred seventy patients with congenital hemolytic anemias developing iron overload were included. More years experienced of ferritin >500 ng/mL and >1000 ng/mL were associated with the development of diabetes mellitus, with adjusted odds ratios (ORs) of 2.61 per 10-year increment (P = .034) and 3.24 per 10-year increment (P = .035), respectively. More years experienced of ferritin >1000 ng/mL were associated with the development of heart disease (adjusted OR, 5.30 per 10-year increment; P = .002). Peak lifetime ferritin of >10 000 ng/mL was associated with sixfold odds of developing diabetes (P = .04) and 10-fold odds of developing heart disease (P = .007). A peak ferritin >10 000 ng/mL was associated with an increase in mortality (adjusted OR, 6.77; P = .033). In conclusion, iron overload in patients with congenital hemolytic anemias is associated with diabetes mellitus, cardiac disease, and death. Prolonged exposure to relatively modest iron overload was associated with nearly threefold increased odds of diabetes., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Strenuous physical training increases total blood volume (BV) through expansion of plasma volume (PV) and red cell volume (RCV). In contrast, exogenous erythropoietin (EPO) treatment increases RCV but decreases PV, rendering BV stable or slightly decreased. This study aimed to determine the combined effects of strenuous training and EPO treatment on BV and markers of systemic and muscle iron homeostasis. In this longitudinal study, eight healthy nonanemic males were treated with EPO (50 IU/kg body mass, three times per week, sc) across 28 days of strenuous training (4 days/wk, exercise energy expenditures of 1,334 ± 24 kcal/day) while consuming a controlled, energy-balanced diet providing 39 ± 4 mg/day iron. Before (PRE) and after (POST) intervention, BV compartments were measured using carbon monoxide rebreathing, and markers of iron homeostasis were assessed in blood and skeletal muscle (vastus lateralis). Training + EPO increased ( P < 0.01) RCV (13 ± 6%) and BV (5 ± 4%), whereas PV remained unchanged ( P = 0.86). The expansion of RCV was accompanied by a large decrease in whole body iron stores, as indicated by decreased ( P < 0.01) ferritin (-77 ± 10%) and hepcidin (-49 ± 23%) concentrations in plasma. Training + EPO decreased ( P < 0.01) muscle protein abundance of ferritin (-25 ± 20%) and increased ( P < 0.05) transferrin receptor (47 ± 56%). These novel findings illustrate that strenuous training combined with EPO results in both increased total oxygen-carrying capacity and hypervolemia in young healthy males. The decrease in plasma and muscle ferritin suggests that the marked upregulation of erythropoiesis alters systemic and tissue iron homeostasis, resulting in a decline in whole body and skeletal muscle iron stores. NEW & NOTEWORTHY Strenuous exercise training combined with erythropoietin (EPO) treatment increases blood volume, driven exclusively by red cell volume expansion. This hematological adaptation results in increased total oxygen-carrying capacity and hypervolemia. The marked upregulation of erythropoiesis with training + EPO reduces whole body iron stores and circulating hepcidin concentrations. The finding that the abundance of ferritin in muscle decreased after training + EPO suggests that muscle may release iron to support red blood cell production.

Objective: Adult-onset Still's disease (AOSD) and secondary hemophagocytic lymphohistiocytosis (sHLH) are both hyperferritinemic cytokine storm syndromes that can be difficult to distinguish from each other in hospitalized patients. The objective of this study was to compare the inflammatory markers ferritin, D-dimer, C-reactive protein (CRP), and soluble CD25 (sCD25) in patients with AOSD and sHLH. These four markers were chosen as they are widely available and represent different aspects of inflammatory diseases: macrophage activation (ferritin); endothelialopathy (D-dimer); interleukin-1/interleukin-6/tumour necrosis factor elevation (CRP) and T cell activation (sCD25)., Methods: This was a single-center retrospective study. Patients diagnosed by the Hematology service at Vancouver General Hospital for AOSD or sHLH from 2009 to 2023 were included., Results: There were 16 AOSD and 44 sHLH patients identified. Ferritin was lower in AOSD than HLH (median 11 360 μg/L vs. 29 020 μg/L, p = .01) while D-dimer was not significantly different (median 5310 mg/L FEU vs. 7000 mg/L FEU, p = .3). CRP was higher (median 168 mg/L vs. 71 mg/L, p <.01) and sCD25 was lower (median 2220 vs. 7280 U/mL, p = .004) in AOSD compared to HLH. The combined ROC curve using CRP >130 mg/L and sCD25< 3900 U/mL to distinguish AOSD from HLH had an area under the curve (AUC) of 0.94 (95% confidence interval 0.93-0.97) with sensitivity 91% and specificity 93%., Conclusions: These findings suggest that simple, widely available laboratory tests such as CRP and sCD25 can help clinicians distinguish AOSD from HLH in acutely ill adults with extreme hyperferritinemia. Larger studies examining a wider range of clinically available inflammatory biomarkers in a more diverse set of cytokine storm syndromes are warranted., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Aim: Out-of-hospital cardiac arrest (OHCA) is a major health concern in Western societies. Poor outcome after OHCA is determined by the extent of hypoxic-ischemic encephalopathy (HIE). Dysregulation of iron metabolism has prognostic relevance in patients with ischemic stroke and sepsis. The aim of this study was to determine whether serum iron parameters help to estimate outcomes after OHCA., Methods: In this prospective single-center study, 70 adult OHCA patients were analyzed. Serum ferritin, iron, transferrin (TRF), and TRF saturation (TRFS) were measured in blood samples drawn on day 0 (admission), day 2, day 4, and 6 months after the return of spontaneous circulation (ROSC). The association of 4 iron parameters with in-hospital mortality, neurological outcome (cerebral performance category [CPC]), and HIE was investigated by receiver operating characteristics and multivariate regression analyses., Results: OHCA subjects displayed significantly increased serum ferritin levels on day 0 and lowered iron, TRF, and TRFS on days 2 and 4 after ROSC, as compared to concentrations measured at a 6-month follow-up. Iron parameters were not associated with in-hospital mortality or neurological outcomes according to the CPC. Ferritin on admission was an independent predictor of features of HIE on cranial computed tomography and death due to HIE., Conclusion: OHCA is associated with alterations in iron metabolism that persist for several days after ROSC. Ferritin on admission can help to predict HIE., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Iron deficiency (ID) without anemia is common in children with newly diagnosed celiac disease (CD). We aimed to assess the effect of iron supplementation versus no treatment on ferritin levels in newly diagnosed CD patients with ID adhering to a gluten-free diet (GFD). A retrospective review of children < 18 years, with low ferritin (≤ 10 ng/mL) and normal hemoglobin levels diagnosed between 12.2018 and 12.2021. We compared hemoglobin and ferritin levels between patients who received supplemental iron to those who did not. Data, including demographics, laboratory tests, and anthropometrics, were collected at baseline, and at 6 and 12 months following the initiation of the GFD. Adherence to GFD was assessed at each visit. Among 304 children diagnosed during the study period, 43 (14.1%) had iron deficiency anemia and 60 (19.7%) ID without anemia. Among children with ID, 29 (48%) were female, mean age 7.3 ± 3.9 years. Twenty-nine (48%) children received iron supplementation, and 31 (52%) did not. At the 12-month follow-up visit, tissue transglutaminase levels decreased significantly (p < 0.001), from a mean baseline level of 226.6 ± 47.8 to 34.5 ± 46 U/mL in children that received iron supplementation and from 234.2 ± 52.4 to 74.5 ± 88.7 U/mL in non-treated children, with no significant difference between the groups p = 0.22. Ferritin levels increased significantly (p < 0.001), from 9.0 ± 4.7 to 25.2 ± 20.8 ng/mL in patients who received supplementation and from 8.9 ± 3.8 to18.6 ± 9.5 ng/mL in patients who did not, with no significant difference between the groups (p = 0.46)., Conclusion: Most children with newly diagnosed celiac disease and iron deficiency, who adhere to GFD, will normalize ferritin levels within 12 months without the need of iron supplementation., What Is Known: • Iron deficiency and iron deficiency anemia are common in newly diagnosed celiac disease. • Improved iron absorption may follow mucosal healing process in patients adhering to a strict gluten-free diet., What Is New: • This single-center, retrospective cohort study evaluated the effect of iron supplementation versus no treatment on ferritin levels in children with newly diagnosed celiac disease with iron deficiency adhering to a gluten-free diet. • Most children with newly diagnosed celiac disease and iron deficiency, who adhere to gluten-free diet, will normalize ferritin levels within 12 months without the need of iron supplementation., (© 2024. The Author(s).)

Background: There is limited randomized controlled trial evidence to support the association between vitamin D deficiency and anemia risk, highlighting the necessity for further investigations into the role of vitamin D in influencing iron status., Objective: The aim of this study was to determine the effect of vitamin D3-fortified fruit drink consumption (4,000 IU) on vitamin D and iron status biomarkers among iron-deficient women (serum ferritin of <20 μg/L [to convert μg/L ferritin to ng/mL, multiply by 1])., Design: An 8-week double-blind randomized controlled trial was conducted., Subjects/setting: A total of 45 healthy, nonpregnant, nonlactating subjects aged 18 through 40 years (mean [SD] 25.3 [4.6] years) were included in the study, excluding those who donated blood 6 months prior, regularly consumed nutritional supplements, or had gastrointestinal or iron metabolic disorders., Intervention: Subjects were randomly assigned to receive either vitamin D3-fortified fruit drink or a placebo., Main Outcome Measures: Measurements of 25-hydroxyvitamin D (25[OH]D), serum ferritin, high-sensitivity C-reactive protein, and full blood count concentrations were obtained at baseline, interim, and post intervention., Statistical Analyses: A mixed model, repeated measures analysis of variance was used to analyze the intervention effect., Results: Attrition rate for the study was 13%, with 6 dropouts, and 39 subjects completed the study. Daily consumption of vitamin D3-fortified fruit drink in the intervention group resulted in significant increases in 25(OH)D and serum ferritin concentrations compared with the placebo group. The intervention group showed significantly higher mean (SD) changes (Δ) in both 25(OH)D (Δ 76.4 [30.2] nmol/L [to convert nmol/L 25(OH)D to ng/mL, multiply by .4] vs Δ -1.3 [10.7] nmol/L; P = .001) and serum ferritin concentrations (Δ 2.2 [4.2] μg/L vs Δ -0.3 [3.4] μg/L; P = .048) between baseline and post intervention. The other iron status biomarkers were not affected by the intervention., Conclusions: Our study found that daily vitamin D3-fortified fruit drink supplementation for 8 weeks effectively improved 25(OH)D and iron stores, indicated by increased serum ferritin concentrations, in iron-deficient women. Further research is needed to evaluate its safety, efficacy, feasibility, and optimal food fortification in diverse populations., (Copyright © 2024 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: Sudanese children with End-Stage Kidney Disease (ESKD) often show limited improvement in hemoglobin levels despite treatment with recombinant human erythropoietin (rHuEPO). This study aims to assess the response to rHuEPO therapy by analyzing β-globin mRNA expression and reticulocyte parameters. Additionally, it classifies anemia among Sudanese pediatric patients based on iron status, considering age and gender as biological markers for evaluating treatment response., Methods: A prospective observational cohort study was conducted from January 2019 to February 2020 in Khartoum, Sudan, involving 45 anemic children aged 2 to 15 years diagnosed with ESKD. The treatment protocol included rHuEPO injections and maintenance hemodialysis. Laboratory assessments consisted of complete blood count (CBC), absolute reticulocyte count, ferritin, and transferrin measurements. β-globin mRNA expression was quantified using reverse transcription polymerase chain reaction (RT-PCR), and reticulocyte parameters, including Reticulocyte Hemoglobin Content (CHr), percentage of hypochromic reticulocytes (HYPO%), and Immature Reticulocyte Fraction (IRF), were measured via flow cytometry., Results: Significant variations in hemoglobin levels were observed across different age groups (p = 0.011). Gender analysis revealed a significant association with IRF, showing a lower IRF in male patients (p = 0.017). However, there were no significant differences in hemoglobin levels between genders (p = 0.999). β-globin mRNA expression showed considerable variability, with a strong positive correlation with hemoglobin levels (r = 0.875, p < 0.0001)., Conclusion: Age and gender significantly influence treatment responses in children with ESKD, highlighting the need to consider growth physiology in anemia management. This study underscores the variability in β-globin mRNA expression and its association with Flow Cytometry parameters, demonstrating their effectiveness in evaluating iron status and guiding rHuEPO dosage., (© 2024. The Author(s).)

With the aging of the global population and the increase in the number of people with conditions such as obesity, the incidence of osteoarthritis (OA) is increasing annually. Clinical studies have shown that excessive accumulation of iron in joints is associated with age-related OA. However, there have been no reports on the relationship between iron metabolism and osteoarthritis. A STROBE-compliant cross-sectional observational study, was carried out and analyzed from the National Health and Nutrition Examination Survey from 2001 to 2020, including data on serum iron, transferrin saturation, serum ferritin, total iron-binding capacity, and transferrin receptors, as well as data on osteoarthritis. This cross-sectional study was conducted to explore the relationship between serum iron levels, osteoarthritis, and related metabolic factors. By adjusting the model and using quantile logistic regression models, the interaction between human body iron content and the aforementioned variables was analyzed. A total of 56,323 participants over 5 cycles were assessed for iron levels. After adjusting the model for age, sex, race, education level, marital status, total energy intake, physical activity, drinking, BMI, smoking, hypertension, and diabetes, we found that in different quantile regression results, serum iron was associated with OA, Q4: OR = 1.231 (95%CI: 1.009-1.501, P < .05). Ferritin is associated with OA, Q2: OR = 1.309 (95%CI: 1.012-1.692, P < .05); Q3: OR = 1.424 (95%CI: 1.129-1.797, P < .01); Q4: OR = 1.280 (95%CI: 1.013-1.616, P < .05). This cross-sectional study found that serum iron and transferrin saturation levels were positively correlated with OA incidence, suggesting that iron overload is a risk factor for OA. Large-sample prospective cohort studies are needed to confirm the correlation between iron overload and OA., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the short-term and long-term efficacy and safety of thalidomide in the treatment of intermediate and severe β-thalassemia. We analyzed patients with intermediate and severe β-thalassemia treated at our hospital from February 2019 to February 2024. Patients who received treatment for more than 3 months were included. The efficacy of thalidomide was assessed by comparing changes in hemoglobin (Hb), ferritin, bilirubin, and Hb electrophoresis before and after treatment. Adverse drug reactions during treatment were also recorded. A total of 42 β-thalassemia patients were included, with thalidomide dosages ranging from 75 to 150 mg/d. The response rates at 1, 3, and 6 months of treatment were 73.8% (31/42), 75.0% (24/32), and 94.7% (18/19), respectively. The increase in Hb levels was primarily attributed to fetal hemoglobin (HbF). After 1 month of treatment, the HbF percentage increased from a baseline of 34.04 ± 27.58% to 56.25 ± 28.40% (P < .001). At 3 and 6 months, HbF further increased to 67.21 ± 27.12% (P < .001) and 73.93 ± 22.96% (P < .001), respectively. The average duration of thalidomide treatment was 25.3 ± 9.2 months (range: 4-60 months), with 6 patients treated for over 60 months and 18 patients for over 48 months. Two homozygous patients who failed thalidomide treatment achieved Hb levels above 100 g/L and discontinued transfusion therapy after 3 months of hydroxyurea treatment. The most common adverse reaction was somnolence, which was mild and tolerable. Thalidomide demonstrates significant and sustained therapeutic effects in β-thalassemia patients. The adverse reactions are mild and tolerable, allowing patients to continue treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Transfusion dependent β-thalassemia is a genetic blood disorder characterized by chronic anaemia. Blood transfusion is lifesaving but comes at a cost. Iron overload emerges as a prime culprit as a free radicals damage endothelial cells. Chronic anaemia further disrupts oxygen delivery, exacerbating the oxidative stress. Increased levels of met-haemoglobin and malondialdehyde compromise endothelial function. This research sheds light on the impact of met-haemoglobin and oxidative stress on endothelial function in 50 patients with transfusion dependent β-thalassemia major compared to 50 healthy individuals as control. Blood samples were collected & subjected to CBC, biochemical analysis including creatinine, ferritin, CRP, LDH, and HCV antibodies. Oxidative stress was assessed using met-haemoglobin & malondialdehyde. Endothelial dysfunction was evaluated by endothelial activation and stress index (EASIX). EASIX, met-haemoglobin and malondialdehyde were significantly increased in patients (1.44 ± 0.75, 2.07 ± 0.2, 4.8 ± 0.63; respectively) compared to the control (0.52 ± 0.24,0.88 ± 0.34,0.8 ± 0.34; respectively). Significant strong positive correlation was found between EASIX and met-haemoglobin, malondialdehyde, serum ferritin and CRP (P = 0.00, r = 0.904, P = 0.00, r = 0.948, P = 0.00, r = 0.772, P = 0.00, r = 0.971; respectively. Met-haemoglobin as well as EASIX should be routinely estimated to assess endothelial function especially before the decision of splenectomy. Antioxidant drugs should be supplemented., (© 2024. The Author(s).)

Preterm infants are most at risk of iron deficiency. However, our knowledge of the regulation of iron homeostasis in preterm infants is poor. The main goal of our research was to develop and validate an animal model of human prematurity to assess iron status in preterm infants. We performed a cesarean section on sows on the 109th day of pregnancy, which corresponds to the last trimester of human pregnancy. Preterm piglets showed decreased body weight, red blood cell indices, plasma iron level and transferrin saturation. Interestingly, higher hepatic and splenic non-heme iron content and plasma and hepatic ferritin levels were found in premature piglets compared with term ones. In addition, premature piglets showed higher mRNA levels of iron-regulatory hormone hepcidin in the liver than term animals, which have not been reflected in higher plasma hepcidin-25 levels. We also showed changes in hepcidin regulators, including hepatic bone morphogenetic protein 6, plasma erythroferrone and growth differentiation factor 15 in preterm piglets. Consequently, no difference was observed in iron-exporter ferroportin levels in the spleen and liver. Overall, it seems that premature piglets show a pattern of iron metabolism characteristic of functional iron deficiency and iron accumulation in the tissue.

Introduction: Ferroportin (Fpn) is the only known iron exporter and plays an essential role in iron homeostasis. Serum concentrations of Fpn in health and/or diseased states are still mostly unknown. Therefore, the aim of this study was to determine the concentration of Fpn in the serum of women of reproductive age (WRA) for the first time, and to establish whether there is a difference in the concentration of Fpn according to ferritin status., Materials and Methods: This research included 100 WRA (18-45 years, C-reactive protein (CRP) < 5 mg/L, hemoglobin > 120 g/L). Serum Fpn was measured using Enzyme Linked Immunosorbent Assay (ELISA) method on the analyzer EZ Read 800 Plus (Biochrom, Cambridge, UK). Reference interval was calculated using the robust method., Results: The median concentration of Fpn in the whole study group was 9.74 (5.84-15.69) µg/L. The subgroup with ferritin concentration > 15 µg/L had a median Fpn concentration 15.21 (10.34-21.93) µg/L, which significantly differed from Fpn concentration in the subgroup with ferritin concentration ≤ 15 µg/L (5.93 (4.84-8.36) µg/L, P < 0.001). The reference limits for the Fpn were 2.26-29.81 µg/L with 90% confidence intervals (CI) of 1.78 to 2.83 and 25.37 to 34.33, respectively., Conclusions: The proposed reference interval could help in the future research on iron homeostasis both in physiological conditions and in various disorders, because this is the first study that measured Fpn concentration in a certain gender and age group of a healthy population., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)

Objectives: To define groups and characterize differences in the prognosis of patients with adult-onset Still's disease (AOSD)., Methods: We performed a retrospective cohort study. Patients with AOSD were grouped using hierarchical unsupervised cluster analysis according to age, sex, clinical features, and laboratory data. The primary endpoints were overall survival and drug-free remission rate., Results: A total of 153 patients with AOSD were placed into four clusters. Those in Cluster 1 had a young onset, tended to be female, and had fewer complications and moderate ferritin concentrations. Those in Cluster 2 had a young onset and had more complications and higher ferritin concentrations. Those in Cluster 3 had a young onset, tended to be male, and had no lymphadenopathy and fewer complications. Those in Cluster 4 had an older onset, tended to be female, and had more complications and higher ferritin concentrations. Overall survival tended to be lower (P = .0539) in Cluster 4, and drug-free remission was higher in Clusters 1, 2, and 3 [hazard ratios (HRs) 2.19, 3.37, and 3.62 vs. Cluster 4, respectively]., Conclusions: Four groups of AOSD that have distinct clinical manifestations, ferritin concentrations, severity, and drug-free remission rate were identified, which were lowest in Cluster 4., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Ferroptosis, a lipid peroxidation- and iron-mediated type of regulated cell death, relates to both neuroinflammation, which is common in relapsing-remitting multiple sclerosis (RRMS), and neurodegeneration, which is prevalent in progressive (P)MS. Currently, findings related to the molecular markers proposed in this paper in patients are scarce. We analyzed circulatory molecular indicators of the main ferroptosis-related processes, comprising lipid peroxidation (malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and hexanoyl-lysine adduct (HEL)), glutathione-related antioxidant defense (total glutathione (reduced (GSH) and oxidized (GSSG)) and glutathione peroxidase 4 (GPX4)), and iron metabolism (iron, transferrin and ferritin) to estimate their contributions to the clinical manifestation of MS and differences between RRMS and PMS disease course. In 153 patients with RRMS and 69 with PMS, plasma/serum lipid peroxidation indicators and glutathione were quantified using ELISA and colorimetric reactions, respectively. Iron serum concentrations were determined using spectrophotometry, and transferrin and ferritin were determined using immunoturbidimetry. Compared to those with RRMS, patients with PMS had decreased 4-HNE (median, 1368.42 vs. 1580.17 pg/mL; p = 0.03). Interactive effects of MS course (RRMS/PMS) and disease-modifying therapy status on MDA ( p = 0.009) and HEL ( p = 0.02) levels were detected. In addition, the interaction of disease course and self-reported fatigue revealed significant impacts on 4-HNE levels ( p = 0.01) and the GSH/GSSG ratio ( p = 0.04). The results also show an association of MS course ( p = 0.03) and EDSS ( p = 0.04) with GSH levels. No significant changes were observed in the serum concentrations of iron metabolism indicators between the two patient groups ( p > 0.05). We suggest circulatory 4-HNE as an important parameter related to differences between RRMS and PMS. Significant interactions of MS course and other clinically relevant parameters with changes in redox processes associated with ferroptosis support the further investigation of MS with a larger sample while taking into account both circulatory and central nervous system estimation.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading chronic liver disease worldwide. Emerging evidence suggests a close crosstalk between iron status and metabolic syndrome. Therefore, this cohort study aimed to investigate the relationship between serum iron status and all-cause mortality in individuals with MASLD., Methods: A total of 3393 subjects with MASLD identified by ultrasound from the Third National Health and Nutrition Examination Survey (NHANES III) were included in the analysis. Iron status indicators included serum iron, ferritin, transferrin saturation, total iron binding capacity, hemoglobin concentration, mean corpuscular hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin concentration. Cox proportional hazards models and restricted cubic spline models with adjustment for multiple confounders were applied. Stratified analyses were performed by sex and age., Results: During a median of 26.08 years of follow-up, high serum iron and transferrin saturation were significantly associated with reduced all-cause mortality in a linear pattern ( P overall <0.001). Compared with the lowest quartile, individuals with serum iron and transferrin saturation in the third or fourth quartile intervals had a 20-40% reduction in long-term mortality. However, there was no independent association of serum ferritin, total iron binding capacity, and red blood cell indices with all-cause mortality in MASLD., Conclusion: This study suggests that serum iron and transferrin saturation have the potential to serve as independent biomarkers of all-cause mortality in patients with MASLD and implies the therapeutic potential of modifying iron status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xia, Ni, Ni, Wu, Du, Wan and You.)

Recent research highlights the significant impact of the gut microbiota on health and disease. Thalassemia, a hereditary blood disorder, requires regular blood transfusions, leading to an accumulation of iron in the body. Such changes could potentially alter the intestinal microbiota, thereby increasing the susceptibility of thalassemic patients to infection. In this study, we analyzed the fecal microbiota of 70 non-transfusion-dependent (NTDT) β-thalassemia/HbE patients and 30 healthy controls. Our findings indicate that iron chelation intervention had no detectable effect on the microbiome profile of thalassemic patients. However, the cross-sectional analysis revealed that the bacterial diversity and community structure in patients were significantly less diverse and distinct compared to those of healthy subjects. Using reference frames, we were also able to demonstrate that bacterial taxa that are known to produce short chain fatty acids, from the genera Alistipes, Coprococcus, and Oscillospira, and those from the family Ruminococcaceae, were less prevalent in the patients. In contrast, bacterial taxa associated with an unhealthy gut, including the genus Clostridium and those from the families Fusobacteriaceae, Enterobacteriaceae, and Peptostrptococcaceae, were more prevalent in patients and found to be correlated with higher levels of ferritin. Collectively, these changes in the microbiota could be regarded as markers of raised ferritin levels, and therefore, awareness should be exercised as they could interfere, albeit indirectly, with the treatment of the co-morbidities of thalassemia., (© 2024. The Author(s).)

Ferritin is one of the most requested blood tests in both primary and inpatient care, and high values occur frequently. One of the greatest challenges in the investigation of hyperferritinemia is to determine if there is a presence of iron overload. Patient history (chronic liver disease, excessive alcohol consumption, hereditary factors), clinical features (metabolic syndrome, acute or chronic inflammation, infection, malignancy) and biochemical tests (ferritin, transferrin saturation, hemoglobin, liver enzymes, CRP/SR, phosphatidyl ethanol, lipid profile, glucose) facilitate the determination of the cause of hyperferritinemia. High transferrin saturation indicates iron overload, which is usually linked to hereditary hemochromatosis. In the case of homozygosity of the HFE mutation p.C282Y in the presence of hyperferritinemia, venesection can be started without further investigations, while in the absence of HFE mutations a possible iron excess must be validated with magnetic resonance imaging (MRI) for iron determination before venesection is started. Dysmetabolic iron overload syndrome (DIOS) or alcohol-related hemosiderosis can be treated with venesection in selected cases if there is a significant deposition of iron in the liver on MRI. An individual with ferritin below 1000 µg/L, a normal transferrin saturation, and normal liver tests does not need further investigations and can be followed in primary care. We propose an algorithm for the investigation of hyperferritinemia that facilitates the investigation both in primary and inpatient care.

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

Background: Despite routine iron supplementation for pregnant women in South Africa, anaemia and iron deficiency (ID) in pregnancy remain a public health concern., Objective: To determine the associations between iron status and birth outcomes of pregnant women attending antenatal clinic at a regional hospital in Bloemfontein., Methods: In this cross-sectional study of 427 pregnant women, blood was taken to analyze biomarkers of anaemia (haemoglobin), iron status (ferritin and soluble transferrin receptor) and inflammation (C-reactive protein and α-1-acid glycoprotein). A questionnaire was used to collect information about birth outcomes (birth weight and gestational age at birth), HIV exposure, sociodemographics, iron supplement intake, and maternal dietary iron intake using a validated quantified food frequency questionnaire., Results: The median (Q 1 , Q 3 ) weeks of gestation of participants was 32 (26, 36) at enrolment. Anaemia, iron deficiency (ID), ID anaemia (IDA) and ID erythropoiesis (IDE) were present in 42%, 31%, 19% and 9.8% of participants, respectively. Median (Q 1 , Q 3 ) dietary and supplemental iron intake during pregnancy was 16.8 (12.7, 20.5) mg/d and 65 (65, 65) mg/d, respectively. The median (max-min) total iron intake (diet and supplements) was 81 (8.8-101.8) mg/d, with 88% of participants having a daily intake above the tolerable upper intake level of 45 mg/d. No significant associations of anaemia and iron status with low birth weight and prematurity were observed. However, infants born to participants in the third hemoglobin (Hb) quartile (Hb > 11.3-12.2 g/dL) had a shorter gestation by 1 week than those in the fourth Hb quartile (Hb > 12.2 g/dL) (p = 0.009). Compared to pregnant women without HIV, women with HIV had increased odds of being anaemic (OR:2.14, 95%CI: 1.41, 3.247), having ID (OR:2.19, 95%CI: 1.42, 3.37), IDA (OR:2.23, 95%CI: 1.36, 3.67), IDE (OR:2.22, 95%CI: 1.16, 4.22) and delivering prematurely (OR:2.39, 95%CI: 1.01, 5.64)., Conclusion: In conclusion, anaemia, ID, and IDA were prevalent in this sample of pregnant women, despite the reported intake of prescribed iron supplements, with HIV-infected participants more likely to be iron deficient and anaemic. Research focusing on the best formulation and dosage of iron supplementation to enhance iron absorption and status, and compliance to supplementation is recommended, especially for those living with HIV infection., (© 2024. The Author(s).)

Background: Interstitial lung disease (ILD) may complicate the course of systemic autoimmune rheumatic disease (SARD) and diagnostic biomarkers are needed. Krebs von den Lungen-6 (KL-6), ferritin (FER) and interleukin 6 (IL-6) have been involved in the ILD development. Our study aimed to compare KL-6, FER, IL-6 and soluble mesothelin-related peptide (SMRP) concentrations in a cohort of idiopathic and SARD-ILD., Methods: 3169 patients were enrolled in the "UK Biomarkers in Interstitial Lung Disease (UK-BILD) Study". We selected patients affected by SARD-ILD and idiopathic ILD (usual interstitial pneumonia-idiopathic pulmonary fibrosis and fibrotic non-specific interstitial pneumonia). Serum marker concentrations were measured through chemiluminescent assays (Fujirebio Europe, Ghent, Belgium)., Results: 1013 patients were selected for the study: 520 (51.3%) had idiopathic ILD and 493 (48.7%) SARD-ILD. Idiopathic ILD patients displayed higher KL-6 values than SARD-ILD (p = 0.0002). FER and SMRP, though within normal ranges, were significantly higher in idiopathic ILD (p<0.0001). Logistic regression showed good sensitivity (69.4%) and specificity (80.4%) selecting the variables FER and KL-6 concentrations, age and gender-male correlated with a diagnosis of idiopathic ILD., Conclusion: Our study showed the excellent diagnostic value of KL-6 for detecting ILD, which irrespective of the final diagnosis and extent of disease, is always elevated and is a reliable biomarker of lung fibrosis in various diseases, ranging from idiopathic to autoimmune forms. Our study proposed an ILD differentiation model including clinical background. In this context, combination of serum markers and clinical data, as seen in our cohort, may lead to a further improvement in diagnostic accuracy for ILD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 d’Alessandro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite advancements in diagnostic modalities, delineating the etiology of fever of unknown origin (FUO) remains a significant challenge for clinicians. Notably, cases with hematological malignancies often have a poor prognosis due to delayed diagnosis. This study investigated the potential of readily obtainable laboratory markers to differentiate hematological causes from other etiologies during the early stages of FUO. A retrospective analysis was conducted on the medical records of 100 patients who fulfilled the modified FUO criteria between January 2010 and April 2023. Hematological etiologies were identified in 26 of the 100 patients. Peripheral blood neutrophil, lymphocyte, platelet counts, and the systemic immune inflammation (SII) index, were significantly lower in the hematological group compared to the non-hematological group. Conversely, serum ferritin levels were demonstrably higher in the hematological group. ROC analysis identified a neutrophil-to-ferritin ratio (NFR) cutoff value of < 8.53 as optimal for predicting hematological etiology. Subsequent multivariate analysis demonstrated that the NFR was the sole independent predictor of hematological etiology (p = 0.013).This study proposes a novel approach for early diagnosis of a potentially life-threatening subset of FUO patients. The NFR presents as an inexpensive and readily available marker for predicting hematological etiology in FUO cases., (© 2024. The Author(s).)

Objective: To investigate the value of serum ferritin, folic acid and vitamin B 12 in the treatment of multiple myeloma (MM) with bortezomib combined with chemotherapy., Methods: Clinical data of 40 MM patients admitted to our hospital from January 2020 to August 2022 and 40 hematology outpatients during the same period were reviewed. All MM patients were treated with bortezomib combined with chemotherapy. The diagnostic efficacy of serum ferritin, folic acid and vitamin B 12 on MM was analyzed by ROC curve. The changes of serum ferritin, folic acid and vitamin B 12 in MM patients before and after treatment were compared. According to the mean values of serum ferritin, folic acid and vitamin B 12 , patients were divided into high and low expression groups, and the survival of patients between the groups was compared., Results: Before treatment, the levels of serum ferritin and vitamin B 12 in MM patients were significantly higher than those in control group, while folic acid was lower (all P <0.001). The area under the curve (AUC) of MM patients diagnosed with ferritin, folic acid and vitamin B 12 were 0.928, 0.843 and 0.867, the specificity was 100%, 67.50% and 72.50%, and the sensitivity was 80.00%, 95.00% and 87.50%, respectively. After 4 cycles of chemotherapy, there were 9 cases of complete remission (CR), 19 cases of very good partial remission (VGPR), 6 cases of PR, 4 cases of stable disease (SD) and 2 cases of progression disease (PD) in 40 MM patients. In CR group, ferritin and vitamin B 12 decreased but folic acid increased after treatment compared with before treatment (all P < 0.05). The overall survival (OS) rates of patients in low expression group of ferritin and vitamin B 12 were significantly higher than those in high expression group (both P < 0.01). The OS rate of patients in high expression group of folic acid was significantly higher than that in low expression group ( P < 0.01). Cox regression analysis showed that ferritin was an independent prognostic factor for MM patients ( HR =8.850, 95% CI : 2.267-34.553, P =0.002)., Conclusion: Serum ferritin, folic acid and vitamin B 12 have some auxiliary value in the diagnosis and efficacy evaluation of MM, and ferritin is an independent prognostic factor for MM.

Objective: To determine the prevalence of iron deficiency among primary school students in an urban setting., Methods: The descriptive, cross-sectional study was conducted from January to April 2019 in Mosul, Iraq, after approval from the ethics review committee of the College of Medicine, Nineveh University, Iraq, and comprised students aged 6-12 years who were part of the 2018-19 academic year at 4 public primary schools located along the two banks of Tigris River. Serum ferritin was measured in all the participants. Data wa analysed using Minitab 20., Results: Of the 827 subjects, 439(53%) were girls and 388(47%) were boys. The overall mean age was 8.5±0.057 years, with 558(67.5%) aged <10 years. The mean serum ferritin level was 8.05±6.43ng/ml, and 173(20.92%) subjects were found to iron-deficient. Among the iron-deficient students, 87(50.29%) had iron deficiency anaemia and 86(49.71%) had non-anaemic iron deficiency. Age and gender were significantly different between students with anaemic and non-anaemic iron deficiency (p<0.05). Within boys, significant difference was also noted in terms of body mass index-for-age values (p<0.05)., Conclusions: One-fifth of the students were found to have iron deficiency. Plans to control iron deficiency among young children are essential.

Objective: To determine whether tocilizumab improved outcomes of patients hospitalised with severe coronavirus disease-2019 cytokine storm syndrome., Methods: The case-control study was conducted at Al-Yarmouk Teaching Hospital, Baghdad, and Al Shatra General Hospital, Thi Qar, Iraq, from September 2020 to March 2021, and comprised patients with severe acquired respiratory syndrome-corona virus-2 pneumonia who were not candidates for mechanical ventilation and received a single-dose intravenous infusion of tocilizumab 8mg/kg in group A. The outcomes were compared with patients in group B who received only standard care. Data was analysed using SPSS 26., Results: Of the 60 patients, 30(50%) were in group A; 22(73.3%) males and 8(26.7%) females with mean age 56.63±10.92 years. There were 30(50%) patients in control group B; 24(80%) males and 6(20%) females with mean age 54.8±6.18 (p>0.05). Group A showed significant changes compared to group B in the levels of interleukin-6, serum ferritin, D-dimer, procalcitonin, lymphocytes count and oxygen saturation (p<0.05). Mortality rate was not significantly different between the groups (p>0.05)., Conclusions: Majority of the acute phase inflammatory markers were reduced significantly by treatment with tocilizumab.

Objective: To assess the role of inflammatory markers ferritin and C- reactive protein as indicators of preeclampsia severity., Methods: The case-control study was conducted at Al-Yarmouk Teaching Hospital, Baghdad, Iraq, from November 2021 to May 2022, and comprised pregnant women from the obstetrics ward and outpatient clinics aged 16-40 years having a viable singleton pregnancy and gestational age >32 weeks. They were divided into severe preeclampsia group A, non-severe preeclampsia group B and control group C. Serum ferritin and C-reactive protein levels were measured for all the subjects, and compared. Data was analysed using SPSS 26., Results: Of the 87 pregnant women, 27(31%) were in group A with mean age 29.76±7.53 years and mean gestational age 35.63±1.92 weeks, 29(33.33%) were in group B with mean age 26.83±6.30 years and mean gestational age 36.24±1.72 weeks, and 31(35.63%) were in group C with mean age 26.00±5.73 years and mean gestational age 36.52±1.61 weeks. Ferritin levels in patient groups were significantly higher than in the control group (p<0.05), but it was not significantly different between the patient groups (p>0.05). C-reactive protein levels in the patient groups were significantly higher than in the control group (p<0.05), and they were also significantly higher in group A than in group B (p<0.05). At a cut-off value >101.8 ferritin had sensitivity 92.59% but specificity 20.69%, whereas C- reactive protein at a cut-off value >17.1 had sensitivity 66.67% but specificity 75.86%., Conclusions: Serum C- reactive protein level was significantly associated with severity of preeclampsia with an acceptable grade of discriminative ability between severe preeclampsia and non-severe preeclampsia patients.

A characteristic feature of the cytokine storm in coronavirus disease 2019 (COVID-19) is the dramatic elevation of serum interleukin 10 (IL-10). This may be a negative feedback mechanism to suppress inflammation. However, this IL-10 elevation may contribute to COVID-19 severity. In our study, we aimed to evaluate the effect of serum IL-10 level on patients' clinical outcome and the incidence of post-COVID19 pulmonary fibrosis. This was a prospective observational study, included 100 patients, confirmed to have COVID-19, Of these, 50 patients had COVID-19 without evidence of pneumonia in computed tomography (CT) scans (group I) and the other 50 patients had COVID-19 pneumonia (group II). Our results showed a significant increase in serum ferritin level in patients with COVID pneumonia. However, no difference was found in serum C-reactive protein (CRP) nor D-Dimer between both groups. There was a statistically significant increase in serum IL-10 in patients with COVID pneumonia compared with COVID patients without pneumonia (p < 0.001). Fibrosis was developed in 35 patients (70%) with COVID pneumonia after 3 months and 4 of them died, however, all patients without pneumonia survived. Among age, serum IL-10, aspartate aminotransferase (AST), alanine transaminase (ALT), elevated serum IL-10 was found to be an independent predictor of pneumonia (p=0.32). However, there was no significant effect for IL-10 on patients' clinical outcome. There was a statistically significant correlation between serum IL-10 levels and oxygen (O2) demand, CRP and D-Dimer (p= 0.015, p=0.034 and p=0.042, respectively). The higher the level of IL-10 the less fibrosis detected in follow up CT scans (p=0.038). In conclusion, even though IL-10 was significantly associated with disease severity (higher in pneumonia), elevated serum Il-10 has an independent role in decreasing the incidence of post-COVID-19 pulmonary fibrosis., (Copyright© by the Egyptian Association of Immunologists.)

Objective: To evaluate the relationship between homocysteine levels and anti-mullerian hormone (AMH) levels, a biomarker of ovarian reserve, and the effect of high homocysteine levels on ovarian reserve in subfertile women., Study Design: Observational case-control study. Place and Duration of the Study: Samsun Training and Research Hospital, Samsun, Turkiye, from October to December 2023., Methodology: Seventy-nine subfertile women and 35 healthy fertile women were included in this study. AMH, homocysteine, thyroid stimulating hormone (TSH), free T3 (fT3), free T4 (fT4), iron, and ferritin levels of subfertile and fertile women were compared. Logistic regression, receiver operating characteristic, and Kaplan-Meier analyses were performed for homocysteine levels., Results: AMH, fT4, iron, and ferritin levels were lower in subfertile women than in fertile women (p <0.001). Homocysteine and TSH levels were higher in subfertile women than in fertile women (p <0.001). The sensitivity for homocysteine levels was 94.90% and the specificity was 94.30%. In the Kaplan-Meier analysis, homocysteine levels of 12.90 μmol/L and above were found to be risky in terms of fertility. Homocysteine levels, AMH, and ferritin levels were negatively correlated and TSH levels were positively correlated in subfertile women (p <0.001). However, these correlations were not observed in fertile women (p >0.05)., Conclusion: High homocysteine levels can be considered as a risk factor affecting ovarian reserve in subfertile women., Key Words: Anti-mullerian hormone, Female subfertility, Homocysteine, Hyperhomocysteinaemia, Ovarian reserve.

Background: Serum ferritin is a sensitive inflammatory biomarker reflecting cell damage and oxidative stress in inflammatory rheumatic diseases. The use of ferritin for assessment of systemic sclerosis (SSc) activity, severity, and prognosis has not been fully elucidated., Objectives: To assess the correlation between serum ferritin levels and SSc disease parameters, complications, and outcome., Methods: Demographic, clinical, and laboratory data, including blood levels of ferritin, were collected from files of patients with SSc who were treated at the Rheumatology Institute at Rambam Health Care Campus from January 2004 to July 2021. The study compared SSc patients with elevated levels of ferritin to those with normal levels., Results: We extracted data of 241 SSc patients (80% female, 60% with diffuse SSc, mean age 54 ± 15.4 years, mean disease duration 6.8 ± 4.5 years). During follow-up, 39% died. Elevated ferritin levels positively correlated with male sex; short disease duration; lung, heart, and kidney involvement; higher modified Rodnan skin score; anemia; elevated levels of creatinine kinase, C-reactive protein, creatinine, and troponin; reduced pulmonary function tests (forced vital capacity and diffusion capacity of the lung for carbon monoxide); and left ventricular ejection fraction. There were no correlations between ferritin levels and pulmonary hypertension or gastrointestinal involvement. Levels of ferritin negatively correlated with anti-centromere antibodies., Conclusions: In SSc, ferritin can serve as a marker for ongoing systemic inflammation and prognosis, particularly in patients with lung and heart involvement. Further studies on serial ferritin measurement in the management of SSc patients are warranted.

Competing Interests: MT is the director of SKML, a non-profit organisation that provides external quality assurance schemes that include ferritin, with method grouping acording to metrological traceability. SKML is paid by participants and has no financial relationship with any commercial organisation related to ferritin assays. SKML's only interest in this Correspondence is in expressing its external quality assessment judgement of ferritin that is professional objective judgement based on metrological traceability from SKML. All other authors declare no competing interests.

The COVID-19 pandemic has affected the global health system and economies largely. Therefore, knowledge about the clinical and laboratory profiles of patients with COVID-19 would help in the management and prognosis of the disease. The immunological and hematological indices have emerged as critical determinants for the severity of the disease and the prognosis; however, association with COVID-19 is clouded. The present study is aimed to characterize the immunological and hematological profiles of patients with COVID-19 in correlation with the disease severity. The study included 1,019 polymerase chain reaction (PCR)-confirmed patients with COVID-19 who were classified into serious and nonserious groups, considering severity criteria. Clinical laboratory investigations included hematological, biochemical, and immunological parameters regarding leukocyte counts, hemoglobin levels, and inflammatory markers. Our analysis of immunological and hematological differences between serious and nonserious patients with COVID-19 indicates that serious cases reflected elevated levels of pro-inflammatory markers such as lactate dehydrogenase, C-reactive protein (CRP), D-dimer, and ferritin, representing immune system dysregulation and systemic inflammation. Furthermore, in serious cases, discrepancies had also been noticed for many hematological parameters than nonserious ones, which also contained leukocyte count and hemoglobin level. Additionally, the CRP, D-dimer, blood urea nitrogen, alanine transaminase, and albumin levels could be independent predictors of COVID-19 severity by multivariate logistic regression analysis. Cutoff values for these biomarkers were defined by receiver operating characteristic curve analysis defining optimal parameters for the risk stratification and prognostication. The current investigation provides a comprehensive understanding of immunological and hematological correlation with COVID-19 severity, refining clinical decision-making and therapeutic interventions to improve patient outcomes.

The COVID-19 pandemic has emerged as a major global health crisis. Vitamin D, a crucial fat-soluble vitamin, has been recommended for COVID-19 patients, though evidence of its effectiveness is inconsistent. This systematic literature review and meta-analysis aimed to evaluate the impact of vitamin D supplementation on COVID-19-related outcomes. A comprehensive search was conducted across PubMed, Scopus, Web of Science, Embase, and Cochrane databases. Primary outcomes included mortality and hospital length of stay, while secondary outcomes encompassed C-reactive protein (CRP), ferritin, D-dimer, hemoglobin (Hb) concentrations, and lymphocyte, neutrophil, and platelet counts. Data analysis was performed using Stata™ Version 14. A total of 16 trials were analyzed. The meta-analysis revealed that vitamin D supplementation significantly reduced hospital length of stay (mean difference = -1.16; 95% confidence interval [CI]: -2.23, -0.09; p = .033) with significant heterogeneity (I 2  = 69.2%, p = .002). Subgroup analysis showed a more pronounced reduction in studies with vitamin D dosages ≤10 000 international units (IU) (mean difference = -1.27; 95% CI: -1.96, -0.57; p < .001) and in patients over 60 years old (mean difference = -1.84; 95% CI: -2.53, -1.14; p < .001). Additionally, vitamin D significantly reduced CRP concentrations in older adults (>60 years) (mean difference = -1.13; 95% CI: -2.07, -0.18; p = .019). No significant changes were found in ferritin, D-dimer, Hb concentrations, or in lymphocyte, neutrophil, and platelet counts (p > .05). In conclusion, while vitamin D supplementation did not significantly affect most COVID-19-related biomarkers, however, it reduces the length of hospital stay., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Most of the thalassemic children of Bangladesh are receiving repeated blood transfusion. But they do not receive chelation therapy due to financial constraints. As a result, iron overload occurs in various organs of these children. Extra iron that is loaded in thyroid gland causes thyroid dysfunction. This study was undertaken to evaluate thyroid status in children with transfusion dependent Thalassemia patient. This cross-sectional analytical study was conducted in the Department of Pediatrics, Mymensingh Medical College Hospital, Bangladesh from September 2016 to April 2018. Children having thalassemia diagnosed by Hb electrophoresis, aged 3-12 years of both sexes were included as study group. Children of same age and sex admitted in indoor of Mymensingh Medical College Hospital with minor illness and without thalassemia were taken as comparison group. Purposive Sampling technique was applied. Serum FT₄, TSH and ferritin level were estimated in all children. Data analysis was done with Statistical Package for Social Science (SPSS) version 21.0. A total of 60 patients were enrolled as study group and another 60 patients were compared as comparison group. Mean ages of study group was 7.88±2.55 years and comparison group were 7.22±2.48 years. The mean pre-transfusion hemoglobin, serum ferritin, serum FT₄ and serum TSH level were found 6.23±0.60 gm/dl, 2658.33±879.39 ng/ml, 15.14±4.40 fmol/mL, 4.29±4.60 μIU/mL respectively in study group. The mean serum FT₄ was found significantly lower and mean serum TSH was significantly higher in thalassemic children in comparison to non-thalassemic children (p= <0.05). Frequency of subclinical hypothyroidism was found significantly higher in study group (25.0%) compared to comparison group (3.3%) (p=0.001). Mean serum ferritin level was found significantly higher in hypothyroid cases. Mean FT₄ level was significantly lower and mean TSH level was significantly higher in hypothyroid thalassemic patients (p= <0.001). Significant positive correlation between serum ferritin level and serum TSH level was found. Higher serum ferritin level was found significantly associated with the development of hypothyroidism in thalassemic patients.

Stroke is one of the major causes of morbidity and mortality throughout the world. Research is going on to find out the factors which are associated with the severity of acute ischemic stroke. One of the factors which has gained interest in the field of research in recent time is serum ferritin. Serum ferritin is an acute phase reactant. It is recently under research as a marker of severity and prognosis of acute ischemic stroke. The aim of this study was to assess the relation of serum ferritin level with the severity of acute ischemic stroke. This cross-sectional study was conducted in the Department of Medicine in Mymensingh Medical College Hospital, Bangladesh from June 2020 to March 2023. In this study, 323 patients with acute ischemic stroke were enrolled. The severity of neurological disability was evaluated in all participants using National Institute of Health stroke scale (NIHSS) within 48 hours of onset of stroke. Blood was taken for estimation of serum ferritin levels within 48 hours of admission. In this study, mean serum ferritin level was 208.3±161.1 ng/ml in patients with acute ischemic stroke. The study showed most of the participants with high serum ferritin level had severe stroke (n=57, 77.0%; p<0.001). A statistically significant correlation was found between NIHSS and serum ferritin levels in acute ischemic stroke patients (r=0.71). This study revealed that serum ferritin level is associated with severity of neurological disability among patients with acute ischemic stroke. Further studies are required to establish the role of serum ferritin as a prognostic marker of acute ischemic stroke.

Background: Overweight/obesity and iron deficiency (ID) are highly prevalent in women of reproductive age (WRA), impacting on women's health. Obesity is a risk factor for nutritional deficiencies but its association with ID is unclear., Objectives: To determine the association between adiposity and markers of iron status and ID prevalence in WRA., Methods: This cross-sectional study analyzed the National Diet and Nutrition Survey (2008-2019) data, focusing on women aged 18-49 y with body mass index (BMI) ≥18.5 kg/m 2 . Prevalence of anemia, iron deficiency anemia (IDA), and ID were analyzed. Ferritin was adjusted for C-reactive protein. Iron status was assessed across high and low BMI, waist circumference (WC), waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR). χ 2 , linear and logistic regressions were performed adjusting for covariates., Results: Among 1098 WRA, 496 normal weight and 602 overweight/obesity, prevalence rates were: anemia 9.2% and IDA 6.8%. Anemia was more prevalent in those with higher WHtR and WHR (11.9% compared with 5.9% and 16.7% compared with 6.5%, both P < 0.001). WRA with increased WC, WHtR, and WHR had higher IDA prevalence than those with lower adiposity (8.5% compared with 4.3%, P = 0.005; 9.4% compared with 3.3%, P < 0.001; 12.1% compared with 4.9%, P < 0.001). ID prevalence was 49.7% (ferritin cutoff 30 μg/L) and 19.6% (ferritin cutoff 15 μg/L), showing similar rates across adiposity groups. ID prevalence defined by soluble transferrin receptor (sTfR) was higher in women with increased WHR (P = 0.001). Higher WHR predicted ID categorized by sTfR (adjusted odds ratio [aOR]: 2.104, P = 0.004), and WHtR and WHR predicted anemia and IDA (anemia: WHtR aOR: 2.006, P = 0.036; WHR aOR: 4.489, P < 0.001 and IDA: WHtR aOR: 2.942, P = 0.012; WHR aOR: 4.142, P < 0.001)., Conclusions: At least 1 in 5 WRA in the UK are iron deficient, highlighting the need to revise current policies. Greater central adiposity was strongly associated with impaired iron status and the development of anemia, IDA, and ID., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Glyphosate and glyphosate-based herbicides (GBH), widely used globally, were initially considered harmless to humans. Experimental studies have suggested that these substances can disrupt iron homeostasis by interfering with iron uptake or triggering inflammatory responses. However, their potential impact on human iron homeostasis remains underexplored., Approach and Results: We analyzed data from 5812 participants aged three and older from the 2013 to 2018 NHANES. We investigated the relationships between urinary glyphosate levels, oral iron intake, and markers of iron homeostasis, including serum iron, unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), transferrin saturation, ferritin, and transferrin receptor. Higher urinary glyphosate levels were positively associated with oral iron intake (β = 1.310, S.E. = 0.382, P = 0.001). A one-unit increase in the natural logarithm (ln)-glyphosate was associated with lower serum iron (β = - 4.236, 95 % CI = - 6.432 to - 2.039, P < 0.001) and ferritin (β = - 9.994, 95 % CI = - 17.342 to - 2.647, P = 0.009), and higher UIBC (β = 5.431, 95 % CI = 1.061-9.800, P = 0.018) and transferrin receptor levels (β = 0.139, 95 % CI = 0.015-0.263, P = 0.029). Increasing glyphosate exposure was associated with significant decreases in serum iron and ferritin across exposure quintiles (trend P-values = 0.003 and 0.018, respectively)., Conclusions: Higher glyphosate exposure is associated with reduced iron availability, suggesting potential disruptions in iron absorption. These findings underscore the need for further research into the health implications of glyphosate exposure on iron homeostasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ferritin is an iron deposition protein and a commonly ordered clinical test. While high levels may signify iron deposition, the majority are due to metabolic, inflammatory, infectious, and malignant disorders. The association between ferritin elevations < 1000 μg/L and long-term mortality is well demonstrated. The association between extreme ferritin elevations, namely ferritin levels over 10,000 μg/L, and short-term mortality, as well as predictors of mortality, has not been defined., Methodology: A retrospective chart study was designed in an academic hospital to analyze the clinical, laboratory, and mortality characteristics of patients whose ferritin is over 10,000 μg/L. Patients from 2012 to 2023 in a large academic center's electronic medical records were analyzed. Demographics, underlying disorders, laboratory values, mortality status, and days to mortality were acquired. Multivariate logistic regression analysis was used to define predictors of mortality. The Kaplan-Meier survival curve was used to analyze survival., Results: Sixty-seven patients were identified to have ferritin levels over 10,000 μg/L. The most common underlying disorders were infectious diseases and malignancies. Predictors of mortality in the multivariate logistic regression model were also infectious disease (odds ratio (OR) = 5.35), and malignancy (OR = 6.56), as well as age (OR = 1.05). The area under the curve of the model was .86. 1-year mortality was 62%. Of the patients who died, median survival was 5 days; 30- and 90-day mortality were 80% and 92%, respectively., Discussion: Extreme hyperferritinemia is associated with high short-term mortality. Ferritin can be used as a marker of poor prognosis, particularly among patients with infection and malignancy., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Introduction: The rapid increase in obesity and related problems has heightened the importance of obesity and metabolic surgery, resulting in a continuing search for the ideal surgical method. This study aimed to compare the effectiveness of Roux-en-Y gastric bypass (RYGB), which is the gold standard method, and the relatively newer method of single anastomosis sleeve ileal (SASI) bypass., Methods: The medical records of patients who underwent RYGB and SASI bypass were reviewed and compared regarding excess weight loss (EWL) and HgA1c, fasting glucose, serum iron, ferritin, hemoglobin (Hgb), and vitamin B12 levels., Results: The body mass index was significantly lower (p = 0.003), and the %EWL was significantly higher (p = 0.023) at 6 months postoperative in patients who underwent SASI bypass. Both groups had similar results at the other follow-up visits. The mean HgA1c levels at the 6- and 12-month follow-up visits were significantly lower in SASI patients (p = 0.037 and p = 0.012, respectively). At the 24-month follow-up, no difference was detected in HgA1c levels between the groups (p = 0.476). In patients who underwent RYGB, ferritin (p < 0.001), plasma iron (p = 0.001), and Hgb levels (p = 0.001) were significantly lower at 12, 24, and 12 months postoperatively, respectively., Conclusion: SASI bypass is effective and comparable to RYGB in terms of EWL and metabolic control and has the advantage of not producing excluded segments and reducing nutritional deficiencies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Post-operative anaemia is linked to iron deficiency. We investigated the prognostic value of post-operative iron biomarkers in colorectal cancer (CRC)., Methods: Ferritin, transferrin, iron, and transferrin saturation (TS%) were measured from blood collected at a single time-point post-surgery in 2769 CRC patients. Associations between iron biomarkers with cancer-specific survival (CSS) and overall survival (OS) were assessed using Cox regression with hazard ratios (HR), stratified by post-operative time of blood collection (<1-month/≥1-month)., Results: After a median follow-up of 9.5 years, 52.6% of patients had died. For iron biomarkers assessed <1-month post-surgery, higher compared to normal TS% was associated with shorter CSS (HR [95% CI] = 2.36 [1.25-4.46]), and higher iron levels with better OS (upper vs. median tertile: HR [95% CI] = 0.79 [0.65-0.97]). When assessed ≥1-month post-surgery, elevated ferritin was associated with poor CSS (high vs. normal: HR [95% CI] = 1.44 [1.10-1.87]), and low TS% with worse CSS (low vs. normal: HR [95% CI] = 1.60 [1.24-2.06]). Similar but weaker associations were observed for OS., Conclusion: Monitoring of serum ferritin and TS% beyond 1-month post-surgery may be relevant for risk stratification of patients with operable CRC. Future studies should validate our findings., (© 2024. The Author(s).)

Introduction: The aim of this study was to investigate the value of point shear-wave elastography (pSWE) in the measurement of iron overload in the liver and other visceral organs in patients with beta thalassemia major (BTM)., Materials and Methods: The study included 103 patients diagnosed with BTM who were referred to our clinic for cardiac and liver T2* measurement and a control group of 120 age- and gender-matched healthy volunteers. Cardiac and hepatic T2* measurements were performed in the patient group. Hepatic, pancreatic, splenic, and renal pSWE values were measured in both groups. The pSWE values were compared between the two groups. In the patient group, correlations between pSWE values, cardiac-hepatic T2* values and hepatic size, patient age, and serum ferritin levels were analyzed., Results: Hepatic, pancreatic, splenic, and renal pSWE values were significantly higher in the patient group compared to the control group (p ≤ 0.001, < 0.001, 0.014, 0.026, respectively). In the patient group, hepatic pSWE values established a significant correlation with cardiac T2* values, liver size-T2*, pancreatic pSWE values, serum ferritin levels, and age (p = 0.006, < 0.001, 0.001, 0.042, 0.001, 0.032, respectively). In the ROC analysis, the area under the ROC curve was 0.807 for hepatic pSWE in the discrimination of thalassemia patients and healthy controls, and the cut-off value was 1.42, which gave a sensitivity and specificity of 75.7% and 75%, respectively. CONCLUSıON: Point shear-wave elastography can be a useful technique in the clinical measurement of iron overload in the liver, pancreas, spleen, and kidney., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Introduction: Whole blood donors are at increased risk for iron deficiency (ID). ID anemia is associated with several symptoms, such as fatigue, cognitive dysfunction, pica, and restless leg syndrome (RLS). However, it is unclear if these symptoms also occur when a donor has developed ID without anemia. This study aims to determine whether non-anemic ID (NAID) is associated with the occurrence of ID-related symptoms., Study Designs and Methods: We combined data from three studies in whole blood donors (i.e., Donor Insight-III, FIND'EM, and FORTE) to create a substantial sample size (N = 12,143). The self-reported occurrence and severity of ID-related symptoms, such as physical and mental health, fatigue, cognitive functioning, pica, and RLS, was measured using validated questionnaires. Associations were studied using logistic regression modeling with ID-related symptoms derived from the questionnaires as the dependent variable and ferritin level group (0-15 μg/L, 15-30 μg/L, and >30 μg/L) as explanatory variable., Results: After applying inclusion and exclusion criteria, 9829 donors were eligible for analysis. In the models corrected for age, body mass index, Hb level, and cohort, only fatigue was shown to be associated with ferritin levels in men, showing lower odds (OR 1.41, 95% CI 1.11-1.79) for fatigue with higher ferritin levels., Conclusion: In these studies, NAID was only associated with self-reported fatigue in male donors. Although selection bias may have led to underestimated associations, ferritin measurements in donors should be primarily considered as a measure to prevent anemia, rather than to prevent or mitigate NAID-related symptoms., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

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

Aims: The mortality rate for -COVID-19 infection varies significantly depending on age and comorbidities but remains high in hospitalized patients overall. Several retrospective studies have identified patients with end-stage kidney disease (ESKD) to be at increased risk. The objective of this study was to study in-hospital outcomes of ESKD patients at an academic medical center and identify characteristics that place them at a higher risk for in-hospital mortality., Materials and Methods: A retrospective chart review was conducted including adult patients (≥ 18 years old) admitted to Loma Linda Medical Center for COVID-19 infection with a previous diagnosis of ESKD. Patients with prior kidney transplants were excluded. The main outcome of this study was the rate of in-hospital mortality., Results: 21 of the 91 patients died with a mortality rate of 23%. Age, D-dimer > 0.4 µg/mL, ejection fraction less than 50%, and ferritin > 300 ng/mL were predictors for mortality in unadjusted univariate analysis. Adjusted multivariable analysis demonstrated that only an ejection fraction of less than 50% was associated with increased mortality risk., Conclusion: Cardiovascular disease is the leading cause of mortality for ESKD patients and also places them at increased risk of mortality in the setting of severe COVID-19 infection.

Objectives: Animal studies have suggested that dietary iron deficiency (ID) negatively affects dopamine (DA) synthesis and re-uptake, which in turn negatively affects memory and cognition. This study was intended to assess whether the pattern electroretinogram (pattern ERG) could be used as an indirect measure of DA in college-age women with and without ID by determining the extent to which features of the ERG were sensitive to iron status and were related to other indirect measures of DA., Methods: The pattern ERG was measured in 21 iron deficient non-anemic (IDNA) and 21 iron sufficient (IS) women, who also performed a contrast detection and probabilistic selection task, both with concurrent electroencephalography (EEG). Both spontaneous and task-related blink rates were also measured., Results: The implicit times of the A- and B-waves were significantly longer for the IDNA than for the IS women. Both the amplitudes and implicit times of the A- and B-waves were significantly correlated with levels of serum ferritin (sFt). Only the amplitude of the A-wave was correlated with spontaneous blink rate. It was possible to accurately identify a woman's iron status solely on the basis of the implicit time of the B-wave. Finally, the implicit times of the ERG features mediated the relationship between iron levels and accuracy in the probabilistic selection task., Conclusions: Results suggest the utility of the pattern ERG in testing the hypothesis that iron deficiency affects DA levels in humans and that this may be one of the mechanisms by which iron deficiency negatively affects cognition.

Objectives: To investigate characteristics and outcomes of critically ill cancer patients with marked hyperferritinemia., Methods: A single-center retrospective analysis comprising cancer patients with a ferritin level >10.000 μg/L treated in the intensive care unit (ICU) between 2012 and 2022 was conducted., Results: A total of 117 patients were included in the analysis. The median age was 59 years (range: 15-86 years). Females accounted for 48% of cases. 90% of patients had a hematologic malignancy. The median maximum ferritin level was 27.349 μg/L (range: 10.300-426.073 μg/L). The diagnostic criteria of septic shock were fulfilled in 51% of cases; 31% of patients had hemophagocytic lymphohistiocytosis (HLH) according to the HLH-2004 criteria. Mechanical ventilation, renal replacement therapy and the use of vasopressors were necessary in 59%, 35% and 70% of cases, respectively. The ICU, hospital, 90-day and 1-year survival rates were 33.3%, 23.1%, 23.7% and 11.7%. Patients with septic shock had a worse survival than those without septic shock (p = .001); the survival of patients who fulfilled the HLH-2004 criteria did not differ from those who did not (p = .88)., Conclusion: Critically ill cancer patients with marked hyperferritinemia have poor outcomes. The present data may help to make informed decisions for this patient group., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Preterm infants born at less than 32 weeks of gestation are at higher risk of low total iron stores (iron deficiency). Serum ferritin is used as a valid total iron stores and iron deficiency biomarker, usually as a combination of ferritin and red blood cell counts., Methods: Serum hepcidin and ferritin values and red blood cell counts were obtained from 37 of 40 included premature infants born at less than 32 weeks of gestation at risk of iron deficiency. The first sample was obtained in the first week of life, and the second at transfer from the Neonatal intensive care unit to the maternity ward, when serum ferritin level below 25 µg/L has been defined as very low total iron stores (iron deficiency)., Results: Ferritin median levels decreased from a median value of 152 µg/L at the first measurement to 54 µg/L at the second measurement. Hepcidin median levels also decreased from 30.1 µg/L to 2.1 µg/L. We found a positive and statistically significant correlation between levels of ferritin and hepcidin at both measurements (r=0.57; P<0.001 and r=0.72; P<0.001, respectively). Compared to serum hepcidin, ferritin at the first measurement has not statistically significant higher power in predicting children with iron deficiency before discharge from the hospital., Conclusions: We found a correlation between ferritin and hepcidin levels. Nevertheless, hepcidin does not have a worse power in predicting children with iron deficiency compared to ferritin.

Ferritin (Ftn), a globular protein, sequesters 4500 atoms of iron per molecule. Elevated serum Ftn levels (hyperferritinemia) is an indicator of iron homeostasis disorders. We present the results of an observational study involving 17 patients with hyperferritinemia unrelated to hereditary hemochromatosis (HH). All participants received treatment with 200 mg of bovine lactoferrin (bLf) once ( n  = 14) or twice ( n  = 3) a day before meals. The patients, treated with 200 mg/day of bLf, exhibited a significant increase in red blood cells (+10%, p  < 0.001), hemoglobin (+4%, p  < 0.001), and hematocrit (+15%, p  = 0.004), accompanied by a significant reduction in serum Ftn levels (-52%, p  < 0.001), C-reactive protein (CRP) (-85.0%, p  < 0.001), and D-dimers (-19%, p  < 0.001). Among the three patients treated with 400 mg/day of bLf, two had effects similar to those of patients bLf-treated with 200 mg/day and one experienced a strong reduction of Ftn, CRP, and erythrocyte sedimentation rate (from -97% to -75%). The decrease in serum Ftn levels due to bLf treatment was largely independent of gender ( p  = 0.78), age ( p  = 0.66), baseline symptoms ( p  = 0.20), and concomitant acute ( p  = 0.34) and chronic ( p  = 0.53) infections. Although this observational pilot study yields positive effects in patients with hyperferritinemia unrelated to HH treated with bLf, a larger sample size is needed for conclusive results., Competing Interests: Anna Maria Costanzo is an employee of Pharmaguida s.r.l. The other authors declare there are no competing interests.

Background and Objectives: Acute pancreatitis (AP) carries the risk of subsequent nutritional deficiencies. The prevalence of these deficiencies following a single episode of AP in children is unknown. We aimed to determine prevalence of anthropometric and laboratory-based measures of nutritional status in children following their first (index) admission for AP., Methods: Prospective observational cohort study of patients ≤21 years of age with first episode of confirmed AP. Anthropometric and laboratory values were obtained at time of AP onset and at follow up time points of 3 and 12 months (m) post AP. AP attack was classified as either: mild, moderately severe or severe (which were combined in one group (SAP))., Results: 181 patients met criteria and were followed prospectively with 52% male, a median age of 13.7 years (IQR 9.4-16.0) and median Body Mass Index (BMI) Z-score of 0.6 (IQR -0.5, 1.6). Most patients had mild AP (140, 77%), with 23% meeting criteria for moderate or severe (41/181). 6 (3%) had diabetes mellitus (DM) predating AP and were excluded from further analysis. BMI Z-score remained stable during the follow up period. 13% of patients developed pre-DM or DM at 3m or 12m. Nearly one third of patients had low ferritin at 3m (29%) or 12m (29%). At 12m, 8% of patients had Vitamin A deficiency. 6% of patients had low Vitamin E levels at 3m and 5% at 12m. Over half of patients at both 3m and 12m had 25 OH Vitamin D insufficiency or deficiency (56% and 56%). Prolonged International Normalized Ratio (INR) (>1.3) was seen in 9% of patients at 12m. Very low albumin (<3.5 g/dL) was found in 24% of patients at 3m and 18% at 12m (Table 1). Patients with very low albumin at 3m were younger (median 10.7 vs. 14.2 years, p = 0.04), however sex, BMI Z-score and AP severity were not associated with albumin level. Although BMI Z-score did not differ between the groups, those with SAP had a significant decrease in BMI Z-score from first attack compared to mild AP at 3m (-0.4 vs. 0.0, p = 0.0002, Figure 2). At 3m, Vitamin E deficiency in SAP versus mild AP was found in 20% vs 2% (p = 0.04) and SAP had a lower median hematocrit (35.8 vs. 37.6, p = 0.046). There were no other laboratory significant differences at 3m in mild versus SAP groups. At 12m, those with SAP were more likely to have pre-DM or DM compared to mild AP (31% vs. 7%, p = 0.002). No other significant laboratory differences occurred at 12m., Conclusions: After the first AP attack patients experience nutritional deficiencies, including ferritin, all fat-soluble vitamins, and low albumin. SAP is associated with a decrease in BMI Z-score, increased prevalence of vitamin E deficiency at 3m, and an increase in pre-diabetes and diabetes at 12m. Serial monitoring of vitamin and mineral values post AP is warranted and further prospective studies are needed., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aimed to compare the anthropometry and body composition of vegetarian and omnivorous adults living in Portugal, while exploring nutritional and health parameters underlying observed differences., Methods: 425 omnivorous (OMNI), lacto-ovo-vegetarian (LOV), or vegan (VEG) healthy adults were recruited. Anthropometry was measured, and bioelectrical impedance analysis was performed. Participants answered food frequency, sociodemographic, and lifestyle questionnaires. Serum iron, ferritin, and CRP were quantified by spectrophotometry, and serum B12 vitamin and homocysteine were quantified by chemiluminescent microparticle immunoassay., Results: Total protein intake significantly decreased with increasing strictness of vegetarian habits (median (P25; P75) in g/day: 98.6 (79.5; 123.1), 90.4 (65.9; 121.0), and 87.6 (59.8; 118.5) for OMNI, LOV and VEG, respectively; p = 0.020), and carbohydrate intake was the highest in LOV (median (P25; P75) in g/day: 231.5 (178.4; 287.9), 283.9 (227.3; 342.6), and 263.0 (222.0; 348.3) for OMNI, LOV and VEG, respectively; p = 0.001). VEG were the main users of B12 vitamin (93% in VEG vs. 17% in OMNI and 59% in LOV, p = 0.001), and LOV were the main users of iron supplements (29% in LOV vs. 14% in OMNI and 13% in VEG, p = 0.042), respectively. Blood levels of B12 vitamin correlated negatively with blood homocysteine ( r s = -0.386, p < 0.001) and positively with % muscle mass ( r s = 0.136, p = 0.005). Participants using iron supplements presented higher C-reactive protein (CRP) ( p = 0.014) and they had lower % MM ( p = 0.003). Finally, when compared to being OMNI, being LOV independently associated with: (a) having +4.8% ( p = 0.002) of fat mass, which could be due to higher carbohydrate intake, and (b) having -2.2% ( p = 0.043) of muscle mass. Our data suggest that the association between diet and muscle mass could be attenuated in VEG due to B12 supplementation and/or aggravated in LOV due to iron supplementation-associated inflammation.