Introduction: Sites associated with gadolinium (Gd) deposition in the brain (e.g., the globus pallidus) are known to contain high concentrations of ferric iron. There is considerable debate over the mechanism of Gd deposition in the brain. The role of iron transport mechanisms in Gd deposition has not been determined. Thus, we seek to identify if Gd deposition can be controlled by modifying iron exposure. Methods: Female Sprague-Dawley rats were given diets with controlled iron levels at 2-6 ppm, 6 ppt (20 g/kg Fe carbonyl) or 48 ppm for 3 weeks to induce iron deficiency, overload or normalcy. They were kept on those diets while receiving a cumulative 10 mmol/kg dose of gadodiamide intravenously over 2 weeks, then left to washout gadodiamide for 3 days or 3 weeks before tissues were harvested. Gd concentrations in tissues were analyzed by ICP-MS. Results: There were no significant effect of dietary iron and total Gd concentrations in the organs, but there was a significant effect of iron status on Gd distribution in the brain. For the 3-week washout cohort, there was a non-significant trend of increasing total brain deposition and decreasing dietary iron, and about 4-fold more Gd in the olfactory bulbs of the low iron group compared to the other groups. Significant brain accumulation was observed in the low iron group total brain Gd in the 3-week washout group relative to the 3-day washout group and no accumulation was observed in other tissues. There was a strong negative correlation between femur Gd concentrations and concentrations in other organs when stratifying by dietary iron. Discussion: Gd brain deposition from linear Gd-based contrast agents (GBCAs) are dependent upon iron status, likely through variable transferrin saturation. This iron dependence appears to be associated with redistribution of peripheral deposited Gd (e.g., in the bone) into the brain.

Pica is an eating disorder defined as the compulsive and repeated ingestion of substances that have no nutritional value for at least one month. This condition may be hard to diagnose without complications, as a high degree of suspicion is needed. The subject in this case was a teenager who presented with asthenia and unspecific abdominal pain. The etiological workup showed no abnormalities other than mild anemia and iron and folate deficiencies. After a thorough anamnesis, the patient\'s mother mentioned sporadic ingestion of synthetic mattress foam since childhood, which had become more frequent in the previous year. With this key information, it was possible to establish a diagnosis before serious complications occurred and thus help the patient get the necessary assistance by referring them to pediatrics, nutrition, and child and adolescent psychiatry consultations. This case report highlights the importance of a detailed anamnesis, particularly when dealing with unspecific symptoms, exploring the possibility of disorders that are rarely thought of, such as pica. It also recaps how important it is to address sensitive topics like eating disorders and create an open environment with no judgment, as these attitudes are crucial to ensuring the correct diagnosis and providing the best care for patients.

Objective. To evaluate the evidence regarding the association between iron deficiency anemia (IDA) and dental caries in children and adolescents. Methods. Searches were conducted in 4 international databases from the beginning of records until October 2023. Studies evaluating the association between IDA and dental caries in individuals aged 6 months to 18 years were included. Risk of bias was assessed using the Newcastle Ottawa Scale. Quantitative synthesis was performed using the inverse variance or Mantel-Haenzel method, depending on the type of outcome analyzed. Measures of association included odds ratios and mean differences, employing a random-effects model with a 95% confidence interval. Results. A total of 1161 studies were identified, of which 12 were selected for qualitative review and 9 for meta-analysis. A significant association was found between IDA and dental caries (odds ratio of 3.54; 95% CI: 2.54-4.94) and a higher rate of dental caries in the presence of IDA (mean difference of 1.96; 95% CI: 1.07-2.85). The certainty of evidence according to GRADE was rated as very low. Conclusions. Despite the limited certainty, the findings indicate a significant association between IDA and dental caries. It is prudent to interpret these results with caution, considering the methodological limitations of the studies. However, given the potential relevance of this association for public health, recommending oral health strategies, including preventive and corrective dental interventions, for anemia control programs underlines the importance of more rigorous future research to strengthen the certainty of the evidence and guide the implementation of these strategies.

Background: Iron deficiency (ID) is common in patients with pulmonary arterial hypertension and has been associated with increased morbidity and mortality. We aimed to evaluate the therapeutic effects of iron supplementation in iron deficient patients with group 1 to 4 pulmonary hypertension (PH). Methods: A total of 85 PH patients (mean age 69.8 ± 12.0 years, 56.5% female) were included in this prospective trial. Patients were screened for ID at baseline. PH patients with ID received intravenous iron supplementation (500-1000 mg ferric carboxymaltose). PH patients without ID served as control group. At baseline and 16-week follow up, six-minute walk test (6MWT), laboratory testing and echocardiography were performed. Additionally, World Health Organization (WHO) functional class, fatigue score and quality of life (QoL) by the SF-36 questionnaire were assessed. Results: Overall, ID was present in 26.7% (n=8/30), 37.5% (n=9/24), 45.5% (n=10/22) and 44.4% (n=4/9) of patients in PH groups 1-4, respectively. In the total study population, iron restoration led to a significant mitigation of fatigue (p=0.01). However, 6MWT, WHO function class, NT-proBNP levels, QoL and right ventricular function did not change significantly. With regard to the underlying PH group, only PH group 3 patients experienced significant improvements in 6MWT distance (p=0.019), WHO functional class (p=0.017), fatigue (p=0.009) and some QoL domains, as compared to controls. Conclusions: ID was common in PH groups 1 to 4. Though intravenous iron supplementation adequately restored iron status and improved fatigue throughout all patients, in the underlying PH groups treatment was accompanied by improvements in exercise capacity, WHO function class and fatigue only in group 3 PH.

Iron is an important cofactor for many proteins and is used to create Fe-S clusters and heme prosthetic groups that enzymes use to catalyze enzymatic reactions. Proteins involved in the import, export, and sequestration of iron are regulated by Iron Regulatory Proteins (IRPs). Recently, a patient with bi-allelic loss of function mutations in IREB2 leading to the absence of IRP2 protein was discovered. The patient failed to achieve developmental milestones and was diagnosed with dystonic cerebral palsy, epilepsy, microcytic hypochromic anemia, and frontal lobe atrophy. Several more IREB2 deficient patients subsequently identified manifested similar neurological problems. To better understand the manifestations of this novel neurological disease, we subjected an Irp2-null mouse model to extensive behavioral testing. Irp2-null mice had a significant motor deficit demonstrated by reduced performance on rotarod and hanging wire tests. Somatosensory function was also compromised in hot and cold plate assays. Their spatial search strategy was impaired in the Barnes maze and they exhibited a difficulty in flexibly adapting their response in the operant touchscreen reversal learning task. The latter is a cognitive behavior known to require an intact prefrontal cortex. These results suggest that loss of Irp2 in mice causes motor and behavioral deficits that faithfully reflect the IREB2 patient\'s neurodegenerative disorder.

Although it has been established that patients with chronic kidney disease and iron deficiency, as indicated by a transferrin saturation of < 20%, are at increased risk of all-cause mortality and cardiovascular events, the optimal management of such patients has not yet been determined. In this post hoc subgroup analysis, we aimed to clarify the effect of ferric citrate hydrate on transferrin saturation in patients with chronic kidney disease and low transferrin saturation (< 20%) undergoing hemodialysis. To accomplish this, we extracted the relevant data on a subset of patients drawn from two previous studies: the ASTRIO study (A Study examining the contribution to Renal anemia treatment with ferric citrate hydrate, Iron-based Oral phosphate binder, UMIN000019176) and a post-marketing surveillance study. The subset of patients used for the present study were those with baseline transferrin saturation < 20%. We found that administration of ferric citrate hydrate increased transferrin saturation and maintained transferrin saturation at approximately 30%. However, because we did not have access to data on all-cause mortality or cardiovascular events, we could not ascertain whether the frequency of these outcomes was reduced in parallel with improvements in transferrin saturation. Further large studies are required.

UNASSIGNED: Women of reproductive age are at elevated risk of iron deficiency (ID) and anemia; in the United States, those of Hispanic/Latino background are at especially high risk. Causes of ID and anemia and variations in risk within Hispanic/Latino women of reproductive age are not well described.
UNASSIGNED: To characterize ID and anemia and their risk factors/markers in Hispanic/Latina women.
UNASSIGNED: Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were used. HCHS/SOL enrolled participants in 2008-2011 at 4 sites: Bronx, Chicago, Miami, and San Diego; 5386 were non-pregnant women ages 18-49 y. Primary outcomes were ID (ferritin <30 μg/L) and anemia (hemoglobin <12 g/dL). Predictors were background/heritage, Short Acculturation Scale for Hispanics scores, years lived in the United States, and interview language, diet summarized in the Alternate Healthy Eating Index 2010, sociodemographic covariates, and study site. Main analyses used survey log binomial regressions adjusted for age, site, and smoking.
UNASSIGNED: Almost half (42%) of participants were of Mexican background, 15% of Cuban background, and <15% each were of Puerto Rican, Dominican, Central American, or South American background. ID prevalence was 34.4% overall but differed by site-background pairings. The lowest and highest prevalence were 26% and 42% among women of Cuban background in Miami and women of Mexican background in Chicago, respectively. Anemia prevalence was 16% and ranged from 8.9% (Central American background/Miami) to 22% (Dominican background/Bronx). Acculturation, sociodemographic, and diet variables examined did not explain observed prevalence differences by site/background.
UNASSIGNED: Prevalence of ID and anemia were high among HCHS/SOL women and differed by field center and background. These differences highlight the importance of characterizing nutritional risk by background within Hispanic/Latino women.

BACKGROUND: Heavy menstrual bleeding affects up to two thirds of women on oral anticoagulation. The rates of heavy menstrual bleeding, its impact on quality of life and associated risk factors in women attending anticoagulation clinics in South Africa are largely unknown.
METHODS: A prospective cohort study was performed over an eight-month period in women on Warfarin (n = 30) and Rivaroxaban (n = 27) for a median [interquartile range] duration of 15.5 [78.0] months attending an anticoagulation clinic in Johannesburg, South Africa. Heavy menstrual bleeding was assessed over one menstrual cycle using the validated pictorial blood loss assessment charts (PBAC) and the menstrual bleeding questionnaire (MBQ).
RESULTS: In this population of predominantly African ethnicity, with a median age of 39 [8] years, 39 (68.4%) women experienced heavy menstrual bleeding, defined as a PBAC score of >100. Median cycle length on anticoagulation and MBQ scores were significantly higher among women with a PBAC score of >100 (p > 0.05). Univariate analysis identified Rivaroxaban as a risk factor for heavy menstrual bleeding (OR 5.03, 95% CI 1.40-18.12). Heavy menstrual bleeding required treatment in 29 (74.4%) women which included management of iron deficiency, anti-fibrinolytics, modification of anticoagulation and hormonal contraception.
CONCLUSIONS: Heavy menstrual bleeding was associated with a considerable negative impact on quality of life. This was most significant for women on Rivaroxaban as compared to Warfarin. It is essential to monitor and appropriately treat heavy menstrual bleeding in at risk women on anticoagulant treatment.

Background. Iron deficiency (ID) is a significant, high-prevalence comorbidity in chronic heart failure (HF) that represents an independent predictor of a worse prognosis. However, a clear-cut diagnosis of ID in HF patients is not assured. The soluble transferrin receptor (sTfR) is a marker that reflects tissue-level iron demand and may be an early marker of ID. However, the impact of sTfR levels on clinical outcomes in non-anemic HF patients with a normal systemic iron status has never been evaluated. Methods. This is a post hoc analysis of an observational, prospective cohort study of 1236 patients with chronic HF of which only those with normal hemoglobin levels and a normal systemic iron status were studied. The final cohort consisted of 215 patients. Tissue ID was defined as levels of sTfR > 75th percentile (1.65 mg/L). Our aim was to describe the association between sTfR and clinical outcomes (all-cause death and HF hospitalization) and to explore its association with a wide array of serum biomarkers. Results. The sTfR level (HR 1.48, 95% CI 1.13-1.96, p = 0.005) and tissue ID (HR 2.14, 95% CI 1.22-3.75, p = 0.008) was associated with all-cause death. However, we found no association between sTfR levels and the risk of HF hospitalization. Furthermore, high sTfR levels were associated with a worse biomarker profile indicating myocardial damage (troponin and NT-proBNP), systemic inflammation (CRP and albumin), and impaired erythropoiesis (erythropoietin). Conclusions. In this cohort, the presence of tissue ID defined by sTfR levels is an independent factor for all-cause death in patients with normal systemic iron parameters.

BACKGROUND: Intravenous iron supplementation has been reported to provide a superior safety profile and effectiveness in the treatment of iron deficiency anemia (IDA) compared to traditional oral iron supplements.
OBJECTIVE: To assess preference for intravenous iron versus oral iron among patients with IDA at King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
METHODS: This observational cross-sectional study included 267 adults diagnosed with IDA or on treatment for IDA at King Abdulaziz University Hospital between February 2023 and March 2024. A specially modified questionnaire was used for the collection of data, which included demographic and treatment-related data. The values of the variables are presented as mean and standard deviation or median and interquartile range. Differences with an asymptotic two-tailed P-value of less than 0.05 were considered to be statistically significant.
RESULTS: The majority of the included patients were women (95.5%), Saudi nationals (90.6%), and from the Western region (98.1%). About half of the included patients were receiving intravenous iron supplementation (51.7%), and the other half were receiving oral iron supplements (48.3%). However, the majority of the patients (74.9%) reported that they preferred intravenous iron treatment. With regard to factors that affected their preference, education level (P = 0.044), employment status (P = 0.009), and income level (P = 0.007) were identified as significant predictors. Among the patients who preferred oral iron therapy, the reason cited by the majority, that is, 79.1%, was that tablets were easier to adhere to than needles, while 50.7% stated that tablets had fewer side effects than needles and 64.2% reported a fear of needles. Among the patients who preferred intravenous iron therapy, the majority, that is, 82.4%, stated that intravenous administration was easier for them. Further, 73.5% were of the opinion that intravenous iron therapy had fewer side effects (73.5%), 27.7% reported that they were unable to swallow iron tablets, and 52.5% reported that they had difficulty remembering to take iron tablets. About a third of patients discontinued oral iron therapy due to changes in bowel habits (35%). Although 18.7% of the patients reported feeling pain with intravenous iron therapy, the majority were satisfied (79.4%) and recommended intravenous iron treatment for anemia to friends and family members (84.6%). In contrast, more than half of the patients on oral therapy were uncomfortable (56.2%) with the treatment. Further, 37.1% were not satisfied with their iron tablets, and 25.1% of patients stated that they would not recommend iron tablets for anemia treatment to their friends or family members.
CONCLUSIONS: The majority of the patients preferred intravenous iron therapy to correct IDA because oral therapy was associated with difficulties related to swallowing iron tablets and remembering to take the tablets. Although the results indicate that both therapies have similar effectiveness, patients receiving intravenous treatment appeared to be more satisfied with the treatment and recommended it to friends and family.