HIF-PHD inhibitor desidustat ameliorates iron deficiency anemia.

Iron deficiency anemia is caused by many pathological conditions like chronic kidney disease (CKD), inflammation, malnutrition and gastrointestinal abnormality. Current treatments that are erythropoiesis stimulating agents (ESAs) and iron supplementation are inadequate and often lead to tolerance and/or toxicity. Desidustat, a prolyl hydroxylase (PHD) inhibitor, is clinically used for the treatment of anemia with CKD. In this study, we investigated the effect of desidustat on iron deficiency anemia (IDA). IDA was induced in C57BL6/J mice by iron deficient diet feeding. These mice were then treated with desidustat (15 mg/kg, PO) and FeSO4 (20 mg/kg) for five weeks and effect of the treatment on hematology, iron homeostasis, and bone marrow histology was observed. Effect of desidustat on iron metabolism in inflammation (LPS)-induced iron deficiency was also assessed. Both, Desidustat and FeSO4, increased MCV (mean corpuscular volume), MCH (mean corpuscular hemoglobin), hemoglobin, and HCT (hematocrit) in blood and increased iron in serum, liver, and spleen. Desidustat increased MCHC (mean corpuscular hemoglobin concentration) while FeSO4 treatment did not alter it. FeSO4 treatment significantly increased iron deposition in liver, and spleen, while desidustat increased iron in circulation and demonstrated efficient iron utilization. Desidustat increased iron absorption, serum iron and decreased hepcidin without altering tissue iron, while FeSO4 increased serum and tissue iron by increasing hepcidin in LPS-induced iron deficiency. Desidustat increased erythroid population, especially iron-dependent polychromatic normoblasts and orthochromatic normoblasts, while FeSO4 did not improve cell architecture. PHD inhibition by desidustat improved iron utilization in iron deficiency anemia, by efficient erythropoiesis.

Iron Deficiency and Vitamin D Deficiency Are Associated with Sleep in Females of Reproductive Age: An Analysis of NHANES 2005-2018 Data.

BACKGROUND: Iron and vitamin D deficiencies have been implicated in sleep disturbance. Although females are more susceptible to these deficiencies and frequently report sleep-related issues, few studies have examined these associations in females. OBJECTIVE: This study investigates the association of iron and vitamin D deficiencies on sleep in a nationally representative sample of females of reproductive age. METHODS: We used 2 samples of 20-49-y-old non-pregnant females from National Health and Nutrition Examination Survey (NHANES) 2005-2008 (N = 2497) and NHANES 2005-2010 and 2015-2018 (N = 6731) to examine the associations of iron deficiency (ID), iron deficiency anemia (IDA), vitamin D deficiency (VDD), vitamin D inadequacy (VDI), and the joint association of both deficiencies with sleep duration, latency, and quality. Sleep outcomes were measured using a self-reported questionnaire. We used the body iron model based on serum ferritin and serum soluble transferrin receptor to identify ID, along with hemoglobin to identify IDA cases. In addition, 25-hydroxyvitamin D levels were used to determine VDD and VDI cases. Logistic regression was used to evaluate these associations, adjusting for potential confounders. In addition, we assessed the multiplicative and additive interactions of both deficiencies. RESULTS: ID and IDA were associated with poor sleep quality, with 1.42 [95% confidence interval (CI): 1.02, 2.00)] and 2.08 (95% CI: 1.29, 3.38) higher odds, respectively, whereas VDD and VDI were significantly associated with short sleep duration, with 1.26 (95% CI: 1.02, 1.54) and 1.22 (95% CI: 1.04, 1.44) higher odds, respectively. Subjects with both nutritional deficiencies had significantly higher odds of poorer sleep quality compared with subjects with neither condition. For sleep quality, a significant multiplicative interaction was observed between ID and VDD (P value = 0.0005). No associations were observed between study exposures and sleep latency. CONCLUSIONS: Among females of reproductive age, iron and vitamin D deficiencies are associated with sleep health outcomes. The potential synergistic effect of both deficiencies warrants further assessment.

Weak response of bovine hepcidin induction to iron through decreased expression of Smad4.

Hepcidin negatively regulates systemic iron levels by inhibiting iron entry into the circulation. Hepcidin production is increased in response to an increase in systemic iron via the activation of the bone morphogenetic protein (BMP) pathway. Regulation of hepcidin expression by iron status has been proposed on the basis of evidence mainly from rodents and humans. We evaluated the effect of iron administration on plasma hepcidin concentrations in calves and the expression of bovine hepcidin by the BMP pathway in a cell culture study. Hematocrit as well as levels of blood hemoglobin and plasma iron were lower than the reference level in calves aged 1-4 weeks. Although intramuscular administration of iron increased iron-related parameters, plasma hepcidin concentrations were unaffected. Treatment with BMP6 increased hepcidin expression in human liver-derived cells but not in bovine liver-derived cells. A luciferase-based reporter assay revealed that Smad4 was required for hepcidin reporter transcription induced by Smad1. The reporter activity of hepcidin was lower in the cells transfected with bovine Smad4 than in those transfected with murine Smad4. The lower expression levels of bovine Smad4 were responsible for the lower activity of the hepcidin reporter, which might be due to the instability of bovine Smad4 mRNA. In fact, the endogenous Smad4 protein levels were lower in bovine cells than in human and murine cells. Smad4 also confers TGF-ß/activin-mediated signaling. Induction of TGF-ß-responsive genes was also lower after treatment with TGF-ß1 in bovine hepatocytes than in human hepatoma cells. We revealed the unique regulation of bovine hepcidin expression and the characteristic TGF-ß family signaling mediated by bovine Smad4. The present study suggests that knowledge of the regulatory expression of hepcidin as well as TGF-ß family signaling obtained in murine and human cells is not always applicable to bovine cells.

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

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

Helicobacter pylori-Associated Extranodal Marginal Zone Lymphoma of Mucosa-Associated Tissue in Children: A Multicenter Case Series.

OBJECTIVE: Data regarding Helicobacter pylori (H. pylori)-associated mucosa-associated lymphoid tissue (MALT) lymphoma in children are lacking. We aimed to characterize the diagnosis, management, and outcome of H. pylori-associated MALT lymphoma in pediatric patients. STUDY DESIGN: A retrospective multicenter case series of the pediatric patients with H. pylori-associated MALT lymphoma who were diagnosed during 2010-2022. RESULTS: Five children, of them three females, were identified. The mean age at diagnosis was 14.6 ± 2.4 years. The clinical presentation included abdominal pain (5/5), nausea (3/5), weight loss, night sweats, recurrent fever (1/5), and iron deficiency anemia (2/5). Endoscopic findings in both the stomach antrum and body included a fragile and hyperemic mucosa, large ulcers, extensive nodularity, and exudate. All the biopsies from the gastric mucosa were consistent with MALT lymphoma, and positive for H. pylori (by Giemsa stain). All the patients received triple therapy (amoxicillin, nitroimidazole, or a macrolide, and a proton pump inhibitor, for 14 days), and achieved H. pylori eradication. All had complete resolution of histological findings at the last follow-up. In one patient, the histology of MALT lymphoma persisted 12 months after H. pylori eradication, and only the 18-month-biopsy was free of residual disease. CONCLUSIONS: In this series of pediatric MALT lymphoma, complete resolution of disease occurred in all the patients, yet histological remission was delayed in one. This supports the importance of endoscopic follow-up.

Standardizing the evaluation and management of iron deficiency anemia secondary to heavy menstrual bleeding in the emergency department.

BACKGROUND: Comprehensive guidelines for the management of iron deficiency anemia (IDA) in adolescents with heavy menstrual bleeding (HMB) presenting to the emergency department (ED) are lacking, leading to variability in care. We aimed to standardize the evaluation and management of these patients through the development and implementation of an evidence-based algorithm using quality improvement methodology. METHODS: Baseline data of the target population identified variability across four key measures of clinical management: therapy choice and administration, laboratory evaluation, hematology service consultation, and patient disposition. Literature review and consensus from pediatric hematology and gynecology providers informed a draft algorithm that was refined in an iterative multidisciplinary process. From December 2022 to July 2023, we aimed to achieve a 25% relative increase in patients to receive optimal management per the algorithm, while using sequential Plan-Do-Study-Act (PDSA) cycles. Process measures focusing on provider documentation and balancing measures, such as ED length of stay, were assessed concurrently. RESULTS: Forty-nine patients were evaluated during four PDSA cycles. Improvement of ≥40% above baseline regarding recommended therapy administration was achieved across four PDSA cycles. Adherence to recommended therapy choice improved from 57% (baseline) to 100%, minimal laboratory evaluation from 14% to 83%, hematology consultation from 36% to 100%, and appropriate disposition from 71% to 100%. ED length of stay remained stable. CONCLUSION: Implementation of a standardized algorithm for management of IDA secondary to HMB in adolescents in the ED increased adherence to evidence-based patient care.

Proton Pump Inhibitor Use and Iron Deficiency Anemia in Celiac Patients.

INTRODUCTION: We sought to evaluate the effect of proton pump inhibitor (PPI) use on the development and severity of iron deficiency anemia (IDA) in celiac disease (CD). METHODS: We conducted a retrospective chart review of patients older than 18 years of age at Milton S. Hershey Medical Center who were diagnosed with CD. We analyzed four cohorts of celiac patients: (1) IDA diagnosis with PPI usage, (2) no IDA diagnosis with PPI usage, (3) IDA diagnosis with no PPI usage, and (4) no IDA diagnosis with no PPI usage. We also stratified celiac patients with IDA by anemia severity. RESULTS: Of 366 celiac patients, 92 (25.1%) were diagnosed with IDA, of which 60 (65.2%) were on a PPI. The mean Hgb of celiac patients with IDA on a PPI was 11.1 g/dL and 12.1 g/dL for those without PPI (p = 0.04). For all celiac patients on a PPI without IDA, the mean was 13.3 g/dL and 13.7 g/dL for those without PPI (p = 0.02). PPI use occurred in 12 (70.6%) of the 17 patients with low severity anemia, 11 (64.7%) of the 17 patients with medium severity and 6 (85.7%) of the 7 patients with severe (p = 0.55). CONCLUSIONS: There is significant association between PPI use and IDA in celiac patients (p < 0.0001). Of those with IDA on PPIs, the distribution of the severity of anemia is not statistically different compared to those not on PPI. Discontinuation of PPIs or usage of alternative acid suppressive treatments may be indicated in patients with CD and iron deficiency anemia.

Assessment of fetal cardiac functions in pregnant women with anemia: prospective, case-control study.

OBJECTIVE: To compare the fetal cardiac functions between pregnant women with iron deficiency anemia (IDA) and healthy controls. METHODS: This single-center, prospective, case-control study was conducted at a tertiary hospital. A total of 150 patients, including 50 patients with IDA and 100 healthy pregnant women at 30-34 weeks of gestation, were included in the study. Of the patients with anemia, 20 had mild anemia, 18 had moderate anemia, and 12 had severe anemia. Pulsed-wave Doppler, M-mode, and tissue Doppler imaging (TDI) were performed to evaluate fetal cardiac functions. The fetal cardiac score was calculated using the systolic, diastolic, and global hemodynamic function parameters. RESULTS: The myocardial performance index and isovolumetric relaxation time were significantly higher in the IDA group than the control group, while isovolumetric contraction time was similar. Among the tricuspid and mitral valve diastolic parameters, the E, A, and E/A values were significantly lower in the IDA group (p<0.001). Mitral and tricuspid annular plane systolic excursions (MAPSE and TAPSE, respectively) were significantly lower in the IDA group (p<0.001). The IDA group also had significantly lower values for the TDI parameters, mitral and tricuspid E', A', S', E'/A' and a significantly higher E/E' ratio (p<0.001). Upon examination of anemia subgroups, a significant decrease was observed in the tricuspid and mitral A, E, and E/A in those with severe anemia (p<0.001). M-mode Doppler analysis revealed significantly lower TAPSE and MAPSE in the patient group with severe anemia. According to the subgroup comparison of TDI findings, the patients with severe anemia had significantly lower tricuspid and mitral E', A', S' and E'/A' (p<0.001) values and a significantly higher E/E' ratio (p<0.001). The fetal cardiac score was significantly higher in the maternal IDA group compared to the control group. A significant negative correlation was found between maternal hemoglobin level and fetal cardiac score (p<0.001). CONCLUSIONS: There may be changes in the systolic and diastolic cardiac functions of the fetuses of pregnant women with IDA. This study showed an increased E/E' ratio in the fetuses of pregnant women with IDA, suggesting a decrease in fetal heart maturation. Within the IDA group, fetal cardiac functions were more affected in those with severe anemia. This article is protected by copyright. All rights reserved.

Identification and prediction of association patterns between nutrient intake and anemia using machine learning techniques: results from a cross-sectional study with university female students from Palestine.

PURPOSE: This study utilized data mining and machine learning (ML) techniques to identify new patterns and classifications of the associations between nutrient intake and anemia among university students. METHODS: We employed K-means clustering analysis algorithm and Decision Tree (DT) technique to identify the association between anemia and vitamin and mineral intakes. We normalized and balanced the data based on anemia weighted clusters for improving ML models' accuracy. In addition, t-tests and Analysis of Variance (ANOVA) were performed to identify significant differences between the clusters. We evaluated the models on a balanced dataset of 755 female participants from the Hebron district in Palestine. RESULTS: Our study found that 34.8% of the participants were anemic. The intake of various micronutrients (i.e., folate, Vit A, B5, B6, B12, C, E, Ca, Fe, and Mg) was below RDA/AI values, which indicated an overall unbalanced malnutrition in the present cohort. Anemia was significantly associated with intakes of energy, protein, fat, Vit B1, B5, B6, C, Mg, Cu and Zn. On the other hand, intakes of protein, Vit B2, B5, B6, C, E, choline, folate, phosphorus, Mn and Zn were significantly lower in anemic than in non-anemic subjects. DT classification models for vitamins and minerals (accuracy rate: 82.1%) identified an inverse association between intakes of Vit B2, B3, B5, B6, B12, E, folate, Zn, Mg, Fe and Mn and prevalence of anemia. CONCLUSIONS: Besides the nutrients commonly known to be linked to anemia-like folate, Vit B6, C, B12, or Fe-the cluster analyses in the present cohort of young female university students have also found choline, Vit E, B2, Zn, Mg, Mn, and phosphorus as additional nutrients that might relate to the development of anemia. Further research is needed to elucidate if the intake of these nutrients might influence the risk of anemia.

Production of iron-enriched yeast and it's application in the treatment of iron-deficiency anemia.

Iron deficiency anemia (IDA) is one of the most serious forms of malnutrition. Wild type strains of Saccharomyces cerevisiae have higher tolerance to inorganic iron and higher iron conversion and accumulation capacity. The aim of this study was to investigate the effect of S. cerevisiae enriched iron as a potential organic iron supplement on mice with iron deficiency anemia. 60 male Kunming mice (KM mice, with strong adaptability and high reproduction rate, it can be widely used in pharmacology, toxicology, microbiology and other research) were randomly divided into normal control group and iron deficiency diet model group to establish IDA model. After the model was established, IDA mice were randomly divided into 5 groups: normal control group, IDA group, organic iron group (ferrous glycinate), inorganic iron group (ferrous sulfate) and S. cerevisiae enriched iron group. Mice in the experimental group were given different kinds of iron by intragastric administration once a day for 4w. The results showed that S. cerevisiae enriched iron had an effective recovery function, and the body weight and hematological parameters of IDA mice returned to normal levels. The activities of superoxide dismutase, glutathione peroxidase and total antioxidant capacity in serum were increased. In addition, the strain no. F8, able to grow in an iron-rich environment, was more effective in alleviating IDA and improving organ indices with fewer side effects compared to ferrous glycinate and ferrous sulfate groups. This study suggests that the iron-rich strain no. F8 may play an important role in improving IDA mice and may be developed as a new iron supplement.

Hypophosphatemia attenuates improvements in vitality after intravenous iron treatment in patients with inflammatory bowel disease.

PURPOSE: Iron deficiency anemia is common in people with inflammatory bowel disease (IBD), causing deterioration in quality of life, which can be reversed by treatment that increases iron stores and hemoglobin levels. The present post hoc analyses estimate health state utility values for patients with IBD after treatment with ferric derisomaltose or ferric carboxymaltose and evaluate the health domains driving the changes. METHODS: SF-36v2 responses were recorded at baseline and day 14, 35, 49, and 70 from 97 patients enrolled in the randomized, double-blind, PHOSPHARE-IBD trial (ClinicalTrials.gov ID: NCT03466983), in which patients with IBD across five European countries were randomly allocated to either ferric derisomaltose or ferric carboxymaltose. Changes in SF-36v2 scale scores and SF-6Dv2 health utility values were analyzed by mixed models. RESULTS: In both treatment arms, SF-6Dv2 utility values and all SF-36v2 scale scores, except Bodily Pain, improved significantly (p = < 0.0001). The improvement in SF-6Dv2 utility values showed no significant treatment group difference. The improvement in utility values was completely explained by improvement in Vitality scores. Vitality scores showed significantly larger improvement with ferric derisomaltose versus ferric carboxymaltose (p = 0.026). Patients with the smallest decrease in phosphate had significantly larger improvements in Vitality scores at each time point (p = < 0.05 for all comparisons) and overall (p = 0.0006). CONCLUSIONS: Utility values improved significantly with intravenous iron treatment. Improvement in utility values was primarily driven by Vitality scores, which showed significantly greater improvement in the ferric derisomaltose arm. Smaller decreases in phosphate were associated with significantly higher Vitality scores, suggesting that quality of life improvement is attenuated by hypophosphatemia. The utility values can inform future cost-utility analysis.

Impact of litter size on the hematological and iron status of gilts, sows and newborn piglets: a comparative study of domestic pigs and wild boars.

BACKGROUND: The critically low hepatic iron stores of newborn piglets are considered to be a major cause of neonatal iron deficiency in modern breeds of domestic pig (Sus domestica). The main factor believed to contribute to this phenomenon is large litter size, which has been an objective of selective breeding of pigs for decades. As consequence, iron transferred from the pregnant sow has to be distributed among a greater number of fetuses. RESULTS: Here, we investigated whether litter size influences red blood cell (RBC) indices and iron parameters in Polish Large White (PLW) piglets and gilts. Small and large litters were produced by the transfer of different numbers of embryos, derived from the same superovulated donor females, to recipient gilts. Piglets from large litters obtained following routine artificial insemination were also examined. Our results clearly demonstrated that varying the number of piglets in a litter did not affect the RBC and iron status of 1-day-old piglets, with all showing iron deficiency anemia. In contrast, gilts with small litters displayed higher RBC and iron parameters compared to mothers with large litters. A comparative analysis of the RBC status of wild boars (having less than half as many piglets per litter as domestic pigs) and PLW pigs, demonstrated higher RBC count, hemoglobin level and hematocrit value of both wild boar sows and piglets, even compared to small-litter PLW animals. CONCLUSIONS: These findings provide evidence that RBC and iron status in newborn PLW piglets are not primarily determined by litter size, and indicate the need to study the efficiency of iron transport across the placenta in domestic pig and wild boar females.

Iron deficiency anemia status in Iranian pregnant women and children: an umbrella systematic review and meta-analysis.

BACKGROUND: Iron deficiency anemia (IDA) is a global health challenge, especially affecting females and children. We aimed to conduct an umbrella systematic review of available evidence on IDA's prevalence in Iranian pregnant women and children. METHODS: We searched the Web of Science, Science Direct, PubMed, Scopus, and Google Scholar databases for articles published by April 2023. Meta-analyses investigating the status of IDA in Iran were included. The findings of seven meta-analyses comprising 189,627 pregnant women with a mean age of 26 and 5,890 children under six years old were included in this study. The methodological quality of each study was evaluated with the Assessment of Multiple Systematic Reviews (AMSTAR2) instrument. RESULTS: We estimated the prevalence of IDA at 15.71% in pregnant women and 19.91% in young children. According to our subgroup analysis of pregnant women, IDA's prevalence in urban and rural regions was 16.32% and 12.75%; in the eastern, western, central, southern, and northern regions of Iran, it was estimated at 17.8%, 7.97%, 19.97%, 13.45%, and 17.82%, respectively. CONCLUSION: IDA is common in young children and pregnant females and is a significant public health concern in Iran. The present umbrella review results estimated that Iran is in the mild level of IDA prevalence based on WHO classification. However, due to sanctions and high inflation in Iran, the prevalence of anemia is expected to increase in recent years. Multi-sectoral efforts are required to improve the iron status of these populations and reduce the burden of IDA in the country.

Effect of ferric citrate hydrate on fibroblast growth factor 23 and platelets in non-dialysis-dependent chronic kidney disease and non-chronic kidney disease patients with iron deficiency anemia.

BACKGROUND: Iron deficiency anemia (IDA) increases levels of C-terminal fibroblast growth factor 23 (cFGF23) and platelet count (PLT), each of which is associated with cardiovascular events. Therefore, we hypothesized that iron replacement with ferric citrate hydrate (FC) would decrease cFGF23 levels and PLT in patients with IDA. METHODS: In a randomized, open-label, multicenter, 24-week clinical trial, patients with non-dialysis-dependent chronic kidney disease (CKD) and non-CKD complicated by IDA (8.0 ≤ hemoglobin < 11.0 g/dL; and serum ferritin < 50 ng/mL [CKD]; < 12 ng/mL [non-CKD]) were randomized 1:1 to FC-low (500 mg: approximately 120 mg elemental iron/day) or FC-high (1000 mg: approximately 240 mg elemental iron/day). If sufficient iron replacement had been achieved after week 8, further treatment was discontinued. RESULTS: Seventy-three patients were allocated to FC-low (CKD n = 21, non-CKD n = 15) and FC-high (CKD n = 21, non-CKD n = 16). Regardless of CKD status, FC increased serum ferritin and transferrin saturation, did not change intact FGF23 or serum phosphorus, but decreased cFGF23. In FC-low group, median changes in cFGF23 from baseline to week 8 were -58.00 RU/mL in CKD and -725.00 RU/mL in non-CKD; in FC-high group, the median changes were -66.00 RU/mL in CKD and -649.50 RU/mL in non-CKD. By week 8, FC treatment normalized PLT in all patients with high PLT at baseline (>35.2 × 104/µL; FC-low: 1 CKD, 8 non-CKD; FC-high: 3 CKD, 8 non-CKD). CONCLUSION: Regardless of CKD status, iron replacement with FC decreased elevated cFGF23 levels and normalized elevated PLT in patients with IDA. CLINICAL TRIAL REGISTRATION NUMBER: jRCT2080223943.

Iron Status, Thyroid Dysfunction, and Iron Deficiency Anemia: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: Given the clinical association between thyroid dysfunction and iron deficiency anemia (IDA), as well as their shared association with iron status, this study aimed to investigate the causal relationship between iron status and thyroid dysfunction, while also examining the risk of IDA in relation to thyroid dysfunction. METHODS: A two-sample mendelian randomization (MR) study was conducted to identify the causal relationship of iron status on thyroid dysfunction, as well as thyroid dysfunction on IDA. Large-scale European population-based genome-wide association study databases were utilized (Genetics of Iron Status consortium, ThyroidOmics consortium, FinnGen consortium, and UK Biobank). Inverse variance-weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results. RESULTS: The IVW estimates did not reveal any significant causal relationship between serum iron status markers and thyroid dysfunction. However, a significant causal relationship was observed between hypothyroidism and IDA (odds ratio [OR] = 1.101, 95% confidence interval [CI] = 1.048-1.157, p < 0.001). Repeated analyses also demonstrated a similar trend (OR = 1.023, 95% CI = 1.011-1.035, p < 0.001). Sensitivity analysis supported that the MR estimates were robust. CONCLUSION: In our MR study, an upregulation of the hypothyroidism-associated gene was found to be significantly associated with an elevated risk of IDA in the European population. These findings may offer novel therapeutic insights for clinicians managing patients with hypothyroidism, IDA, or their comorbidities.

Unlocking Optimal Glycemic Interpretation: Redefining HbA1c Analysis in Female Patients With Diabetes and Iron-Deficiency Anemia Using Machine Learning Algorithms.

OBJECTIVE: In response to the nuanced glycemic challenges faced by women with iron deficiency anemia (IDA) associated with diabetes, this study uses advanced machine learning algorithms to redefine hemoglobin (Hb)A1c measurement values. We aimed to improve the accuracy of glycemic interpretation by recognizing the critical interaction between erythrocytes, iron, and glycemic levels in this specific demographic group. METHODS: This retrospective observational study included 17,526 adult women with HbA1c levels recorded from 2017 to 2022. Samples were classified as diabetic, prediabetic, or non-diabetic based on HbA1c and fasting blood glucose (FBG) levels for distribution analysis without impacting model training. Support Vector Machines, Linear Regression, Random Forest, and K-Nearest Neighbor algorithms as machine learning (ML) methods were used to predict HbA1c levels. Following the training of the model, HbA1c values were predicted for the IDA samples using the trained model. RESULTS: According to our results, there has been a 0.1 unit change in HbA1c values, which has resulted in a clinical decision change in some patients. DISCUSSION: Using ML to analyze HbA1c results in women with IDA may unveil distinctions among patients whose HbA1c values hover near critical medical decision thresholds. This intersection of technology and laboratory science holds promise for enhancing precision in medical decision-making processes.

Dietary intakes of iron, folate, and vitamin B12 during pregnancy and correlation with maternal hemoglobin and fetal growth: findings from the ROLO longitudinal birth cohort study.

PURPOSE: Dietary micronutrient intakes of iron, folate and vitamin B12 are known to influence hemoglobin. Low maternal hemoglobin (maternal anemia) has been linked to low birthweight and other adverse health outcomes in the fetus and infant. Our primary aim was to explore relationships between maternal dietary micronutrient intakes, maternal full blood count (FBC) parameters and fetal abdominal circumference (AC) and estimated fetal weight (EFW) growth trajectories. Secondarily, we aimed to assess relationships between maternal dietary micronutrient intakes, maternal hemoglobin values and placental weight and birthweight. METHODS: Mother-child pairs (n = 759) recruited for the ROLO study were included in this analysis. Maternal dietary micronutrient intakes were calculated from food diaries completed during each trimester of pregnancy. FBC samples were collected at 13- and 28-weeks' gestation. Fetal ultrasound measurements were recorded at 20- and 34-weeks' gestation. Growth trajectories for AC and EFW were estimated using latent class trajectory mixture models. RESULTS: Dietary intakes of iron and folate were deficient for all trimesters. Mean maternal hemoglobin levels were replete at 13- and 28-weeks' gestation. Dietary iron, folate and vitamin B12 intakes showed no associations with fetal growth trajectories, placental weight or birthweight. Lower maternal hemoglobin concentrations at 28 weeks' gestation were associated with faster rates of fetal growth and larger placental weights and birthweights. CONCLUSION: The negative association between maternal hemoglobin at 28 weeks' gestation and accelerated fetal and placental growth may be due to greater consumption of maternal iron and hemoglobin by fetuses' on faster growth trajectories in addition to placental biochemical responses to lower oxygen states.

Preparation of Rehmanniae Radix Praeparata Polysaccharide Iron(III) Complex and Evaluation of Its Biological Activity.

This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its iron (III) complex, RGP-Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1→3; 1→2, 3; and 1→2, 3, 4 linkages, among others. RGP-Fe(III) had a molecular weight of 4.39×104 Da. Notably, RGP-Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP-Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP-Fe(III) on the liver and spleen. These findings suggest the potential of RGP-Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties.

Endoscopic findings and predictors of gastrointestinal lesions in children with iron deficiency anemia.

Iron deficiency anemia (IDA) can be caused by occult gastrointestinal (GI) blood loss; however, the endoscopic findings in children with anemia are unclear. The study aimed to determine the frequency and factors related to lesions in children with IDA undergoing endoscopy. We retrospectively analyzed the clinical and endoscopic findings of children with a laboratory-based diagnosis of IDA. Of 58 patients, 36 (62.1%) had upper GI tract lesions, with erosive gastritis being the most common lesion. Further, 26 patients underwent concomitant colonoscopy, and 12 (46.2%) had lower GI tract lesions. Overall, 44 (75.9%) patients had lesions in either the upper or lower GI tract. Helicobacter pylori infection was detected in 13 patients (22.4%). Patients with lesions found by endoscopy had significantly lower hemoglobin level (8.9 vs. 10.0 g/dL, p = 0.047) and mean corpuscular volume (75.5 vs. 80.9 fL, p = 0.038). The proportion of patients with previous treatment for IDA was also higher in those with lesions on endoscopy. In multivariate analysis, age of ≥10 years (odds ratio [OR], 6.00; 95% confidence Interval [CI], 0.56-10.75) and positive fecal occult blood test (FOBT) findings (OR, 2.25; 95% CI, 0.14-4.52) were factors related to GI lesions. The presence of GI symptoms was not associated with GI lesions. A high proportion of GI lesions were found by endoscopy in children with IDA in this study. Endoscopy should be considered in children with IDA even without GI symptoms, especially in older children, and those with positive FOBT results.

Autoimmune Gastritis and Hypochlorhydria: Known Concepts from a New Perspective.

Autoimmune atrophic gastritis is an immune-mediated disease resulting in autoimmune destruction of the specialized acid-producing gastric parietal cells. As a consequence, in autoimmune atrophic gastritis, gastric acid secretion is irreversibly impaired, and the resulting hypochlorhydria leads to the main clinical manifestations and is linked, directly or indirectly, to the long-term neoplastic complications of this disease. In the last few years, autoimmune atrophic gastritis has gained growing interest leading to the acquisition of new knowledge on different aspects of this disorder. Although reliable serological biomarkers are available and gastrointestinal endoscopy techniques have substantially evolved, the diagnosis of autoimmune atrophic gastritis is still affected by a considerable delay and relies on histopathological assessment of gastric biopsies. One of the reasons for the diagnostic delay is that the clinical presentations of autoimmune atrophic gastritis giving rise to clinical suspicion are very different, ranging from hematological to neurological-psychiatric up to gastrointestinal and less commonly to gynecological-obstetric symptoms or signs. Therefore, patients with autoimmune atrophic gastritis often seek advice from physicians of other medical specialties than gastroenterologists, thus underlining the need for increased awareness of this disease in a broad medical and scientific community.