Consumption of Iron-Fortified Lentils Is Protective against Declining Iron Status among Adolescent Girls in Bangladesh: Evidence from a Community-Based Double-Blind, Cluster-Randomized Controlled Trial.

BACKGROUND: In many low-income countries, iron deficiency (ID) and its anemia (IDA) pose significant health challenges, particularly among females and girls. Finding sustainable and effective solutions to address this issue is critical. OBJECTIVES: This study aimed to evaluate the efficacy of incorporating iron-fortified lentils (IFLs) into the diets of rural Bangladeshi adolescent girls on their body iron (Fe) status. METHODS: A community-based, double-blind, cluster-randomized controlled trial involved n = 1195 girls aged 10-17 y. A total of 48 adolescent clubs (n = ∼27 girls each) were randomized into 3 groups: 1) 200 g cooked IFLs, 2) 200 g cooked noniron-fortified lentils (NIFLs), and 3) a control group with no lentils (usual dietary intake). The intervention, administered 5 days a week for 85 feeding days, provided ∼8.625 mg Fe from each serving of IFLs and 2.625 mg from NIFLs. Blood samples collected at baseline, midpoint (42 feeding days), and endpoint (85 feeding days) assessed key Fe and inflammation biomarkers. Statistical analyses were filtered for inflammation. RESULTS: Although all groups experienced a decline in Fe status over time, the IFL group exhibited a significantly reduced decline in serum ferritin (sFer -7.2 µg/L), and total body iron (TBI -0.48 mg/kg) level compared with NIFL (sFer -14.3 µg/L and TBI -1.36 mg/kg) and usual intake group (sFer -12.8 µg/L and TBI -1.33 mg/kg). Additionally, those in the IFL group had a 57% reduced risk of developing clinical ID (sFer <15 µg/L) compared with the usual intake group. CONCLUSIONS: Our findings suggest that incorporating IFLs into the diet can help mitigate a decline in sFer, indicating a positive impact on the body Fe status of adolescent girls. This research underscores the potential role of fortified foods in addressing ID and IDA in vulnerable populations, emphasizing the significance of food-based interventions in public health. TRIAL REGISTRATION NUMBER: This trial was registered at the clinicaltrials.gov on May 24, 2018 (https://clinicaltrials.gov/study/NCT03516734?locStr=Bangladesh&country=Bangladesh&distance=50&cond=Anemia&intr=Iron%20fortified%20lentils&rank=1) as NCT03516734.

Urinary Ferritin as a Noninvasive Means of Assessing Iron Status in Young Children.

BACKGROUND: Iron deficiency (ID) is the most common nutritional deficiency affecting young children. Serum ferritin concentration is the preferred biomarker for measuring iron status because it reflects iron stores; however, blood collection can be distressing for young children and can be logistically difficult. A noninvasive means to measure iron status would be attractive to either diagnose or screen for ID in young children. OBJECTIVES: This study aimed to determine the correlation between urinary and serum ferritin concentrations in young children; to determine whether correcting urinary ferritin for creatinine and specific gravity improves the correlation; and to determine a urine ferritin cut point to predict ID. METHODS: Validation study was conducted using paired serum and urine collected from 3-y-old children (n = 142) participating in a longitudinal birth cohort study: the ORIGINS project in Perth, Western Australia. We calculated the sensitivity, specificity, positive, and negative predictive values of urinary ferritin amount in identifying those with ID at the clinical cut point used by the World Health Organization (serum ferritin concentration of <12 ng/mL). RESULTS: Urine ferritin, corrected for creatinine, correlated moderately with serum ferritin [r = 0.53 (0.40-0.64)] and performed well in predicting those with ID (area under the curve: 0.85; 95% confidence interval: 0.75, 0.94). Urine ferritin <2.28 ng/mg creatinine was sensitive (86%) and specific (77%) in predicting ID and had a high negative predictive value of 97%; however, the positive predictive value was low (40%) owing to the low prevalence of ID in the sample (16%). CONCLUSIONS: Urine ferritin shows good diagnostic performance for ID. This noninvasive biomarker maybe a useful screening tool to exclude ID in healthy young children; however, further research is needed in other populations.

Revisiting iron overload status and change thresholds as predictors of mortality in transfusion-dependent ß-thalassemia: a 10-year cohort study.

Data on iron overload status and change thresholds that can predict mortality in patients with transfusion-dependent ß-thalassemia (TDT) are limited. This was a retrospective cohort study of 912 TDT patients followed for up to 10 years at treatment centers in Italy (median age 32 years, 51.6% female). The crude mortality rate was 2.9%. Following best-predictive threshold identification through receiver operating characteristic curve analyses, data from multivariate Cox-regression models showed that patients with Period Average Serum Ferritin (SF) > 2145 vs ≤ 2145 ng/mL were 7.1-fold (P < 0.001) or with Absolute Change SF > 1330 vs ≤ 1330 ng/mL increase were 21.5-fold (P < 0.001) more likely to die from any cause. Patients with Period Average Liver Iron Concentration (LIC) > 8 vs ≤ 8 mg/g were 20.2-fold (P < 0.001) or with Absolute Change LIC > 1.4 vs ≤ 1.4 mg/g increase were 27.6-fold (P < 0.001) more likely to die from any cause. Patients with Index (first) cardiac T2* (cT2*) < 27 vs ≥ 27 ms were 8.6-fold (P < 0.001) more likely to die from any cause. Similarly, results at varying thresholds were identified for death from cardiovascular disease. These findings should support decisions on iron chelation therapy by establishing treatment targets, including safe iron levels and clinically meaningful changes over time.

A convenient and practical index for predicting the induction response in adult patients with hemophagocytic lymphohistiocytosis: ferritin/platelet ratio.

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome with high mortality rate. The response to induction therapy is an important factor affecting survival. The purpose is to investigate laboratory predictors for induction response in adult patients with HLH, which are convenient, practical, and timeliness. Clinical data from January 2017 to December 2020 was retrospectively analyzed, and 269 patients were included. Patients were divided into remission and non-remission groups according to their induction response, 177 in the remission group, and 92 in the non-remission group. We reviewed general characteristics and analyzed the predictive value of serum ferritin, triglycerides, alanine aminotransferase (ALT), and blood cells before and 1-4 weeks after induction therapy for induction response by univariate analysis, ROC curves, etc. There was a correlation between serum ferritin, ALT, leukocytes, neutrophils, hemoglobin, platelets, and induction response (P < 0.05). Serum ferritin and platelets 1-4 weeks after induction therapy, respectively, might be a good predictor for induction response in adults with HLH, with AUC values close to or greater than 0.7. We established a new clinical model of the ferritin/platelet ratio. The results showed that the ferritin/platelet ratio at 1-4 weeks after induction therapy might be a practical index for predicting induction response, which significantly improved the area under the ROC curve (AUC > 0.75). Patients with a ferritin/platelet ratio > 16.08 at 2 weeks after induction therapy may have a relatively poor induction response. Ferritin/platelet ratio after induction therapy can be a good predictor for induction response in adult patients with HLH.

Repeated apheresis donations cause important iron deficiency in male Japanese donors.

BACKGROUND AND OBJECTIVES: In Japan, apheresis donation of plasma is allowed to a maximum of 24 times a year, and plateletpheresis are counted as two plasmapheresis donations. Diversion of the initial blood flow is conducted for all donations, and additionally, blood remaining in apheresis machine circuit is lost. Here, we aimed to investigate on the health impact of frequent apheresis donations, as measured by the serum ferritin (sFer). MATERIALS AND METHODS: A total of 538 male apheresis donors and 538 age-matched whole blood (WB) donors, who gave informed consent to join the study, were enrolled. sFer were compared, according to age. Another group of 19 apheresis donors were followed during four consecutive donations. RESULTS: About half (48%) of repeat male apheresis donors had iron deficiency (sFer < 26 ng/mL), compared with lower rates (13.9%) among male WB donors. It was evident in all age groups, except for teenagers, possibly because of the lower number of donations. Follow-up of the 19 donors for 4 months revealed a progressive decrease in sFer. CONCLUSION: Blood remaining in the apheresis machine circuit and diversion of the initial blood flow have been implicated in iron deficiency for many years. Taking the present results, the manufacturer of apheresis equipment was requested to improve it to allow rinseback of the remaining blood, which was achieved only for plateletpheresis. Until further improvement, plasmapheresis frequency was reduced to 12 times a year. Additional measures, such as oral supplementation of iron, need to be considered.

Iron deficiency among Japanese whole-blood donors measured by serum ferritin.

BACKGROUND AND OBJECTIVES: A more restrictive blood donation criterion has been applied in Japan, with a maximum volume of whole blood (WB) donation of 400 mL, allowing twice a year for female donors and thrice a year for male donors. However, iron deficiency was as high as 20.5% among female donors prior to donation, increasing to 37.7% after blood donation. More than 20 years have passed since then, so we set out to investigate the present situation. MATERIALS AND METHODS: A total of 2659 (male/female: 1496/1163) donors of 400 mL WB who gave informed consent to join the study were enrolled. Serum ferritin (sFer) of first-time/reactivated (FT/RA) donors were compared with those of repeat donors, according to gender and age; those who returned for subsequent donations during the study period were also followed up. RESULTS: About one-third of FT/RA female donors had iron deficiency, possibly reflecting its high incidence among the general population. Interestingly, although sFer levels were low among pre-menopausal FT/RA female donors, these values were not much different in repeat donors, whereas significant differences were observed between FT/RA and repeat donors among post-menopausal females and in most age groups among males. As expected, donors with a normal initial sFer (≥26 ng/mL) recovered faster than those with a low initial sFer. CONCLUSION: Female donors, especially, have iron deficiency even before donation, and the rate increased compared to what was found previously. Measures to prevent iron deficiency of blood donors is required, and studies are going on in Japan.

Risk prediction of iron deficiency for plasmapheresis donors in China: Development and validation of a prediction model.

BACKGROUND AND OBJECTIVES: The present study aims to evaluate the iron stores in plasmapheresis donors and develop and validate an iron deficiency (ID) risk prediction model for plasmapheresis donors with potential or existing ID. MATERIALS AND METHODS: We assessed plasmapheresis donors' serum ferritin (SF) and haemoglobin (Hb) levels. The candidate factors showing significant differences in the multivariate logistic regression analysis were used to establish a risk prediction scoring system. The participants were divided into a training cohort and an internal validation cohort in a 7:3 ratio. Additional plasmapheresis donors from a different station were recruited for external validation. RESULTS: The SF levels in both male and female donors in the high-frequency group were significantly lower than those of new donors (male: p < 0.001; female: p = 0.008). The prevalence of ID in female regular donors with a high frequency was significantly higher than that in new donors (33.1% vs. 24.6%; odds ratio = 1.209 [95% CI: 1.035-1.412]). Donation frequency, age, Hb, body mass index and being pre-menopausal were identified as independent risk factors for ID (p < 0.05). The developed model exhibited good discrimination ability (area under the receiver operating characteristic curve >0.7) and calibration (p > 0.05) in development, internal validation cohorts and external validation cohorts. CONCLUSION: A higher donation frequency has been associated with reduced SF levels and an increased risk of ID in women. The developed ID risk prediction model demonstrates moderate discriminative power and good model fitting, suggesting its potential clinical utility.

Serum ferritin and risk of colonic neoplasia: Implications for the workup and treatment of iron deficiency.

Iron deficiency is the most common extraintestinal sign of colonic neoplasia, including colorectal cancer (CRC) and other lower gastrointestinal pathology. Both upper endoscopy and colonoscopy is usually recommended in the work-up of patients with unexplained iron deficiency, particularly in men and postmenopausal women. As the incidence of early-onset CRC (age <50 years) rises in the United States, there is an increasing need to identify risk predictors to aid in the early detection of CRC. It remains unknown if serum ferritin (SF), and what specific threshold, can be used as a marker to stratify those at risk for CRC and other lower gastrointestinal pathology. In this current review of the literature, we aimed to review guidelines for diagnostic workup of colonic neoplasia in the setting of iron deficiency and examine the association and specific thresholds of SF and risk of CRC by age. Some of the published findings are conflicting, and conclusions specific to younger patients are limited. Though further investigation is warranted, the cumulative findings suggest that SF, in addition to considering the clinical context and screening guidelines, may have potential utility in the assessment of colonic neoplasia.

Serum ferritin level as a prognostic biomarker for predicting dengue disease severity: A systematic review and meta-analysis.

Serum ferritin levels serves as biomarkers in many inflammatory and infectious diseases. This current systematic review and meta-analysis evaluated whether serum ferritin levels are associated with severe dengue and its utility as a biomarker of disease severity. Literature searches were conducted in PubMed, Scopus, ScienceDirect, the Cochrane library, and Google Scholar. A total of 18 studies examining the serum ferritin levels in dengue cases in the context of disease severity (nine studies having dengue classification as non-severe vs. severe dengue cases, and nine studies having dengue classification as dengue without warning signs (DwoWS), dengue with warning signs (DwWS), and severe dengue cases) were included and the quality of the studies was assessed using the Quality in Prognostic Factor Studies tool. The meta-analysis was performed using STATA software to calculate the effect size as a standardized mean difference (SMD) or Hedges 'g' for the continuous outcome. Higher serum ferritin levels were found in severe dengue cases compared to non-severe cases [SMD (Hedges 'g') 4.05 (95% C.I. 2.09-6.00), (I2  = 98.8%)]. In the second group, DwWS cases showed high serum ferritin levels compared to DwoWS [SMD 2.01 (95% C.I. 0.92-3.10), (I2  = 97.89%)], and severe dengue cases showed higher levels of serum ferritin compared to DwWS [SMD 2.66 (95% C.I. 1.72-4.48), (I2  = 98.78%)] and DwoWS cases [SMD 6.65 (95% C.I. 1.72-11.59), (I2  = 99.78%]. Subgroup analysis for the country of study (India vs. others), ferritin testing methods, and ferritin measurement day revealed testing method as a significant contributor to heterogeneity. To conclude, the present study suggests serum ferritin as a prognostic marker for dengue disease severity. Multi-centric studies involving a large number of dengue patients with a uniform case definition accounting for all the confounding variables might help in determining a universal cut-off value to discriminate between non-severe and severe dengue.

Ferritin and iron supplements in gestational diabetes mellitus: less or more?

Iron metabolism has been found to be closely related to gestational diabetes mellitus (GDM). Excessive ferritin levels were shown to be related to an increased risk of GDM because of iron overload which may lead to insulin resistance and ß-cell injury by enhancing oxidative stress and inflammatory responses. On the contrary, insufficient ferritin levels can cause a number of obstetric complications, such as high incidence rates of anaemia and gestational hypertension. Therefore, high or low ferritin levels may have adverse effects on the mother and the foetus, putting clinicians in a dilemma when giving pregnant women iron supplements. This also explains why there have been more conflicting findings in the studies on dietary or oral iron supplementation during pregnancy. Hence, there is an urgent need for more evidence and strategies for appropriate recommendations for ferritin levels and iron supplementation during pregnancy to prevent iron insufficiency without causing iron overload and increasing the risk of GDM. Therefore, we gave an updated review on the association of GDM with ferritin metabolism, ferritin levels and iron supplementation based on the summary of the latest research.

Influence of an iron dextran injection in various diseases on hematological blood parameters, including serum ferritin, neonatal dairy calves.

BACKGROUND: Feeding milk substitutes with low iron content or whole milk without iron supplementation is considered a major factor in developing iron-deficiency anemia in neonatal dairy calves. Young calves are often supplemented with iron dextran injections on the first day of life to prevent anemia. However, the effects of preventive treatment and the presence of disease on serum iron (Fe) concentrations, serum ferritin levels, and hematological blood parameters during the early neonatal stages have not been examined in detail. Therefore, we examined and evaluated the effects of iron dextran injections and health status on the development of hematocrit (Ht), red blood cells (RBC), hemoglobin concentration (Hb), erythrocyte indices (mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration), Fe, and serum ferritin concentrations in dairy calves within the first 10 days of life. The suitability of serum ferritin as a reliable indicator of anemia in very young calves was evaluated by correlating ferritin concentrations with known laboratory diagnostic parameters of anemia. RESULTS: Iron supplementation significantly increased Fe levels (P = 0.048) but did not affect serum ferritin levels in neonatal calves. Fe concentrations were significantly lower in diseased than healthy calves (P = 0.0417). Iron supplementation significantly affected the health status, as observed in Ht (Ptreat=0.0057; Phealth=0.0097), RBC (Ptreat=0.0342; Phealth=0.0243), and Hb (Ptreat=0.0170; Phealth=0.0168). Serum ferritin levels did not significantly correlate with Fe levels. Both groups showed marked differences in ferritin levels, with the highest levels measured on day 2. Fe concentrations showed weak negative correlations with Hb and Ht levels on day 3 (ρ=-0.45; P = 0.0034 and ρ=-0.045; P = 0.0032, respectively). RBC count showed strong positive correlations with Hb and Ht levels (ρ = 0.91 and ρ = 0.93; P < 0.001). CONCLUSION: Iron dextran injections increased Fe concentrations but reduced Ht level, RBC count, and Hb level. The presence of diseases led to a reduction in Fe and higher values of Ht, RBC, and Hb in moderate disease than in severe disease. Due to physiological fluctuations during the first 3 days of life, serum ferritin level seems unuseful for evaluating iron storage before day 4 of life.

Associations between serum ferritin baselines and trajectories and the incidence of metabolic dysfunction-associated steatotic liver disease: a prospective cohort study.

BACKGROUND AND AIMS: Evidence from prospective cohort studies on the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and longitudinal changes in serum ferritin (SF) still limited. This study aimed to investigate the associations of SF baselines and trajectories with new-onset MASLD and to present a MASLD discriminant model. METHODS: A total of 1895 participants who attended health examinations at least three times in a hospital in Dalian City between 2015 and 2022 were included. The main outcome was the incidence of MASLD. The associations between SF baselines and trajectories with the risk of MASLD were analyzed by Cox proportional hazards regression, restricted cubic spline (RCS) analysis and time-dependent receiver operating characteristic (ROC) curve analysis. In addition, a MASLD discrimination model was established using logistic regression analyses. RESULTS: Among the 1895 participants, 492 developed MASLD during follow-up. Kaplan-Meier analysis indicated that participants in the low-stable trajectory group had a longer MASLD-free time compared with participants in other groups. Compared with those in the low-stable trajectory group, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of new-onset MASLD in the medium-high, high-stable and high-high trajectory groups were 1.54(1.18-2.00), 1.77(1.35-2.32) and 1.55(1.07-2.26), respectively (Ptrend < 0.001). The results were robust in subgroup and sensitivity analyses. Multivariate Cox proportional regression showed that SF was an independent risk factor of MASLD (HR = 1.002, 95%CI: 1.000-1.003, P = 0.003). The restricted cubic spline demonstrated a nonlinear relationship between SF and the risk of MASLD. The 8-variable model had high discriminative performance, good accuracy and clinical effectiveness. The ROC curve results showed that AUC was greater than that of the FLI, HSI and ZJU models (all P < 0.01). CONCLUSIONS: Not only a higher baseline SF but also SF changing trajectory are significantly associated with risk of new-onset MASLD. SF could be a predictor of the occurrence of MASLD.

Consumption Pattern of Tea Is Associated with Serum Ferritin Levels of Women of Childbearing Age in Nandi County, Kenya: A Cross-Sectional Study.

INTRODUCTION: Tea consumption with meals affects iron absorption, increasing the risk of iron deficiency. Our study investigated the association between tea consumption patterns and serum ferritin levels among women of childbearing age (WCA) in Nandi County, Kenya. METHODS: We conducted a cross-sectional analytical study among 160 WCA selected using a systematic random sampling technique from Kapsabet Ward. Information on tea consumption practices was gathered using a researcher-administered questionnaire, and serum ferritin and C-reactive protein were measured. We assessed associations between tea consumption and iron status of respondents by multivariable regression analysis, adjusting for potential confounders, including parasitic infections and recent severe blood losses. RESULTS: The prevalence of anaemia and iron deficiency among the study participants were 86.2% and 45%, respectively. Majority (90.6%) of the respondents consumed tea or coffee, with an infusion time of more than 5 min (60.0%) and a moderate tea strength (64.1%), within 1 h before or after meals. Iron deficiency was associated the number of teacups consumed (adjusted odds ratio = 7.282, 95% CI = 3.580-14.812). CONCLUSION: High tea consumption is positively associated with iron deficiency among WCA. Lower tea infusion strength, shorter tea infusion duration, and a lower number of teacups overall consumed, as well as consuming tea 1 h before or after meals instead of with meals, may be recommended for better outcomes in iron status among WCA.

Prevalence of iron deficiency in patients admitted to a geriatric unit: a multicenter cross-sectional study.

BACKGROUND: Iron deficiency (ID) is often associated with other comorbidities in older patients and is a factor of morbimortality. However, the prevalence of ID remains poorly documented in this population. METHODS: The CARENFER PA study was a French multicenter cross-sectional study whose objective was to evaluate ID in patients (> 75 years) admitted to a geriatric unit. The primary endpoint was the ID prevalence defined as: serum ferritin < 100 µg/L and/or transferrin saturation coefficient (TSAT) < 20%. The Short Physical Performance Battery (SPPB) test was used to identify older patients at high risk of adverse events (e.g., disability, falls, hospitalization, death). RESULTS: A total of 888 patients (mean age, 85.2 years; women, 63.5%) from 16 French centers were included from October 2022 to December 2022. The prevalence of ID was 57.6% (95% CI, 54.3-60.9) in the cohort of older patients (62.6% in anemic and 53.3% in non-anemic patients; p = 0.0062). ID prevalence increased significantly with the presence of more than three comorbidities (65.6% vs. 55.9%; p = 0.0274), CRP ≥ 12 mg/L (73.0% vs. 49.3%; p < 0.001) and treatment that may influence ID/anemia (60.5% vs. 49.6%; p = 0.0042). In multivariate analysis, only CRP ≥ 12 mg/L was an independent predictive factor of ID (odds ratio, 2.78; 95% CI, 1.92-4.08; p < 0.001). SPPB scores were low (0-6) in 60.5% of patients with ID versus 48.6% of patients without ID (p = 0.0076). CONCLUSION: More than half of older patients had ID, including non-anemic patients. ID was associated with the presence of inflammation and a low SPPB score. TRIAL REGISTRATION: NCT05514951.

Association between suicide attempts and anemia in late-life depression inpatients.

BACKGROUND: Anemia is strongly associated with late-life depression (LLD), however, few studies have investigated the relationship between anemia and suicide attempts in LLD patients. It is still challenging to predict suicide risk in patients with depression. Therefore, there is growing interest in potential biomarkers of depressive disorders and suicidal behavior, which may play a significant role in the early diagnosis and treatment of depression. This study aimed to compare serum ferritin, folate, vitamin B12, and erythrocyte parameter levels in patients with LLD with those in healthy older adults, and the relationship between serum ferritin, folate, vitamin B12, and suicide attempts in patients. METHODS: Serum ferritin, folate, vitamin B12, and erythrocyte parameter levels were measured in 66 hospitalized LLD patients (30 without suicide attempt, 36 with suicide attempt) and 47 healthy individuals. All participants were surveyed for basic conditions and suicide attempts, and depression was assessed in LLD patients. RESULTS: Serum ferritin, folate, vitamin B12, red blood cell count, hemoglobin, hematocrit, mean platelet volume and plateletcrit levels were significantly lower in LLD patients compared with healthy older adults (P < 0.05). Further analysis of the relationship between serum ferritin, folate, and vitamin B12 levels and LLD patients' suicide attempts and showed a significant negative association between serum folate and vitamin B12 and suicide attempts (P < 0.05). CONCLUSIONS: Serum ferritin, folate, vitamin B12, red blood cell count, hemoglobin, hematocrit, mean platelet volume and plateletcrit levels were significantly lower in LLD patients than in healthy older adults. In addition, reduced serum folate and vitamin B12 levels in patients may have some effect on suicide attempts. More mechanistic studies are needed to further explain this association.

High Ferritin Is Not Needed in Hemodialysis Patients: A Retrospective Study of Total Body Iron and Oral Iron Replacement Therapy.

In vivo iron levels can be adjusted through intestinal iron absorption to be maintained at a suitable level; however, optimal iron levels in hemodialysis (HD) patients are unclear. In this study, we investigated total body iron (TBI), calculated as the sum of red blood cell (RBC) iron and iron stores, during courses of low-dose oral iron replacement therapy, and evaluated in vivo iron sufficiency and its indicators in HD patients. We analyzed data on 105 courses of low-dose iron replacement therapy administered to 83 patients on maintenance HD over 7 months. We evaluated changes in TBI, RBC iron, and iron stores from the initiation of treatment to month 7 in two groups of patients, namely, iron-therapy responders and non-responders. TBI showed significant increases until month 4 and plateaued thereafter in iron-therapy responders, and tended to increase and then reached a similar plateau in non-responders (month 7: 1900 ± 447 vs. 1900 ± 408 mg). Steady-state TBI was strongly correlated with body surface area (y = 1628.6x - 791.91, R2 = 0.88, p < 0.001). We observed constant TBI during oral iron replacement therapy suggesting the activation of a "mucosal block". The results suggest that body surface area has utility for estimating the required TBI with regression equations.

Hemochromatosis: Ferroptosis, ROS, Gut Microbiome, and Clinical Challenges with Alcohol as Confounding Variable.

Hemochromatosis represents clinically one of the most important genetic storage diseases of the liver caused by iron overload, which is to be differentiated from hepatic iron overload due to excessive iron release from erythrocytes in patients with genetic hemolytic disorders. This disorder is under recent mechanistic discussion regarding ferroptosis, reactive oxygen species (ROS), the gut microbiome, and alcohol abuse as a risk factor, which are all topics of this review article. Triggered by released intracellular free iron from ferritin via the autophagic process of ferritinophagy, ferroptosis is involved in hemochromatosis as a specific form of iron-dependent regulated cell death. This develops in the course of mitochondrial injury associated with additional iron accumulation, followed by excessive production of ROS and lipid peroxidation. A low fecal iron content during therapeutic iron depletion reduces colonic inflammation and oxidative stress. In clinical terms, iron is an essential trace element required for human health. Humans cannot synthesize iron and must take it up from iron-containing foods and beverages. Under physiological conditions, healthy individuals allow for iron homeostasis by restricting the extent of intestinal iron depending on realistic demand, avoiding uptake of iron in excess. For this condition, the human body has no chance to adequately compensate through removal. In patients with hemochromatosis, the molecular finetuning of intestinal iron uptake is set off due to mutations in the high-FE2+ (HFE) genes that lead to a lack of hepcidin or resistance on the part of ferroportin to hepcidin binding. This is the major mechanism for the increased iron stores in the body. Hepcidin is a liver-derived peptide, which impairs the release of iron from enterocytes and macrophages by interacting with ferroportin. As a result, iron accumulates in various organs including the liver, which is severely injured and causes the clinically important hemochromatosis. This diagnosis is difficult to establish due to uncharacteristic features. Among these are asthenia, joint pain, arthritis, chondrocalcinosis, diabetes mellitus, hypopituitarism, hypogonadotropic hypogonadism, and cardiopathy. Diagnosis is initially suspected by increased serum levels of ferritin, a non-specific parameter also elevated in inflammatory diseases that must be excluded to be on the safer diagnostic side. Diagnosis is facilitated if ferritin is combined with elevated fasting transferrin saturation, genetic testing, and family screening. Various diagnostic attempts were published as algorithms. However, none of these were based on evidence or quantitative results derived from scored key features as opposed to other known complex diseases. Among these are autoimmune hepatitis (AIH) or drug-induced liver injury (DILI). For both diseases, the scored diagnostic algorithms are used in line with artificial intelligence (AI) principles to ascertain the diagnosis. The first-line therapy of hemochromatosis involves regular and life-long phlebotomy to remove iron from the blood, which improves the prognosis and may prevent the development of end-stage liver disease such as cirrhosis and hepatocellular carcinoma. Liver transplantation is rarely performed, confined to acute liver failure. In conclusion, ferroptosis, ROS, the gut microbiome, and concomitant alcohol abuse play a major contributing role in the development and clinical course of genetic hemochromatosis, which requires early diagnosis and therapy initiation through phlebotomy as a first-line treatment.

The Effects of Iron Administration on Anemia Development during the 7th and 21st Day of Life in Premature Newborns: A Prospective Cohort Study.

Background and Objectives: The administration of iron to premature newborns is a common intervention aimed at preventing iron deficiency (ID). However, there is no consensus on the optimal timing and dosage for iron supplementation in this population. This study evaluates the effects and potential adverse outcomes of administering iron on the 7th and 21st days of life in premature infants. Materials and Methods: This research was conducted on 108 premature neonates at the "Louis Turcanu" Children's Emergency Clinical Hospital in Timisoara, Romania. The study population was divided into a control group of 48 newborns who did not receive iron supplementation and an intervention group of 60 newborns who did. The analysis utilized univariate and multivariate regression to examine binary outcomes. Results: The findings indicate that iron supplementation significantly increased the risk of anemia during the premature period at 21 days of life, as demonstrated by both univariate and multivariate regression analyses, with an odds ratio (OR) of 2.40 (95% CI, 1.01-5.68) and an adjusted odds ratio (AOR) of 2.75 (95% CI, 1.06-7.11), respectively. Contrary to expectations, iron supplementation did not significantly alter the risk of abnormal serum ferritin or iron levels at 21 days of life, according to the univariate analysis (p = 0.380 and p = 0.526, respectively). Conclusions: The observed increase in the risk of anemia without a corresponding improvement in the serum ferritin or iron levels suggests the need for further investigation into alternative strategies for iron supplementation in premature newborns.

Alteration of Maternal Serum Ferritin in Pregnancy and Maternal-fetal Infections: A retrospective cohort study.

Objectives: To investigate the association of altered serum ferritin during pregnancy with chorioamnionitis and neonatal sepsis. Methods: This retrospective cohort study included 78,521 pregnant women who attended antenatal check-ups at maternal and child health centers in Fujian Province, China. Study lasted from January 2014 to January 2019. A total of 59,812 pregnant women were followed up. Patients with suspected infection before the delivery were selected and divided into the chorioamnionitis and non-chorioamnionitis groups according to placental pathology. Differences in late and early pregnancy serum ferritin between the two groups were compared. Multiple logistics regression was used to adjust for confounding factors and to analyze the association between serum ferritin changes and pregnancy outcomes. Importance of altered serum ferritin during pregnancy was assessed by receiver operating characteristic (ROC) curve and net reclassification index (NRI). Results: Clinical records of 8506 pregnant women were included in the study. there were 1010 (11.9%) cases of confirmed chorioamnionitis and 263 (3.1%) cases of neonatal sepsis. There was a significant difference in maternal serum ferritin changes between the groups with and without chorioamnionitis. No significant difference was detected in cases with or without neonatal sepsis. Multiple logistic regressions, corrected for confounding factors yielded similar conclusions. Maternal serum ferritin difference NRI 12.18% (p = 0.00014) was similar to the ROC results in predicting the occurrence of chorioamnionitis. Conclusion: Differential serum ferritin during pregnancy may predict chorioamnionitis but does not correlate well with neonatal sepsis.

Evaluating the value of superoxide dismutase in anti-MDA5-positive dermatomyositis associated with interstitial lung disease.

OBJECTIVE: This study aimed to investigate the relationship between serum superoxide dismutase (SOD) and interstitial lung disease (ILD) among patients with anti-melanoma differentiation-associated gene 5 antibody (MDA5)-positive DM. METHOD: In this retrospective study, serum SOD of 90 health check-ups were tested in our hospital. A total of 94 hospitalized patients with anti-MDA5-positive DM had ILD. Their serum SOD, serum ferritin and autoantibody levels were determined and lung high-resolution CT was performed. RESULTS: The serum SOD level was significantly lower in the anti-MDA5-positive DM group compared with the control group. The SOD level was significantly lower in patients positive for both anti-MDA5 antibodies and anti-Ro-52 antibodies than in those positive for only anti-MDA5 antibodies before treatment. The SOD level was significantly lower in the higher serum ferritin group compared with the lower serum ferritin group before treatment. After treatment, the serum SOD level decreased in patients with exacerbation of ILD, while it increased in those with alleviated ILD. The SOD level was significantly lower in the death group than in the survival group before treatment. CONCLUSIONS: In patients with anti-MDA5-positive DM, the low SOD level before treatment indicated the presence of oxidative stress in the disease; the serum SOD level was affected by anti-Ro-52 antibodies and ferritin; there is a close relationship between serum SOD level and ILD among patients with anti-MDA5-positive DM, suggesting that SOD might serve as an effective indicator to evaluate the changes in ILD in these patients; and the low SOD level is an important indicator of poor prognosis in these patients, which deserves attention from rheumatologists.